Labeling Requirements for Approved or Conditionally Approved New Animal Drugs, 18262-18337 [2024-04840]
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Federal Register / Vol. 89, No. 49 / Tuesday, March 12, 2024 / Proposed Rules
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must include the Docket No. FDA–
2023–N–5160 for ‘‘Labeling
Requirements for Approved or
Conditionally Approved New Animal
Drugs.’’ Received comments, those filed
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Food and Drug Administration
21 CFR Parts 201, 500, 501, 510, 514,
and 516
[Docket No. FDA–2023–N–5160]
RIN 0910–AI43
Labeling Requirements for Approved
or Conditionally Approved New Animal
Drugs
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Proposed rule.
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The Food and Drug
Administration (FDA) is proposing to
revise the requirements for the content
and format of labeling for approved or
conditionally approved new animal
drugs to provide for a more
comprehensive set of requirements in
one location in the Code of the Federal
Register (CFR). As part of this revision,
certain current requirements would be
updated and moved, and certain
obsolete requirements would be
removed. The proposed requirements
would apply to the labeling of
prescription and over-the-counter (OTC)
new animal drugs, as well as new
animal drugs for use in animal feeds.
DATES: Either electronic or written
comments on the proposed rule must be
submitted by June 10, 2024. Submit
written comments (including
recommendations) on information
collection issues under the Paperwork
Reduction Act of 1995 by April 11,
2024.
ADDRESSES: You may submit comments
as follows. Please note that late,
untimely filed comments will not be
considered. The https://
www.regulations.gov electronic filing
system will accept comments until
11:59 p.m. Eastern Time at the end of
June 10, 2024. Comments received by
mail/hand delivery/courier (for written/
paper submissions) will be considered
timely if they are received on or before
that date.
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Staff. If you do not wish your name and
contact information to be made publicly
available, you can provide this
information on the cover sheet and not
in the body of your comments and you
must identify this information as
‘‘confidential.’’ Any information marked
as ‘‘confidential’’ will not be disclosed
except in accordance with 21 CFR 10.20
and other applicable disclosure law. For
more information about FDA’s posting
of comments to public dockets, see 80
FR 56469, September 18, 2015, or access
the information at: https://
www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf.
Docket: For access to the docket to
read background documents, the plain
language summary of the proposed rule
of not more than 100 words are required
by the ‘‘Providing Accountability
Through Transparency Act,’’ or the
electronic and written/paper comments
received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852.
Submit comments on information
collection issues under the Paperwork
Reduction Act of 1995 to the Office of
Management and Budget (OMB) https://
www.reginfo.gov/public/do/PRAMain.
Find this particular information
collection by selecting ‘‘Currently under
Review—Open for Public Comments’’ or
by using the search function. The title
of this proposed collection is ‘‘Labeling
Requirements for Approved or
Conditionally Approved New Animal
Drugs.’’
FOR FURTHER INFORMATION CONTACT:
With regard to the proposed rule:
Suzanne Sechen, Center for Veterinary
Medicine, Food and Drug
Administration, 7500 Standish Pl.,
Rockville, MD 20855, 240–402–0814,
Suzanne.Sechen@fda.hhs.gov.
With regard to the information
collection: Amber Sanford, Office of
Operations, Food and Drug
Administration, Three White Flint
North, 10A–12M, 11601 Landsdown St.,
North Bethesda, MD 20852, 301–796–
8867, PRAStaff@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose and Coverage of the Proposed
Rule
B. Summary of the Major Provisions of the
Proposed Rule
C. Legal Authority
D. Costs and Benefits
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II. Table of Abbreviations/Commonly Used
Acronyms in This Document
III. Background
A. Introduction
B. Need for the Regulation
C. FDA’s Current Regulatory Framework
D. History of the Rulemaking
IV. Legal Authority
V. Description of the Proposed Rule
A. Scope (Proposed § 201.401)
B. Definitions (Proposed § 201.403)
C. General Requirements (Proposed
§ 201.404)
D. Content and Format for Prescription
(Rx) New Animal Drug Labeling—
Overview (Proposed § 201.405)
E. Content and Format for Over-TheCounter (OTC) New Animal Drug
Labeling—Overview (Proposed
§ 201.407)
F. Content and Format of Labeling for New
Animal Drugs for Use in Animal Feeds—
Overview (Proposed § 201.409)
G. Exemptions From Labeling
Requirements for Approved or
Conditionally Approved New Animal
Drugs (Proposed § 201.411)
H. Labeling Requirements for Certain
Approved or Conditionally Approved
New Animal Drugs (Proposed § 201.413)
I. Proposed Conforming Amendments
VI. Proposed Effective/Compliance Dates
VII. Preliminary Economic Analysis of
Impacts
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Consultation and Coordination With
Indian Tribal Governments
XII. References
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I. Executive Summary
A. Purpose and Coverage of the
Proposed Rule
FDA proposes to revise the existing
regulations regarding the content and
format of labeling for approved or
conditionally approved new animal
drugs. These proposed regulations
would apply to the labeling of
prescription and OTC new animal
drugs, as well as new animal drugs for
use in animal feeds. Certain existing
regulations regarding the labeling of
new animal drugs would be updated
and moved from their current location
and incorporated into the proposed
regulations, including a new subpart H
in part 201 (21 CFR part 201). FDA also
proposes to amend or remove certain
current regulations to ensure
consistency with the proposed
regulations.
Proposed subpart H would not apply
to heritable intentional genomic
alterations in animals. Proposed subpart
H would also not apply to labeling of
indexed legally marketed unapproved
new animal drugs for minor species. In
addition, proposed subpart H would not
apply to promotional labeling or
advertising.
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B. Summary of the Major Provisions of
the Proposed Rule
The proposed rule would revise the
existing requirements for the content
and format of labeling for approved or
conditionally approved new animal
drugs. If finalized, sponsors of these
new animal drugs would need to
comply with these proposed regulations
on a staggered schedule, over the course
of 6 years, according to a schedule based
on application number, with approved
NADAs with higher application
numbers having the earliest compliance
date because they are more recently
approved and therefore likely to need
the fewest labeling revisions.
If finalized, this rule would enable
FDA to provide sponsors with
predictable requirements for the content
and format of labeling for new animal
drugs and codify FDA’s longstanding
practices with respect to the review of
labeling submitted as part of a new
animal drug application (NADA),
certain abbreviated new animal drug
applications (ANADAs) that reference a
new animal drug for which the NADA
has been withdrawn, or a new animal
drug application for conditional
approval (CNADA).
Currently a comprehensive set of
regulations establishing labeling
requirements for the content and format
of labeling for new animal drugs does
not exist in the CFR. These proposed
regulations would provide sponsors
with predictable requirements for the
content and format of labeling for new
animal drugs. Also, these proposed
regulations would help sponsors more
efficiently prepare labeling for new
animal drugs to be submitted as part of
an NADA, CNADA, or certain ANADAs
by providing clear and consistent
requirements for the information that
would need to be included on each
component of labeling for a new animal
drug, as well as the format in which the
information is to be presented.
FDA is proposing specific
requirements for content and format of
the labeling for approved or
conditionally approved prescription and
OTC new animal drugs, as well as
approved or conditionally approved
new animal drugs for use in animal
feeds.
The proposed regulations would
provide the following:
• The content and format of labeling
components applicable to approved or
conditionally approved new animal
drugs.
• Definitions of labeling terms for
approved or conditionally approved
new animal drugs.
• A schedule for sponsors of
approved or conditionally approved and
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marketed new animal drugs to comply
with these proposed regulations within
a maximum of 6 years from the effective
date of any final rule.
• Provisions for foreign language
translation of the labeling for approved
or conditionally approved new animal
drugs.
• A process for sponsors of new
animal drugs to request exemptions
from the proposed labeling
requirements.
• Consolidation of the labeling
requirements for the content and format
of labeling for approved or conditionally
approved new animal drugs into one
section of the regulations. At present,
existing requirements are dispersed
throughout the regulations.
C. Legal Authority
FDA’s revisions to the content and
format requirements for animal drug
labeling are authorized by various
provisions of the Federal Food, Drug,
and Cosmetic Act (FD&C Act). The
premarket approval provisions of the
FD&C Act authorize FDA to require that
new animal drug labeling provide
adequate information to permit safe and
effective use of the drug.
The FD&C Act requires certain
information be included on a drug’s
label and provides for certain
exemptions from these requirements.
Also, the FD&C Act authorizes FDA to
establish additional exemptions by
regulation.
The FD&C Act requires that new
animal drug applications include
specimens of the labeling proposed to
be used for the drug. A new animal drug
will be deemed unsafe if its labeling
fails to conform to the approved labeling
in the applicable approved new animal
drug application, conditionally
approved new animal drug application,
or new animal drug index listing.
Unsafe drugs are deemed adulterated
under the provisions of the FD&C Act.
The FD&C Act prohibits the marketing
of drugs that are adulterated or
misbranded as well as their adulteration
or misbranding while in interstate
commerce.
In addition to the other statutory
provisions described above, the FD&C
Act gives the FDA general rulemaking
authority to issue regulations for the
efficient enforcement of the FD&C Act.
D. Costs and Benefits
If this proposed rule is finalized,
industry and FDA would incur cost
savings from a reduction in the quantity
and time burden of new animal drug
labeling amendments and informal
communications related to new animal
drug labeling. There may be additional
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benefits to users of approved or
conditionally approved new animal
drugs from greater predictability and
ease of reading new animal drug
labeling in the form of time saved
searching for content, as well as benefits
to animal or human health, which we
are unable to quantify.
We expect that new animal drug
sponsors would incur one-time costs to
read and understand the rule, revise
standard operating procedures (SOPs)
related to labeling, and train employees
on the revised SOPs. New animal drug
sponsors would also bear costs to
update labeling and prepare
supplemental labeling applications to
conform to the proposed requirements.
FDA would incur costs to review these
supplemental applications.
FDA estimates that the annualized
benefits over 10 years would range from
Abbreviation/acronym
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III. Background
A. Introduction
In accordance with the definition in
section 201(k) of the FD&C Act (21
U.S.C. 321(k)) the ‘‘label’’ is a display of
written, printed, or graphic matter upon
the immediate container of any article.
Under section 201(m) of the FD&C Act,
the term ‘‘labeling’’ means ‘‘all labels
and other written, printed, or graphic
matter (1) upon any article or any of its
containers or wrappers, or (2)
accompanying such article.’’ Labeling,
therefore, includes the label of any
article, including new animal drugs.
Under existing regulations, proposed
labeling must be included as part of an
application filed with FDA for approval
of a new animal drug, in accordance
with section 512(b)(1)(F) of the FD&C
Act (21 U.S.C. 360b(b)(1)(F)). Labeling
for nonprescription, known as over-thecounter (OTC), new animal drugs
should include adequate directions for
use by the layperson under all
conditions of use for which the new
animal drug is intended, recommended,
or suggested in any of the labeling or
advertising sponsored by the applicant
(see § 514.1(b)(3)(ii) (21 CFR
514.1(b)(3)(ii)). Labeling for prescription
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II. Table of Abbreviations/Commonly
Used Acronyms in This Document
What it means
ADAA ...............................................................................
ANADA ............................................................................
CFR .................................................................................
CNADA ............................................................................
FD&C Act ........................................................................
FDA .................................................................................
FR ....................................................................................
HHS .................................................................................
INAD ................................................................................
MUMS ..............................................................................
NADA ...............................................................................
NDC .................................................................................
NEPA ...............................................................................
OMB ................................................................................
OTC .................................................................................
PCBs ...............................................................................
PRA .................................................................................
RLNAD ............................................................................
Rx ....................................................................................
U.S. ..................................................................................
U.S.C. ..............................................................................
VFD .................................................................................
VMF .................................................................................
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$0.143 million to $0.243 million at a 2
percent discount rate, with a primary
estimate of $0.193 million. The
annualized costs would range from
$2.16 million to $2.77 million at a 2
percent discount rate, with a primary
estimate of $2.45 million.
Animal Drug Availability Act.
Abbreviated New Animal Drug Application
Code of Federal Regulations.
Conditionally Approved New Animal Drug Application.
Federal Food, Drug, and Cosmetic Act.
Food and Drug Administration.
Federal Register.
Health and Human Services.
Investigational New Animal Drug.
Minor Use Minor Species.
New Animal Drug Application.
National Drug Code.
National Environmental Policy Act.
Office of Management and Budget.
Over-the-counter.
Polychlorinated biphenyls.
Paperwork Reduction Act of 1995.
Reference-Listed New Animal Drug.
Prescription.
United States.
United States Code.
Veterinary Feed Directive.
Veterinary Master File.
new animal drugs should bear adequate
information for use under which
veterinarians can use the new animal
drug safely and for the purposes for
which it is intended, including those
purposes for which it is to be advertised
or represented, in accordance with
§ 201.105 (21 CFR 201.105) (see
§ 514.1(b)(3)(iii)). All labeling for
prescription or OTC new animal drugs
must provide any necessary use
restrictions prominently and
conspicuously displayed (see
§ 514.1(b)(3)(iv)).
Labeling for new animal drugs
intended for use in the manufacture of
medicated feeds must include: (1)
specimens of labeling to be used for
such new animal drug with adequate
directions for the manufacture and use
of finished feeds for all conditions for
which the new animal drug is intended,
recommended, or suggested in any of
the labeling, including advertising,
sponsored by the applicant; and (2)
representative labeling proposed to be
used for Type B and Type C medicated
feeds containing the new animal drug
(see § 514.1(b)(3)(v)). Sponsors of new
animal drug applications commit to
providing labeling for the new animal
drug that prescribes, recommends, or
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suggests its use only under the
conditions stated in the labeling
included as part of the application (see
§ 514.1(b)(11)). All representations of
labeling in the application apply to the
new animal drug produced until
changes are made in conformity with
§ 514.8 (21 CFR 514.8) (see
§ 514.1(b)(11)).
Sponsors of new animal drug
applications may submit draft labeling
for FDA’s preliminary consideration of
an application (see § 514.1(b)(3)(vi)). For
example, sponsors sometimes include
draft labeling content pertinent to key
components of an application that are
submitted for preliminary FDA review
(e.g., manufacturing components and
composition, evidence to establish
safety and effectiveness, and
environmental assessment).
Under section 502(a)(1) of the FD&C
Act (21 U.S.C. 352(a)(1)), a drug shall be
deemed to be misbranded if its labeling
is false or misleading in any particular.
A new animal drug for which an
approval or conditional approval is in
effect will be considered unsafe if its
labeling fails to conform to the approved
or conditionally approved application
(section 512(a)(1)(A) and (B) of the
FD&C Act).
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B. Need for the Regulation
Based on FDA’s experience in
reviewing labeling for approved or
conditionally approved prescription
new animal drugs and informal
feedback from sponsors of such new
animal drugs in the past 60 years, it has
become clear that sponsors would
benefit from having more detailed
requirements on the content, format,
and order of information on labeling so
that they can efficiently prepare
adequate labeling for approved or
conditionally approved prescription
new animal drugs to be submitted as
part of an NADA, CNADA, or certain
ANADAs that reference a new animal
drug for which the NADA has been
withdrawn.
For example, existing § 201.105(c)
provides requirements for labeling ‘‘on
or within the package’’ from which
prescription animal drugs are
dispensed, and paragraph (d) of that
section provides requirements for all
labeling for prescription new animal
drugs. Labeling for prescription new
animal drugs typically consists of
multiple components, such as the label,
one or more package inserts, secondary
container labeling, multiple unit carton
labeling, shipping labeling, and/or
display carton labeling. However,
neither paragraph (c) nor (d) of
§ 201.105 provides direction on the
format or order of information with
respect to specific labeling components.
Furthermore, it is not clear whether the
information required by paragraph (d) of
§ 201.105 needs to be presented on all
components of labeling for prescription
new animal drugs, or if not, what
critical information needs to be
provided on specific labeling
components, particularly smaller
components of limited size.
Whereas existing § 201.105 provides
at least some requirements for the
content of labeling for prescription new
animal drugs, there are currently no
regulations that provide requirements
for the general content and format of
labeling for OTC new animal drugs and
new animal drugs administered in
animal feeds.
The lack of direction regarding format
and content for each component of
labeling has resulted in confusion for
sponsors as they prepare labeling for
FDA’s review and sometimes results in
poor quality labeling submissions. Poor
quality labeling submissions increase
the time needed by sponsors to revise
and resubmit adequate labeling, and
they increase time needed by FDA to
review and approve labeling, and
consequently, the application.
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New animal drug labeling that
presents information in an inconsistent
manner can contribute to medication
errors by making it difficult for
veterinarians and animal owners to
readily locate and understand critical
directions and safety information.
Information in the labeling for approved
or conditionally approved new animal
drugs presented in a consistent manner
communicates information that is
important to the safe use of a new
animal drug in the medication use
process (i.e., from prescription, to
procurement, preparation, and
dispensing and administration of the
medication to the animal).
Other regulations specifically
pertaining to the labeling of certain new
animal drugs include § 500.25 (21 CFR
500.25), ‘‘Anthelmintic drugs for use in
animals,’’ § 500.55 (21 CFR 500.55),
‘‘Exemption from certain drug-labeling
requirements,’’ § 510.105 (21 CFR
510.105), ‘‘Labeling of drugs for use in
milk-producing animals,’’ § 510.106 (21
CFR 510.106), ‘‘Labeling of antibiotic
and antibiotic-containing drugs
intended for use in milk-producing
animals,’’ and § 510.410 (21 CFR
510.410), ‘‘Corticosteroids for oral,
injectable, and ophthalmic use in
animals; warnings and labeling
requirements.’’
The proposed rule would locate the
labeling requirements for ‘‘Anthelmintic
drugs for use in animals,’’ currently in
§ 500.25, with other labeling
requirements for new animal drugs.
The proposed rule would remove the
exemption in § 500.55, ‘‘Exemption
from certain drug-labeling
requirements,’’ because we believe that
full disclosure labeling is needed for all
prescription new animal drugs to ensure
veterinarians are able to use these
products safely and effectively.
In addition, the proposed rule would
remove the labeling requirements in
§ 510.105, ‘‘Labeling of drugs for use in
milk-producing animals,’’ and
§ 510.106, ‘‘Labeling of antibiotic and
antibiotic-containing drugs intended for
use in milk-producing animals.’’ The
labeling requirements in these
regulations do not provide adequate
flexibility for targeted and informative
statements with respect to human food
safety warnings, including milk discard
times, withdrawal periods, and residue
warning statements for the labeling of
new animal drugs intended for use in
milk-producing animals.
Section 510.410, ‘‘Corticosteroids for
oral, injectable, and ophthalmic use in
animals; warnings and labeling
requirements,’’ contains background
information and warning and labeling
requirements for this category of new
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animal drugs. We propose a conforming
amendment to remove § 510.410 and to
move portions of that section to be
located with the other labeling
requirements for new animal drugs.
C. FDA’s Current Regulatory Framework
Current § 201.105 provides conditions
that must be met for exempting
prescription animal drugs from section
502(f)(1) of the FD&C Act, which
requires the labeling to bear adequate
directions for use. Section 201.105(b)
requires the following information to
appear on the label for prescription
animal drugs for such products to be
exempt from section 502(f)(1) of the
FD&C Act:
• a standard statement restricting use
to or on the order of a licensed
veterinarian,
• dosage,
• route of administration if it is not
oral,
• quantity or proportion of each
active ingredient as well as information
required, in accordance with section
502(e) of the FD&C Act,
• names of inactive ingredients if the
drug is for other than oral use (with
some exemptions), and
• an identifying lot or control
number.
For containers too small or otherwise
unable to fit a label with enough space
to display all the required information,
§ 201.105(b) allows eliminating some
information from these labels and
placing it on other approved labeling.
Labeling for prescription new animal
drugs must bear adequate information
for use, including indications, effects,
dosages, routes, methods, and frequency
and duration of administration; any
relevant warnings, hazards,
contraindications, side effects, and
precautions under which veterinarians
can use the drug safely and for the
intended purposes; and ingredient
information as required for the label (see
§ 201.105(c) through (e)). All
prescription animal drug labeling,
except for labels and cartons, must bear
the issuance dates of the latest revisions
of such labeling (see § 201.105(e)).
Applicants may submit a written
request to the Commissioner of Food
and Drugs for an exemption from
inclusion of adequate information for
use required in § 201.105(c)(1) from the
dispensing package of prescription new
animal drugs for which directions,
hazards, warnings, and use information
are commonly known to licensed
veterinarians (see § 201.105(c)(2)).
A prescription drug intended for both
human and veterinary use must comply
with paragraphs (e) and (f) of § 201.105,
in addition to § 201.100, which provides
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requirements for prescription drugs for
human use (see § 201.105(f)).
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D. History of the Rulemaking
In 1955, FDA issued regulations at
§ 1.106(c) establishing requirements
primarily for the label of prescription
animal drugs (20 FR 9525 at 9533,
December 20, 1955). The initial
requirements were expanded in 1960 to
cover the labeling of such drugs more
fully (25 FR 12592, December 9, 1960).
As part of FDA’s reorganization of its
regulations, in 1975 § 1.106(c) was
redesignated as § 201.105 (40 FR 13494
at 13496, March 27, 1975). Most
provisions in current § 201.105 are
similar to the 1960 version of § 1.106(c).
IV. Legal Authority
FDA’s revisions to the content and
format requirements for animal drug
labeling are authorized by various
provisions of the FD&C Act, including
sections 201, 301, 501, 502, 503, 504,
512, 571, and 701 (21 U.S.C. 321, 331,
351, 352, 353, 354, 360b, 360ccc, and
371). Section 201 contains definitions
relevant to the proposed content and
format requirements, including for the
terms ‘‘label’’ and ‘‘labeling’’. Pursuant
to section 201(k) of the FD&C Act, the
term ‘‘label’’ means ‘‘a display of
written, printed, or graphic matter upon
the immediate container of any article.’’
That provision requires that any words,
statements, or other information
appearing on the label also appear on
the outside container or wrapper of the
retail package, or be easily legible
through the outside container or
wrapper. Section 201(m) of the FD&C
Act defines ‘‘labeling’’ to mean ‘‘all
labels and other written, printed, or
graphic matter (1) upon any article or
any of its containers or wrappers, or (2)
accompanying such article.’’
Section 301 of the FD&C Act prohibits
the marketing of drugs that are
adulterated or misbranded as well as
their adulteration or misbranding while
in interstate commerce. Section
501(a)(5) of the FD&C Act deems a new
animal drug to be adulterated if it is
unsafe within the meaning of section
512 of the FD&C Act. Under section 512
of the FD&C Act, a new animal drug will
be deemed unsafe if its labeling fails to
conform to the applicable approved
application under section 512 of the
FD&C Act, conditionally approved
application under section 571 of the
FD&C Act, or index listing under section
572 of the FD&C Act (21 U.S.C. 360ccc1).
Section 502 of the FD&C Act specifies
conditions that cause a drug to be
misbranded. Under section 502(a) of the
FD&C Act, a drug is deemed to be
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misbranded if its labeling is false or
misleading ‘‘in any particular.’’ Section
201(n) of the FD&C Act deems a
product’s labeling misleading if it fails
to reveal facts regarding the
consequences that may result from
using the article under the conditions of
use prescribed in the labeling or under
such conditions of use as are customary
or usual. Under section 502(b) of the
FD&C Act, a drug in package form is
deemed to be misbranded unless its
label bears the name and place of
business of the manufacturer, packer, or
distributor, and it contains an accurate
statement of the quantity of the contents
in terms of weight, measure, or
numerical count. Section 502(c) of the
FD&C Act, deems a drug misbranded if
any word, statement, or other
information required by law or
regulation to be included on the label or
labeling does not appear with such
prominence and conspicuousness, and
in such terms, that it is likely to be read
and understood by ordinary individuals
under customary conditions of purchase
and use.
Section 502(e) of the FD&C Act
specifies requirements for including the
established name of the drug and for
listing the active and inactive
ingredients on the drug’s label. It also
provides for certain exemptions from
the requirement to list active and
inactive ingredients and authorizes the
Secretary to establish additional
exemptions from some of the
requirements in section 502(e) by
promulgating regulations where
compliance would be impracticable.
Section 502(f) of the FD&C Act deems
a drug to be misbranded if its labeling
lacks adequate directions for use and
adequate warnings against use in those
pathological conditions where its use
may be dangerous to health, as well as
adequate warnings against unsafe
dosage or methods or duration of
administration or application, in such
manner and form, as are necessary for
the protection of users.
Section 502(j) of the FD&C Act deems
a drug to be misbranded if it is
dangerous to health when used in the
dosage or manner, or with the frequency
or duration, prescribed, recommended,
or suggested in its labeling.
Under section 502(w)(1) of the FD&C
Act, a new animal drug that has been
conditionally approved is deemed to be
misbranded if its labeling fails to
conform with the approved application
or fails to include the labeling
information required under section
571(f) of the FD&C Act. Section 571(f)
requires the label and labeling of a new
animal drug with a conditional approval
to contain the statement ‘‘conditionally
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approved by FDA pending a full
demonstration of effectiveness under
application number,’’ in addition to
other information as required by the
Secretary. Effective September 30, 2023,
section 502(w)(3) requires the labeling
of new animal drugs that have received
approval under section 512 of the FD&C
Act to include the application number
in the format ‘‘Approved by FDA under
(A)NADA # xxx-xxx.’’
Section 503(f) of the FD&C Act
provides certain labeling requirements
specific to prescription animal drugs,
including a required cautionary
statement. Section 503(f)(2) exempts
prescription animal drugs from having
to comply with some of the
requirements in section 502 of the FD&C
Act, including the requirement for there
to be adequate directions for use
(section 502(f)), provided certain
dispensing and labeling requirements
specified in section 503(f) are met.
Section 504 of the FD&C Act
authorizes the Secretary to issue
regulations specific to veterinary feed
directive (VFD) drugs for use in or on
animal feed, including regulations
prescribing a cautionary statement and
other information to be included on the
labeling of VFD drugs and animal feed
containing such drugs. Under section
504(b), VFD drugs and feed containing
such drugs will be deemed to be
misbranded if their labeling fails to
include such required information.
In addition, the premarket approval
provisions of the FD&C Act authorize
FDA to require that animal drug labeling
provide adequate information to permit
safe and effective use of the drug. Under
section 512 of the FD&C Act, FDA will
approve a NADA only if the drug is
shown to be both safe and effective
under the conditions of use set forth in
the drug’s labeling. Under section 571 of
the FD&C Act, FDA will conditionally
approve a new animal drug application
(CNADA) only if the drug is shown to
be safe, and there is a reasonable
expectation of effectiveness for use,
under the conditions of use set forth in
the drug’s labeling. Section 512(b)(1)(F)
of the FD&C Act requires that the
application for approval of a new
animal drug include specimens of the
labeling proposed to be used for the
drug. A new animal drug that has been
approved or conditionally approved by
FDA will be deemed to be unsafe (and
therefore adulterated under section
501(a)(5) of the FD&C Act) if its labeling
does not conform to its approved
application.
In addition to the other statutory
provisions described above, section
701(a) of the FD&C Act gives the
Secretary general rulemaking authority
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to issue regulations for the efficient
enforcement of the FD&C Act.
FDA has previously issued
implementing regulations governing the
format and content of labeling for
animal drugs. This proposed rule, when
finalized, would revise the content and
format of labeling requirements
applicable to approved and
conditionally approved new animal
drugs and would consolidate these
requirements in subpart H of part 201.
V. Description of the Proposed Rule
FDA proposes to add subpart H to
part 201 (hereafter called proposed
subpart H) to revise the existing
requirements for the content and format
of labeling for approved or conditionally
approved new animal drugs. Proposed
subpart H would be titled ‘‘Labeling
Requirements for Approved or
Conditionally Approved New Animal
Drugs’’ and would apply to new animal
drugs that are approved under section
512 of the FD&C Act or conditionally
approved under section 571 of the FD&C
Act. These regulations would not apply
to legally marketed unapproved new
animal drugs for minor species that are
indexed in accordance with section 572
of the FD&C Act. These regulations
would not apply to the labeling of
heritable intentional genomic alterations
in animals, or to promotional labeling or
advertising.
Sponsors of approved or conditionally
approved and marketed new animal
drugs would need to comply with these
requirements per the schedule in
proposed § 201.404(a)(4), (b), (c), or (d).
Consistent with current practice, we
expect that sponsors of new animal
drugs that are the subject of an ANADA
approved or submitted pursuant to
section 512(n) of the FD&C Act (i.e., a
generic new animal drug) will submit a
supplemental application to their
ANADA to conform the labeling of their
generic new animal drugs with the
revised labeling of the reference-listed
new animal drug (RLNAD). Therefore,
in the preliminary regulatory impact
analysis we examine the costs and
benefits of these requirements for
ANADAs that reference an NADA that
has not been withdrawn. However, for
generic new animal drugs that are the
subject of an ANADA that reference a
new animal drug for which the NADA
has been voluntarily withdrawn for
reasons other than safety or
effectiveness, or that reference a new
animal drug for which the NADA that
has been withdrawn on the basis of one
or more of the grounds included under
section 512(e) of FD&C Act and for
which the ANADA’s approval was not
affected by the withdrawal, labeling for
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such ANADAs would need to comply
with proposed subpart H per the
proposed schedule described in
proposed § 201.404(a)(4)(iii).
The proposed requirements are based
on FDA’s experience in reviewing
labeling submitted for the approval or
conditional approval of new animal
drugs and its experience in
implementing existing regulations for
labeling of new animal drugs, as well as
input received from new animal drug
sponsors, end users of animal drugs,
information collected from post
approval surveillance, and other
stakeholders. We intend for these
proposed regulations to provide
consistent formatting of new animal
drug labeling by identifying the specific
labeling components that would be
required and permitted for each new
animal drug, the information needed for
each component, and the order in which
information would appear on labeling.
Consistent and standardized content
and format of new animal drug labeling
may make it easier for end users
(veterinarians, animal owners, or
persons treating the animals) to access,
read, and use the information to make
informed decisions quickly, while
promoting safe use of the drug. Such
labeling may contribute to reducing
medication errors.
Providing clear and consistent
requirements in these proposed
regulations should help to reduce the
amount of time needed by sponsors of
new animal drugs to prepare high
quality proposed labeling for their new
animal drugs. The submission of higher
quality proposed labeling by sponsors of
new animal drugs may reduce the
amount of time needed by FDA to
review and approve labeling, and
consequently, the new animal drug
application.
We include the following eight
sections in proposed subpart H:
• § 201.401 Scope.
• § 201.403 Definitions.
• § 201.404 General requirements.
• § 201.405 Content and format for
prescription new animal drug labeling.
• § 201.407 Content and format for
OTC new animal drug labeling.
• § 201.409 Content and format of
labeling for new animal drugs for use in
animal feeds.
• § 201.411 Exemptions from labeling
requirements for approved or
conditionally approved new animal
drugs.
• § 201.413 Labeling requirements for
certain approved or conditionally
approved new animal drugs.
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A. Scope (Proposed § 201.401)
The proposed rule would revise the
existing requirements for the content
and format of labeling for prescription
(Rx) new animal drugs, OTC new
animal drugs other than those for use in
animal feeds in accordance with part
558 (21 CFR part 558), and new animal
drugs for use in animal feeds that are
subject to part 558, including VFD
drugs, that are subject of the specific
applications identified in proposed
§ 201.401(a)(1) through (4).
Subpart H would apply to the labeling
of new animal drugs that are the subject
of an NADA approved or submitted
pursuant to section 512 of the FD&C Act
(see proposed § 201.401(a)(1)), new
animal drugs that are the subject of a
CNADA conditionally approved or
submitted pursuant to section 571 of the
FD&C Act (see proposed
§ 201.401(a)(2)), and new animal drugs
that are the subject of an ANADA
approved or submitted pursuant to
section 512(n) of the FD&C Act (i.e., a
generic new animal drug) that reference
a new animal drug for which the NADA
has been voluntarily withdrawn for
reasons other than safety or
effectiveness, or that reference a new
animal drug for which the NADA has
been withdrawn on the basis of one or
more of the grounds included under
section 512(e) of the FD&C Act and for
which the generic new animal drug’s
approval was not affected by the
withdrawal (see proposed
§ 201.401(a)(3)).
For some proprietary Type B or Type
C medicated feeds, the formulation and
labeling are approved and maintained in
an NADA or CNADA file. In other
situations, the underlying data and
labeling for the proprietary Type B or
Type C medicated feed to support the
approved uses are maintained in a
Veterinary Master File (VMF). The latter
would include, as an example,
situations in which a proprietary Type
B or Type C medicated feed is
manufactured via modification to an
approved formulation published in the
CFR or where a feed manufacturer
creates its own proprietary formulation.
The labeling of these proprietary
medicated feeds is maintained in a VMF
and would be required to comply with
proposed subpart H (see proposed
§ 201.401(a)(4)).
The proposed requirements would
apply to the applications described in
proposed § 201.401(a)(1) through (4) for
new animal drugs that are approved
before the effective date of any final rule
based on this proposed rule, pending on
the effective date of any final rule based
on this proposed rule, or submitted on
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or after the effective date of any final
rule based on this proposed rule (see
proposed § 201.401(c)). The schedule for
compliance is provided in proposed
§ 201.404(a)(4).
The proposed requirements would
deem any approved or conditionally
approved new animal drug subject to
this subpart that does not fully comply
with the applicable requirements in
accordance with the schedule proposed
in § 201.404(a)(4) to be misbranded
under section 502 of the FD&C Act and,
if that drug is a VFD drug, also under
section 504(b) of the FD&C Act (see
proposed § 201.401(c)).
The proposed requirements would not
apply to the labeling of legally marketed
unapproved new animal drugs for minor
species that are indexed in accordance
with section 572 of the FD&C Act (see
proposed § 201.401(d)(1)) or to the
labeling of heritable intentional genomic
alterations in animals (see proposed
§ 201.401(d)(2)).
The proposed requirements would not
apply to promotional labeling or
advertising (see proposed
§ 201.401(d)(3)). Promotional labeling
for new animal drugs is generally any
labeling other than labeling required in
an application for a new animal drug
(see § 514.1(b)(3)). Materials that may be
considered promotional labeling or
advertising include, for example,
brochures, booklets, mailing pieces, or
reminder labeling. These materials are
described in more detail for prescription
human drugs and prescription new
animal drugs in existing 21 CFR 202.1.
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B. Definitions (Proposed § 201.403)
Proposed § 201.403 would establish
definitions for terms used in proposed
subpart H.
The proposed definitions for the
following terms would be the same as
those already in the FD&C Act or
elsewhere in the regulations:
• ‘‘active ingredient’’
• ‘‘adverse drug experience’’
• ‘‘ANADA’’
• ‘‘drug product’’
• ‘‘established name’’
• ‘‘extralabel use’’
• ‘‘free-choice medicated feed’’
• ‘‘inactive ingredient’’
• ‘‘label’’
• ‘‘labeling’’
• ‘‘lot number’’
• ‘‘control number’’
• ‘‘batch number’’
• ‘‘NADA’’
• ‘‘new animal drug’’
• ‘‘sponsor’’
• ‘‘strength’’
• ‘‘Type A medicated article’’
• ‘‘Type B medicated feed’’
• ‘‘Type C medicated feed’’
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• ‘‘veterinary feed directive (VFD)’’
• ‘‘VFD drug’’
We would base the definition of ‘‘full
prescribing information’’ for
prescription new animal drugs on the
requirements for full prescribing
information for prescription human
drugs and biologics established in
§ 201.57(c) (21 CFR 201.57(c)).
For OTC new animal drugs, we would
create a similar term, called ‘‘full
product information.’’ We would define
‘‘full product information’’ as all
information necessary for the safe and
effective use of an OTC new animal
drug.
We would base the definitions of
other terms on the requirements
established in § 201.57(c) for full
prescribing information of prescription
human drugs and biologics. These terms
include ‘‘adverse reaction,’’ ‘‘boxed
warning,’’ and ‘‘contraindication.’’ The
proposed definition of ‘‘precaution’’
would be based on the requirements for
the ‘‘Other special care precautions’’
labeling section described in
§ 201.57(c)(6)(ii). The proposed
definition of ‘‘warning’’ would be based
on general requirements for the
‘‘Warnings and Precautions’’ section
described in § 201.57(c)(6)(i).
We would define ‘‘active moiety’’ as
the molecule or ion, excluding those
appended portions of the molecule that
cause the drug to be an ester, salt
(including a salt with hydrogen or
coordination bonds), or other
noncovalent derivative (such as a
complex, chelate, or clathrate) of the
molecule, responsible for the
physiological or pharmacological action
of the drug substance.
We would define ‘‘field study’’ as a
type of adequate and well-controlled
study designed to assess the
effectiveness and/or safety of a new
animal drug in the target animal under
conditions that closely approximate the
actual conditions of use.
The term ‘‘indication’’ would mean
‘‘the use for which the new animal drug
is approved or conditionally approved.’’
We would define ‘‘milk discard time’’
as the interval between the time of the
last administration of a new animal drug
and the time when the milk can be
safely consumed.
We would define ‘‘residue warning
statement’’ as a statement that warns
against the use of the new animal drug
in animals for which the withdrawal
period and/or milk discard time has not
been determined, and/or provides other
information to prevent illegal drug
residues in food products from animals
treated with the new animal drug.
The term ‘‘target animal’’ would mean
the species, or collection of species, of
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animals, and if applicable, the specific
subset(s) of animals (e.g., life stage,
production class, age, gender) for which
the new animal drug is approved or
conditionally approved. Particularly for
food-producing animals, new animal
drugs may be approved for use only
during a specific life stage (e.g.,
growing, pregnant, lactating),
production class (e.g., growing beef
steers and heifers fed in confinement for
slaughter, broiler chickens, finishing
pigs), age, or gender of the animal.
We would define ‘‘environmental
warning’’ as a warning that identifies
any potential hazard to the human
environment associated with the use of
the new animal drug. We would define
‘‘user safety warning’’ as a warning that
identifies any serious adverse reaction
or potential hazard to human health
associated with human exposure during
use of a new animal drug via contact,
inhalation, ingestion, injection, or by
other means.
The term ‘‘withdrawal period’’ would
mean the interval between the time of
the last administration of a new animal
drug and the time when the animal can
be safely slaughtered for food.
The proposed regulations would
provide definitions for terms associated
with key labeling components for new
animal drugs, including ‘‘immediate
container,’’ ‘‘package insert,’’
‘‘secondary container,’’ ‘‘small label,’’
‘‘shipping labeling,’’ ‘‘representative
Type B medicated feed labeling,’’ and
‘‘representative Type C medicated feed
labeling.’’
C. General Requirements (Proposed
§ 201.404)
The proposed rule would require the
labeling for approved or conditionally
approved new animal drugs to conform
to an application approved under
section 512 of the FD&C Act or
conditionally approved under section
571 of the FD&C Act (see proposed
§ 201.404(a)(1)).
The proposed rule would require the
labeling to be informative and accurate
and neither promotional in tone nor
false or misleading in any particular and
would require the labeling to be
updated if new information becomes
available to cause the labeling to
become inaccurate, false, or misleading,
in accordance with § 514.8 of this
chapter (see proposed § 201.404(a)(2)
and (3)).
The proposed rule would require
labeling conforming to this subpart to be
submitted to FDA per the earliest
applicable compliance date provided in
the schedule, unless § 201.404(b), (c), or
(d) was applicable (see proposed
§ 201.404(a)(4)). See also section VI for
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discussion of Proposed Effective/
Compliance Dates.
Labeling included in NADAs,
CNADAs, or supplements to NADAs or
CNADAs subject to § 514.8(c)(2) that are
submitted to FDA for approval more
than 180 days after the effective date of
any final rule based on this proposed
rule would be required to conform to
the regulations as part of the application
(see proposed § 201.404(a)(4)(i)).
The proposed rule would require
sponsors with NADAs, CNADAs, or
supplements to NADAs or CNADAs
subject to § 514.8(c)(2) that are pending
with FDA on the effective date of any
final rule based on this proposed rule,
or submitted within 180 days after the
effective date of any final rule based on
this proposed rule, to submit
conforming labeling as part of the
application or supplemental
application, or alternatively, as a
supplement to the approved application
or supplemental application within 180
days after the approval date of the
application or supplemental
application, as determined by FDA (see
proposed § 201.404(a)(4)(ii)).
The proposed rule would establish a
timeline for submission of supplements
with conforming labeling for marketed
new animal drugs originally approved
before the effective date of any final rule
based on this proposed rule, based on
NADA number (see proposed
§ 201.404(a)(4)(iii) through (vii)).
For an ANADA that references a new
animal drug for which the NADA has
been voluntarily withdrawn for reasons
other than safety or effectiveness, or that
references a new animal drug for which
the NADA has been withdrawn on the
basis of one or more grounds included
under section 512(e) of the FD&C Act
and the ANADA’s approval was not
affected by the withdrawal, the labeling
for such an ANADA would be required
to be submitted between the [effective
date of a final rule plus 1 year] and the
[effective date of a final rule plus 2
years] (see proposed § 201.404(a)(4)(iii)).
For an ANADA that references a new
animal drug for which the NADA has
not been withdrawn, consistent with
current practice, we expect that the
sponsor of such a generic new animal
drug will submit a supplemental
application to the ANADA to conform
the labeling of the generic new animal
drug with the revised labeling of the
RLNAD once the labeling of the RLNAD
has been revised in accordance with the
schedule in proposed § 201.404.
Sponsors of proprietary Type B or
Type C medicated feeds for which the
underlying data and labeling are
maintained in a VMF would be required
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to submit conforming labeling to the
VMF within 180 days after all
conforming labeling has been approved
for the NADA or CNADA that is the
approved or conditionally approved
source of the new animal drug used to
manufacture the proprietary medicated
feed (see proposed § 201.404(b)).
The labeling for new animal drugs
conditionally approved before the
effective date of a final rule would not
be required to comply with proposed
subpart H until an application for full
approval is submitted unless a
supplement subject to § 514.8(c)(2) is
submitted to the CNADA after the
effective date of a final rule (see
proposed § 201.404(c)). The conditional
approval is valid for 1 year and can be
renewed annually for up to a total of 5
years by the sponsor showing active
progress towards demonstrating
substantial evidence of effectiveness.
The conditional approval will be
terminated if substantial evidence of
effectiveness is not demonstrated
(section 571(d) of the FD&C Act).
The proposed rule would also
establish an alternative schedule for
submitting conforming labeling for
combination new animal drugs intended
for use in animal feed or drinking water
and approved, on or before the effective
date of a final rule, in accordance with
section 512(d)(4) of the FD&C Act, i.e.,
per the Animal Drug Availability Act
(ADAA) of 1996. Section 512(d)(4) was
amended as part of the Minor Use Minor
Species (MUMS) Act of 2004 to clarify
that only products approved under
section 512(b)(1) of the FD&C Act can be
used in ADAA combinations. Thus,
ADAA combination new animal drugs
exclude conditionally approved drugs
subject to section 571 of the FD&C Act.
These ADAA combination new animal
drugs generally provide for more than
one approved new animal drug (as a
Type A medicated article) to be mixed
into medicated feed or drinking water.
These ADAA combination new animal
drug approvals result in new
representative (‘‘Blue Bird’’) labeling for
medicated feeds containing the
combination (see proposed § 201.409).
Representative labeling for medicated
feed containing the approved
combination of new animal drugs
includes information from the approved
labeling for the individual drugs. Thus,
it would be appropriate that the labeling
for individual drugs included in the
combination be updated to conform to
any final regulations before
representative labeling for the feeds
containing the combination approval is
updated. However, the ADAA
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combination approval would occur after
the individual drugs are approved;
therefore, the NADA number for the
combination approval would be higher
than the NADA numbers for the
individual new animal drugs. Thus,
according to the schedule proposed in
§ 201.404(a)(4), the conforming labeling
for a combination approval would likely
need to be submitted before the
conforming labeling for the individual
drugs in the combination. To address
this problem, the proposed rule would
require the conforming labeling for the
combination new animal drug to be
submitted within 180 days of the
approval of all conforming labeling for
the individual new animal drugs used
in the combination (see proposed
§ 201.404(d)).
The range of NADA numbers
provided as ‘‘breakpoints’’ in the
proposed schedule for the submission of
conforming labeling are intended to
provide for a relatively uniform number
of labeling supplements during each 1year interval. The schedule would
require more recently approved new
animal drugs to conform to the
requirements first because they are more
likely to be consistent with the new
requirements than the labeling of older
new animal drugs. Sponsors of older
new animal drug applications would
have a longer amount of time to comply
with the new requirements. Table 1
provides these NADA ranges in the first
column. Table 1 provides in the second
column the number of currently
approved and marketed NADAs within
the ranges of NADAs calculated by FDA
as of September 2023 and adjusts for
ADAA combination new animal drugs
that would need to conform after all
individual new animal drugs in the
combination have conformed (see
proposed § 201.404(d)). The first row of
the second column of table 1 includes
ANADAs that reference a new animal
drug for which the NADA has been
voluntarily withdrawn for reasons other
than safety or effectiveness, or that
reference a new animal drug for which
the NADA has been withdrawn on the
basis of one or more of the grounds
included under section 512(e) of FD&C
Act and for which the ANADA’s
approval was not affected by the
withdrawal. Table 1 also provides in the
third column the number of currently
approved and marketed ANADAs with
a RLNAD that has not been withdrawn,
as calculated by FDA as of September
2023; these ANADAs are included in
the row that corresponds to the NADA
number for the RLNAD.
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TABLE 1—NUMBER OF AFFECTED APPLICATIONS AS OF SEPTEMBER 2023 1
NADA Nos.
ANADA with
a RLNAD 2
NADA
Total
certain ANADAs ...................................................................................................
N–141–299 ..........................................................................................................
N–140–999 ..........................................................................................................
N–114–999 ..........................................................................................................
N–044–999 ..........................................................................................................
3 104
101
105
116
86
9
86
87
68
66
113
187
192
184
152
Total ......................................................................................................................................
512
316
828
N–141–300
N–141–000
N–115–000
N–045–000
N–000–001
1 These
2 These
+;
to
to
to
to
numbers will be updated in a final rule.
are ANADAs with a RLNAD that has not been withdrawn, and they are in the row that corresponds to the NADA number for the
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RLNAD.
3 This number includes six ANADAs that reference a withdrawn NADA.
The proposed rule would provide
direction for situations in which it may
not be clear how a requirement in
subpart H applies to a particular new
animal drug, or whether it applies. FDA
approves and conditionally approves
new animal drugs for many species of
animals. For some new animal drugs,
certain sections or subsections of
labeling required by proposed subpart H
would not be applicable. For example,
new animal drugs approved or
conditionally approved for use in nonfood-producing animals (e.g., cats, dogs)
would not require the labeling
subsection entitled either ‘‘Withdrawal
Periods and Residue Warnings’’ or
‘‘Withdrawal Periods’’. As another
example, certain new animal drugs may
not have contraindications. We would
make the final determination in these
situations as to the applicability of
requirements in subpart H to specific
new animal drugs (see proposed
§ 201.404(e)).
In addition, some sections in subpart
H propose different options to meet the
labeling requirements. For example,
proposed § 201.405(b) would provide
various options for presenting the
‘‘Indications for Use’’ section on the
label for a prescription new animal
drug, depending on size of the label. In
those situations where the most
appropriate option is not clear, we
would make the final determination (see
proposed § 201.404(e)). Ordinarily, such
determinations would be made during
the review of the new animal drug and
its labeling.
When sponsors would submit labeling
for purposes of conforming to the
requirements of proposed subpart H
according to the schedule in proposed
§ 201.404(a)(4), the proposed rule would
require all labeling components for an
approved or conditionally approved
new animal drug to be provided in one
submission. FDA would refuse to file
labeling submissions intended to
conform to this subpart that are
incomplete. This would ensure that the
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content and format is consistent across
all the labeling components for a
particular new animal drug. Also, this
would enable FDA to review and
compare all labeling components at the
same time to ensure that they conform
to the proposed regulations when
finalized (see proposed § 201.404(f)).
The proposed rule would establish
general requirements for the format of
labeling of approved or conditionally
approved new animal drugs in proposed
§ 201.404(g). The format and content of
labeling for prescription new animal
drugs, OTC new animal drugs, or new
animal drugs for use in animal feeds
would be required to comply with the
general requirements in proposed
§ 201.404(g), as applicable, in addition
to format and content specific
requirements for each type of new
animal drug (see proposed §§ 201.405,
201.407, or 201.409, respectively).
The proposed rule would establish
requirements for the placement, size,
and prominence of the established name
relative to the proprietary name for
approved or conditionally approved
prescription new animal drugs in
proposed § 201.404(g)(1). These
requirements are in accordance with
§ 201.10(g)(1) and (2) (21 CFR
210.10(g)(1) and (2)) and section
502(e)(1)(B) of the FD&C Act.
The proposed rule would establish
requirements for the placement, size,
and prominence of the established name
relative to the proprietary name of
approved or conditionally approved
OTC new animal drugs and labeling for
approved or conditionally approved
new animal drugs for use in animal
feeds, excluding representative Type B
and Type C medicated feed labeling (see
proposed § 201.404(g)(2)).
The proposed rule would provide the
requirements for the placement, size,
and prominence of the established name
on representative Type B and Type C
medicated feed labeling for approved or
conditionally approved new animal
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drugs for use in animal feeds (see
proposed § 201.404(g)(3)).
The proposed rule would require
labeling text to be easy to read and with
letters that do not touch. For certain text
on labeling for new animal drugs, we
believe that black text on a white
background and use of a single type
style is the easiest to read. Accordingly,
the proposed rule would require that the
running text, section headings, and
subsection headings of package inserts
must be in black type and on a white
background and use a single type style
because package inserts provide full
prescribing information for prescription
new animal drugs and full product
information for OTC new animal drugs.
Black text on a white background also
would be required for representative
labeling for Type B and C medicated
feeds. For all other labeling components
for new animal drugs, other color
combinations would be allowed,
provided that there is sufficient contrast
between text and the background colors
to ensure readability. See proposed
§ 201.404(g)(4) and (5).
The proposed rule would establish
requirements for presentation of
graphics and designs on labeling for
approved or conditionally approved
new animal drugs (see proposed
§ 201.404(g)(6)). Representative labeling
for Type B and C medicated feeds
would not be permitted to have logos,
graphics, or designs other than
illustrations or tables that FDA
determines are necessary for proper use
of the medicated feed. This proposed
format is consistent with the purpose of
representative labeling for Type B and C
medicated feeds for use as template
labeling and is also consistent with the
format of representative labeling for
Type B and C medicated feeds currently
used in the medicated feeds industry.
The proposed rule would require the
presentation of graphics and designs on
other labeling components for approved
or conditionally approved new animal
drugs to comply with § 201.15(b)(1) (21
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CFR 201.15(b)(1)) and proposed
§ 201.404(a)(2) (see proposed
§ 201.404(g)(6)). If graphics are
incorporated into the background of
these labeling components, for any text
appearing over the graphics there would
need to be sufficient contrast between
the text and the graphics colors to
ensure readability of the text. The use of
compressed arrows on labeling would
be limited to the subsection entitled
either ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods,’’ in
accordance with the requirements in
proposed § 201.404(g)(8) (see proposed
§ 201.404(g)(6)).
The proposed rule would establish
minimum letter height or type size
requirements that would vary for each
labeling component and ensure
appropriate space on each component
while maintaining readability of text
(see proposed § 201.404(g)(7)).
Section headings and subsection
headings would be required to be in
bold type that prominently
distinguishes them from other approved
labeling information. Section headings
would be required to be left justified or
centered, whereas subsection headings
would be required to be left justified.
An exception would be the subsection
of labeling entitled either ‘‘Withdrawal
Periods and Residue Warnings’’ or
‘‘Withdrawal Periods,’’ in which the
subsection heading, and the contents of
the subsection, would be required to be
centered within compressed arrows (see
proposed § 201.404(g)(8)).
The proposed rule would require that,
if the National Drug Code is included on
labeling of new animal drugs, then it
must appear in accordance with 21 CFR
207.33 (see proposed § 201.404(h)).
The proposed rule would require all
words, statements, and other
information on the labeling for
approved or conditionally approved
new animal drugs to appear in English.
In addition, the proposed rule would
also establish requirements for
additional foreign language translations
of new animal drug labeling (see
proposed § 201.404(i)).
For approved or conditionally
approved prescription new animal
drugs, the proposed rule would require
that if any section or wording of a
labeling component is translated into a
foreign language, the entire full
prescribing information would also be
required to be translated into the foreign
language. In certain situations, FDA may
also require additional wording on other
labeling components for the
prescription new animal drug to be
translated into the foreign language.
These requirements would ensure that
all information necessary for the safe
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and effective use of the prescription
new animal drug would be provided in
the foreign language (see proposed
§ 201.404(i)(1)).
For approved or conditionally
approved OTC new animal drugs, the
proposed rule would require that if any
section or wording of a labeling
component is translated into a foreign
language, the entire full product
information would also be required to
be translated into the foreign language.
In certain situations, FDA may also
require additional wording on other
labeling components for the OTC new
animal drug to be translated into the
foreign language. These requirements
would ensure that all information
necessary for the safe and effective use
of the OTC new animal drug would be
provided in the foreign language (see
proposed § 201.404(i)(2)).
For approved or conditionally
approved new animal drugs for use in
animal feeds, the proposed rule would
require that if the labeling contains any
representation in a foreign language, all
labeling must also appear in the foreign
language (see proposed § 201.404(i)(3)).
For all situations where labeling for
new animal drugs is translated into a
foreign language, the translated wording
would be required to comply with the
format and content requirements for
prescription, OTC, or new animal drugs
for use in animal feeds in proposed
§ 201.405(a), § 201.407(a), or § 201.409,
respectively.
FDA may limit the number of
languages into which labeling
information is translated to ensure
clarity of information and the safe and
effective use of the new animal drug.
This proposed limitation would avoid
multipage labeling in multiple
languages. We intend for this limitation
to reduce medication errors and reduce
the time needed to locate information
on labeling (see proposed
§ 201.404(i)(4)).
The proposed rule would allow the
predominant language to be substituted
for English on the labeling for new
animal drugs distributed solely in the
Commonwealth of Puerto Rico or in a
Territory where the predominant
language is other than English. We may
determine that such new animal drugs
may be altogether exempt from the
requirements in proposed § 201.404(i)
(see proposed § 201.404(j)).
D. Content and Format for Prescription
(Rx) New Animal Drug Labeling—
Overview (Proposed § 201.405)
The proposed rule provides content
and format requirements for all
components of labeling for approved or
conditionally approved prescription
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18271
(Rx) new animal drugs. Proposed
§ 201.405 would not apply to approved
or conditionally approved new animal
drugs intended for use in or on animal
feed under the professional supervision
of a licensed veterinarian because, in
accordance with section 504(a) of the
FD&C Act, such drugs are approved or
conditionally approved as VFD drugs.
Proposed § 201.409 would establish the
content and format requirements for all
components of labeling for approved or
conditionally approved new animal
drugs intended for use in animal feeds
that are subject to part 558, including
VFD drugs.
The proposed rule would require that
labeling sections or subsections that do
not apply be omitted from the labeling
for approved or conditionally approved
Rx new animal drugs (see proposed
§ 201.405). For example, Rx new animal
drugs approved or conditionally
approved for use in non-food-producing
animals (e.g., cats, dogs) would not
require the labeling subsection entitled
either ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods’’.
FDA determines the final content of
each applicable section of labeling
during the review of each new animal
drug as part of the approval process.
Full prescribing information for Rx
new animal drugs would include all
information necessary for safe and
effective use of the Rx new animal drug.
Thus, all approved or conditionally
approved Rx new animal drugs would
be required to provide a labeling
component that includes full
prescribing information. The proposed
rule would identify the information that
would be required to be included on the
labeling component that would provide
full prescribing information for Rx new
animal drugs. If a package insert is
provided with an Rx new animal drug,
the proposed rule would require the
package insert to include full
prescribing information. If only partial
information is provided on a package
insert, the user may mistakenly assume
the package insert includes complete
information on the safe and effective use
of the drug when in fact it does not. If
no package insert is provided with an
Rx new animal drug, the secondary
container labeling would be required to
include full prescribing information (see
proposed § 201.405(a)).
The label is the labeling component
that appears on the immediate
container, which is the container in
contact with the drug. The proposed
rule would establish content and format
requirements for the label for an
approved or conditionally approved Rx
new animal drug (see proposed
§ 201.405(b)) and for a small label for an
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approved or conditionally approved Rx
new animal drug that FDA determines
lacks sufficient space to comply with
proposed § 201.405(b) (see proposed
§ 201.405(c)).
For purposes of proposed subpart H,
the proposed rule would define a
package insert for an approved or
conditionally approved Rx new animal
drug as a labeling component that
contains full prescribing information
and is included with the immediate
container or secondary container or is
attached to the label (see proposed
§ 201.403). Where the package insert is
attached to the label, which is
sometimes referred to as, for example,
‘‘extended labeling,’’ ‘‘onserts,’’ or
‘‘outserts,’’ for purposes of proposed
subpart H, the package insert providing
full prescribing information and
attached to the label would need to
comply with proposed § 201.405(a). The
label would need to comply with
proposed § 201.405(b) or (c), as
applicable.
FDA considers the secondary
container for a new animal drug to be
the packaging that surrounds the
immediate container. The proposed rule
would establish content and format
requirements for secondary container
labeling for an approved or
conditionally approved Rx new animal
drug (see proposed § 201.405(d)). If a
package insert is provided with an Rx
new animal drug, then the secondary
container labeling would be required to
comply with proposed § 201.405(d), and
the package insert would be required to
provide full prescribing information to
comply with proposed § 201.405(a). If
no package insert is provided with an
Rx new animal drug, the proposed rule
would require full prescribing
information to appear on the secondary
container labeling (see proposed
§ 201.405(a)).
In accordance with the definition of
‘‘label’’ in section 201(k) of the FD&C
Act, information on the label must also
appear on an outside container or
wrapper of the retail package, if it exists,
or be easily legible through the outside
container or wrapper. For purposes of
these proposed regulations, FDA
considers the secondary container to be
an ‘‘outside container or wrapper of the
retail package’’ for new animal drugs.
Therefore, if a secondary container
exists, the proposed rule would require
the secondary container labeling to
include all information that would be
on the label in accordance with
proposed § 201.405(b) or (c), unless the
information on the label is easily legible
through the secondary container (see
proposed § 201.405(a) and (d)).
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Shipping labeling is associated with
the outermost carton containing a new
animal drug, which is intended for
shipping, but not displaying the
product. The proposed rule would
establish content and format
requirements for the shipping labeling
of approved or conditionally approved
Rx new animal drugs, including a
requirement that such shipping labeling
identify the new animal drug, the
manufacturer, and drug storage and
handling information. However,
approved or conditionally approved Rx
new animal drugs that are controlled
substances would not include
information that identifies the drug, in
accordance with § 1301.74(e) (21 CFR
1301.74(e)), to guard against storage or
in-transit losses (see proposed
§ 201.405(e)).
Depending on how a sponsor intends
to sell or display an approved or
conditionally approved Rx new animal
drug, there may be other containers
such as display cartons and multiple
unit (multi-unit) cartons that contain
immediate containers or secondary
containers. These containers may be
packaged in shipping cartons. The
proposed rule would establish content
and format requirements for the labeling
of these other containers for Rx new
animal drugs (see proposed
§ 201.405(f)).
Labeling sections and subsections for
Rx new animal drugs would not be
numbered. Headings of sections and
subsections that would be required to
appear verbatim on labeling are
identified in the proposed regulations in
quotations. Similarly, certain other
labeling text would be required to
appear verbatim on labeling; this text is
also identified in the proposed
regulations in quotations.
The proposed rule would require the
labeling of approved or conditionally
approved Rx new animal drugs to
comply with other applicable
requirements in proposed subpart H (see
proposed § 201.405).
1. Labeling Providing Full Prescribing
Information (Proposed § 201.405(a))
FDA uses the term ‘‘full prescribing
information’’ to identify all information
necessary for the safe and effective use
of approved or conditionally approved
Rx new animal drugs. The proposed
rule would establish content and format
requirements for the component of
labeling that provides full prescribing
information for approved or
conditionally approved Rx new animal
drugs (see proposed § 201.405(a)).
If a package insert is provided with an
approved or conditionally approved Rx
new animal drug, the proposed rule
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would require the package insert to
include full prescribing information (see
proposed § 201.405(a)). If a package
insert is provided with an approved or
conditionally approved Rx new animal
drug, any secondary container labeling
would be required to comply with
proposed § 201.405(d).
If a package insert is not provided
with an approved or conditionally
approved Rx new animal drug, then
secondary container labeling would be
required, and the secondary container
labeling would be required to provide
full prescribing information (see
proposed § 201.405(a)). If full
prescribing information is provided on
the secondary container labeling, in
accordance with section 201(k) of the
FD&C Act, proposed § 201.405(a) would
allow the secondary container labeling
to exclude any portions of full
prescribing information that would be
required to appear on the label if such
information is easily legible through the
secondary container (see proposed in
§ 201.405(d)).
The proposed rule would require the
following information to be presented in
full prescribing information for
approved or conditionally approved Rx
animal drugs and in the following order:
a. Drug product identification. The
proposed rule would require this
section of full prescribing information to
include the proprietary name of the
finished drug product and the
established name of the drug product. If
not included as part of the established
name of the drug product, the route(s)
of administration and dosage form of the
finished drug product would be
required to be included in this section
as well (see proposed § 201.405(a)(1)(i)
through (iv)).
The established name and strength or
concentration of each active ingredient
would also be required. The strength or
concentration of each active ingredient
would be allowed to be excluded from
full prescribing information provided on
a package insert if the package insert
applies to multiple strengths or
concentrations for the same Rx new
animal drug (see proposed
§ 201.405(a)(1)(v)).
If FDA determines that identifying the
pharmacological class of an Rx new
animal drug on labeling would be
helpful in facilitating its safe and
effective use by the prescribing
veterinarian, the proposed rule would
require that the pharmacological class
be included in this section of full
prescribing information (see proposed
§ 201.405(a)(1)(vi)).
For Rx new animal drugs that are
controlled substances, symbols
provided in part 1302 (21 CFR part
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1302) to identify the controlled
substance schedule would also appear
in this section of full prescribing
information. See proposed
§ 201.405(a)(1)(vii).
Prescription statement. The proposed
rule would require this section of full
prescribing information to include the
prescription statement, ‘‘Caution:
Federal law restricts this drug to use by
or on the order of a licensed
veterinarian.’’ Prescription new animal
drugs are limited to use under the
professional supervision of a licensed
veterinarian (section 503(f)(1)(A) of the
FD&C Act). The prescription statement
would indicate that the Rx new animal
drug is restricted to use by or under the
order of a licensed veterinarian.
Including the prescription statement on
full prescribing information would be
consistent with its inclusion on the
label for Rx new animal drugs, which is
required by section 503(f)(4) of the
FD&C Act. The requirement for
including the prescription statement as
part of full prescribing information is
proposed under the authority granted to
FDA under sections 502(a), 201(n), and
701(a) of the FD&C Act. See proposed
§ 201.405(a)(2).
c. Conditional approval statement.
For conditionally approved Rx new
animal drugs, the proposed rule would
require this section of full prescribing
information to include, in accordance
with section 571(f)(1)(A) of the FD&C
Act, the statement indicating
conditional approval by FDA and the
application number: ‘‘conditionally
approved by FDA pending a full
demonstration of effectiveness under
application number [insert number]’’.
This statement would be required to be
prominent and conspicuous (see
proposed § 201.405(a)(3)).
d. Boxed warnings. For Rx new
animal drugs requiring boxed warnings,
the proposed rule would require this
section of full prescribing information to
include the boxed warnings. Boxed
warnings convey the most significant
risks associated with the use of a Rx
new animal drug. If applicable to the
product, they would appear at this
prominent location. An upper case
‘‘WARNING’’ heading would be
included in the box, and the box,
heading, and contents would be bolded.
The boxed warning would be brief, with
reference to more detailed information
in other sections of full prescribing
information if applicable (see proposed
§ 201.405(a)(4)).
e. Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use, in
accordance with § 530.41 (21 CFR
530.41), the proposed rule would
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require this section of full prescribing
information to include an extralabel use
prohibition statement that begins with
the phrase: ‘‘Federal law prohibits the
extralabel use of this drug . . .’’ and
concludes with a description of the
prohibition as described in § 530.41 (see
proposed § 201.405(a)(5)). For example,
‘‘Federal law prohibits the extralabel
use of this drug in lactating dairy cows.’’
Certain new animal drugs are
prohibited from extralabel use in some
or all animals, in accordance with
§ 530.41. This information is critical for
inclusion on labeling. If a user fails to
comply with an extralabel use
prohibition statement, there could be
serious safety consequences for the
target animal, or in the case of a foodproducing animal, also for humans
consuming food derived from the target
animal.
f. ‘‘Description.’’ The proposed rule
would require this section of full
prescribing information to have the
heading ‘‘Description,’’ followed by a
description of the new animal drug. The
description would include the
proprietary name of the finished drug
product and established name of the
drug product, and the route(s) of
administration and dosage form if not
included as part of the established
name. The description would also
include identifying characteristics of the
dosage form, such as color, shape,
coating, scoring, and imprinting. All
approved and available strengths or
concentrations of the new animal drug
to which full prescribing information
applies would need to be identified in
this section of full prescribing
information. If the drug product was
sterile, this fact would also be identified
in this section of full prescribing
information (see proposed
§ 201.405(a)(6)).
The established name of each inactive
ingredient would be required to be
included in the ‘‘Description’’ section of
full prescribing information. The
proposed rule would require all inactive
ingredients to be listed in decreasing
order of predominance, by weight or
concentration (see proposed
§ 201.405(a)(6)(viii)). FDA believes that
listing inactive ingredients in decreasing
order of predominance based on either
weight or concentration would provide
the most clinically useful information to
users.
In accordance with section
502(e)(1)(A)(iii) of the FD&C Act, the
proposed rule would not require the
listing of inactive ingredients on full
prescribing information under
circumstances that would result in
disclosure of trade secret information.
Therefore, where sponsors believe the
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listing of inactive ingredients on
product labeling would result in
disclosure of trade secret information,
they would be able to request exemption
from this labeling requirement under
proposed § 201.411. If an exemption
from the listing of inactive ingredients
to avoid divulgence of trade secret
information is granted under § 201.411,
this section of full prescribing
information would be required to state:
‘‘Certain inactive ingredients are not
listed to avoid disclosing trade secret
information.’’ (see proposed
§ 201.405(a)(6)(viii)(A)).
Section 502(e)(1)(B) of the FD&C Act
allows an exemption from listing
inactive ingredients on the label of Rx
drugs if doing so would be
impracticable. The current regulations
at § 201.105(b)(5) for Rx animal drugs
state that names of flavorings, perfumes,
certain color additives, and ‘‘trace
amounts of harmless substances added
solely for individual product
identification’’ may be exempt from
listing on the labels for products other
than for oral use. The regulations at
§ 201.105 predate the requirements in
section 502(e)(1)(B) of the FD&C Act and
are outdated. The proposed rule would
replace the requirements for labels for
approved or conditionally approved Rx
new animal drugs currently provided in
§ 201.105(b) with the requirements in
proposed § 201.405(b) and (c) (see
discussion in section V.D.2. and 3).
Thus, the labels for approved or
conditionally approved Rx new animal
drugs would no longer qualify for the
exemptions currently identified in
§ 201.105(b)(5).
If under proposed § 201.411 FDA
grants an exemption from listing
inactive ingredients because their listing
would be impracticable, this section of
full prescribing information would need
to state the following: ‘‘Certain inactive
ingredients are not listed because their
listing would be impracticable.’’ (see
proposed § 201.405(a)(6)(viii)(B)).
g. ‘‘Indications for Use.’’ This section
of full prescribing information would be
required to have the heading
‘‘Indications for Use,’’ followed by the
approved or conditionally approved
indication(s) and target animal(s) in the
following format: ‘‘For [indication(s)] in
[target animal(s)]’’ (see proposed
§ 201.405(a)(7)(i)).
Consistent with regulations for the
labeling of Rx human products in
§ 201.57(c)(2)(i)(A), if a Rx new animal
drug is approved or conditionally
approved for use only under specific
conditions, e.g., in conjunction with a
primary mode of therapy, special diet,
surgery, behavioral modification, or
some other drug, the proposed rule
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would require that this information be
specified in the ‘‘Indications for Use’’
section of full prescribing information
(see proposed § 201.405(a)(7)(ii)).
If, in approving or conditionally
approving an application, FDA requires,
for safety and/or effectiveness reasons, a
statement(s) on labeling identifying
animals for which the Rx new animal
drug has not been approved or
conditionally approved, the proposed
rule would require that statement(s) to
appear in the ‘‘Indications for Use’’
section of full prescribing information
(see proposed § 201.405(a)(7)(iii)). We
currently require the statement(s)
proposed in § 201.405(a)(7)(iii) to
appear on labeling of some approved
new animal drugs, particularly new
animal drugs for use in food-producing
animals, to clarify the target animal for
which the drug is approved. The
statements are typically required if we
determine that unapproved use of a
drug in animals similar to the target
animal(s) is reasonably foreseeable and
we believe that inclusion of such a
statement on the labeling of the new
animal drug could increase the safe and
effective use of the drug. For example,
feedlot beef cattle are not intended to
provide milk for human consumption.
Therefore, we will not likely require an
evaluation of the human food safety of
a new animal drug in lactating dairy
cows if the new animal drug is only to
be approved for use in feedlot cattle.
However, we will often require a
statement on labeling that the drug is
not for use in lactating dairy cows
intended to produce milk for human
consumption to avoid use of the drug in
this unapproved and unevaluated
manner.
The statement(s) proposed in
§ 201.405(a)(7)(iii) is not intended to
prohibit extralabel use of approved new
animal drugs allowed under specific
circumstances, in accordance with
section 512(a)(4) of the FD&C Act and
part 530 (21 CFR part 530), but would
help to clarify that some specific uses
are extralabel and have not been
evaluated for safety and effectiveness by
FDA. Currently, there is no uniform
place on the labeling for new animal
drugs for such statements to appear. If
we require such statements on labeling
to ensure safe and effective use of a new
animal drug, the proposed rule would
require the statements to be placed
within the ‘‘Indications for Use’’ section
of full prescribing information.
Inclusion of such statements in the
‘‘Indications for Use’’ section would not
necessarily preclude also including
similar statements in other sections or
subsections of full prescribing
information if warranted. For example,
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it may be appropriate to include a
similar statement as a residue warning
statement in the ‘‘Withdrawal Periods
and Residue Warnings’’ subsection to
expand upon human food safety risks of
the extralabel use of the new animal
drug in animals other than the target
animal.
h. ‘‘Dosage and Administration.’’ The
proposed rule would require this
section of full prescribing information to
have the heading ‘‘Dosage and
Administration,’’ followed by the
dosage and administration information
for the new animal drug for each
indication and target animal (see
proposed § 201.405(a)(8)).
Sometimes FDA requires additional
labeling for Rx new animal drugs that
provides important information for the
animal owner or person treating the
animal. If such additional labeling is
required, the proposed ‘‘Dosage and
Administration’’ section of full
prescribing information would advise
the veterinarian to provide the
additional labeling to the animal owner
or person treating the animal (see
proposed § 201.405(a)(8)(i)).
The remainder of this section of full
prescribing information would be
required to include information
necessary for treatment of the animal
with the Rx new animal drug in
accordance with FDA approval or
conditional approval, including: route(s)
of administration and specific site(s) of
administration, if applicable; dose or
dose range; intervals between doses, if
applicable; and duration of treatment.
For some injectable products, FDA may
require a statement of the maximum
volume per injection site to facilitate the
drug’s safe and effective use, and the
proposed rule would require this
information to be included in this
section of full prescribing information.
Also, certain animal populations may
require modifications to the dosage and
administration for safe and effective use.
These modifications would be required
to appear in this section of full
prescribing information. Other required
dosage and administration information
would also be included in this section
of full prescribing information. See
proposed § 201.405(a)(8).
i. ‘‘Contraindications.’’ For Rx new
animal drugs with contraindications,
the proposed rule would require this
section of full prescribing information to
have the heading ‘‘Contraindications,’’
followed by the contraindications (see
proposed § 201.405(a)(9)). As defined in
proposed § 201.403, a contraindication
would include any situation in which
the new animal drug should not be used
because the risk of use clearly
outweighs any possible benefit to the
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animal and includes only known
hazards.
j. ‘‘Warnings and Precautions.’’ The
proposed rule would require this
section of full prescribing information
for all approved or conditionally
approved Rx new animal drugs, and it
would have the heading ‘‘Warnings and
Precautions’’ (see proposed
§ 201.405(a)(10)). As defined in
proposed § 201.403, warnings would
describe any serious adverse reactions
or potential hazards associated with the
use of the new animal drug. In addition,
precautions would be defined as any
special care to be exercised for safe and
effective use of the new animal drug,
which may include recommended
screening, monitoring, or diagnostic
tests. Multiple subsections, if
applicable, would be included in the
‘‘Warnings and Precautions’’ section of
full prescribing information as
described below and in the following
order, and the warnings and precautions
would be provided in the applicable
subsection:
i. ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods.’’ All
Rx new animal drugs approved or
conditionally approved for use in foodproducing animals would be required to
have as the first subsection of the
‘‘Warnings and Precautions’’ section of
full prescribing information a
subsection entitled either ‘‘Withdrawal
Periods and Residue Warnings’’ or
‘‘Withdrawal Periods’’ (see proposed
§ 201.405(a)(10)(i)). This subsection
would provide all human food safety
warnings, including milk discard times,
withdrawal periods, and residue
warning statements, as applicable to the
new animal drug.
As defined in proposed § 201.403, a
withdrawal period is the interval
between the time of the last
administration of a new animal drug
and the time when the animal can be
safely slaughtered for food. Withdrawal
periods apply to all food-producing
animals. As defined in proposed
§ 201.403, a milk discard time is the
interval between the time of the last
administration of a new animal drug
and the time when the milk can be
safely consumed. Milk discard times
apply to female animals that produce
milk for human consumption. A new
animal drug approved for use in female
animals that produce milk for human
consumption may have both a milk
discard time and a withdrawal period.
As defined in proposed § 201.403, a
residue warning statement warns
against the use of the new animal drug
in animals for which the withdrawal
period and/or milk discard time has not
been determined, and/or provides other
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information to prevent illegal drug
residues in food products from animals
treated with the new animal drug.
If there are any residue warning
statements for the new animal drug, the
proposed rule would require this
subsection of full prescribing
information to have the title
‘‘Withdrawal Periods and Residue
Warnings.’’ If there are no residue
warning statements associated with the
new animal drug, this subsection of full
prescribing information would be
required to have the title ‘‘Withdrawal
Periods’’ (see proposed
§ 201.405(a)(10)(i)(A)).
If the new animal drug is approved or
conditionally approved for use in foodproducing animals excluding female
animals that produce milk for human
consumption, the proposed rule would
require this subsection of full
prescribing information to include the
withdrawal period(s) followed by any
residue warning statements (see
proposed § 201.405(a)(10)(i)(B)).
If the new animal drug is approved or
conditionally approved for use in foodproducing animals excluding female
animals that produce milk for human
consumption and there is no
withdrawal period, the proposed rule
would require this subsection of full
prescribing information to state, ‘‘No
withdrawal period is required when
used according to labeling.’’ This
statement would be followed by any
residue warnings statements (see
proposed § 201.405(a)(10)(i)(C)).
If the new animal drug is approved or
conditionally approved for use in
female animals that produce milk for
human consumption, the proposed rule
would require this subsection of full
prescribing information to include the
milk discard time(s), followed by the
withdrawal period(s), followed by any
residue warning statements (see
proposed § 201.405(a)(10)(i)(D)).
If the new animal drug is approved or
conditionally approved for use in
female animals that produce milk for
human consumption, and there is a milk
discard time(s) but no withdrawal
period, the proposed rule would require
this subsection of full prescribing
information to include the milk discard
time(s), followed by the statement, ‘‘No
withdrawal period is required when
used according to labeling.’’ This
statement would be followed by any
residue statements (see proposed
§ 201.405(a)(10)(i)(E)).
If the new animal drug is approved or
conditionally approved for use in
female animals that produce milk for
human consumption and there is no
milk discard time but there is a
withdrawal period(s), the proposed rule
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would require this subsection of full
prescribing information to include the
withdrawal period(s), followed by the
statement, ‘‘No milk discard time is
required when used according to
labeling.’’ This statement would be
followed by any residue warnings
statements (see proposed
§ 201.405(a)(10)(i)(F)).
If the new animal drug is approved or
conditionally approved for use in
female animals that produce milk for
human consumption and there is no
milk discard time and no withdrawal
period, the proposed rule would require
this subsection of full prescribing
information to state, ‘‘No milk discard
time and no withdrawal period is
required when used according to
labeling.’’ This statement would be
followed by any residue warnings
statements (see proposed
§ 201.405(a)(10)(i)(G)).
Currently, new animal drugs
approved for use in food-producing
animals that have no milk discard time
and/or withdrawal period may or may
not indicate this information on
labeling. If this information is not
provided on labeling, potentially it
could be confusing to the user of the
new animal drug as to whether or not
there is a milk discard time or
withdrawal period for the new animal
drug. Requiring this subsection of full
prescribing information for all new
animal drugs approved or conditionally
approved for use in food-producing
animals, and requiring a statement, if
appropriate, to indicate that there is no
milk discard time or withdrawal period
when the new animal drug is used
according to labeling, will better ensure
the safe use of animal drugs in foodproducing animals.
To further highlight for users this
critical subsection of full prescribing
information, the title of this subsection
and all information in this subsection
would be required to be centered and
placed entirely within compressed
arrows, in accordance with proposed
§ 201.404(g)(8). The compressed arrows
would be black for package inserts, or a
color that clearly contrasts from
background colors for other approved
labeling (see proposed
§ 201.405(a)(10)(i)(A)). Currently, the
compressed arrows are used voluntarily,
although not consistently, on the
labeling for many new animal drugs
approved for use in food-producing
animals. Currently other statements not
associated with human food safety may
also appear within the compressed
arrows. The proposed rule would limit
the use of compressed arrows to the
subsection entitled either ‘‘Withdrawal
Periods and Residue Warnings’’ or
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‘‘Withdrawal Periods’’ (see proposed
§ 201.404(g)(6)), which would only
contain human food safety information.
ii ‘‘User Safety Warnings.’’ The
proposed rule would require this
subsection of the ‘‘Warnings and
Precautions’’ section of full prescribing
information to have the heading ‘‘User
Safety Warnings,’’ followed by the user
safety warnings. As defined in proposed
§ 201.403, a user safety warning would
be a warning that identifies serious
adverse reactions or potential hazards to
human health associated with human
exposure during use of a new animal
drug via contact, inhalation, ingestion,
injection, or by other means. This
information would be required to
prevent or decrease the risk of harm to
humans.
The first statements that would be
included in this subsection of full
prescribing information are: ‘‘Not for
use in humans. Keep out of reach of
children.’’ The subsection would next
list all additional user safety warnings
listed in decreasing order of severity or
frequency. The final information that
would be included in this subsection of
full prescribing information would be a
sentence explaining how to obtain
Safety Data Sheet(s) for the drug.
Chemical manufacturers, distributors,
and/or importers are required pursuant
to 29 CFR 1910.1200(g) to provide
Safety Data Sheets for each hazardous
chemical to downstream users to
communicate information on these
hazards. Safety Data Sheets include
information such as the properties of
each chemical; their physical, health,
and environmental health hazards;
protective measures; and safety
precautions for handling, storing, and
transporting the chemical. The sentence
in this subsection of full prescribing
information would be required to be
formatted as follows: ‘‘To obtain a
Safety Data Sheet(s), contact [insert
name of manufacturer] at [insert
manufacturer’s telephone number] or
[insert manufacturer’s website].’’ See
proposed § 201.405(a)(10)(ii).
iii. ‘‘Animal Safety Warnings and
Precautions.’’ For Rx new animal drugs
with target animal safety warnings and
precautions, the proposed rule would
require this subsection of the ‘‘Warnings
and Precautions’’ section of full
prescribing information to have the
heading ‘‘Animal Safety Warnings and
Precautions,’’ followed by the target
animal safety warnings and precautions
(see proposed § 201.405(a)(10)(iii)).
Target animal safety warnings identify
any serious adverse reactions or
potential hazards to the target animal(s)
associated with the use of the new
animal drug. Precautions for Rx new
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animal drugs often include
recommendations for specific screening,
monitoring, diagnostic tests, or special
care that should be taken by the
prescribing veterinarian for safe and
effective use of the new animal drug
(see definition in proposed § 201.403).
The heading of the subsection would
include the term ‘‘animal safety
warnings’’, i.e., ‘‘Animal Safety
Warnings and Precautions,’’ because we
believe the term ‘‘animal safety
warnings’’ is more familiar to users of
Rx new animal drugs than ‘‘target
animal safety warnings.’’
Precautions are sometimes difficult to
distinguish from target animal safety
warnings. Currently, target animal safety
warnings and precautions are
sometimes presented separately on the
labeling for Rx new animal drugs.
However, because the two sets of
information are often closely related, it
is advantageous to combine them into
one subsection of full prescribing
information.
Warnings and precautions are
combined in the ‘‘Highlights’’ and ‘‘Full
Prescribing Information’’ for human Rx
drugs and biologics (see §§ 201.56 and
57). Similarly, combining target animal
safety warnings and precautions in the
‘‘Animal Safety Warnings and
Precautions’’ subsection of full
prescribing information would be less
burdensome for sponsors of Rx new
animal drugs because sponsors would
not be required to distinguish one from
the other.
iv. ‘‘Environmental Warnings.’’ For
approved or conditionally approved
new animal drugs that have
environmental warnings, the proposed
rule would require this subsection of the
‘‘Warnings and Precautions’’ section of
full prescribing information to have the
heading ‘‘Environmental Warnings,’’
followed by the environmental warnings
(see proposed § 201.405(a)(10)(iv)).
FDA’s regulations at 21 CFR part 25
implementing the National
Environmental Policy Act (NEPA), 42
U.S.C. 4321 et seq., address the
environmental impact considerations
required for products regulated by FDA,
including new animal drugs. Under
NEPA, the responsible Agency official
examines the environmental risks of the
proposed action and the alternative
courses of action, selects a course of
action, and ensures that any necessary
mitigating measures are implemented as
a condition for approving the selected
course of action (see 21 CFR 25.40(e)).
In some instances, sponsors may choose
to include environmental warnings on
the labeling for their new animal drugs
as a means to mitigate or reduce the
potential for environmental impacts to
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occur from the use or disposal of the
drug (see 21 CFR 25.45). These warnings
would generally include information to
prevent or decrease the risk of any
environmental effects. The proposed
rule would require any environmental
warnings applicable to the new animal
drug that are included in an approved
or conditionally approved application
be provided in this subsection of full
prescribing information (see proposed
§ 201.405(a)(10)(iv)).
v. ‘‘Other Warnings.’’ For new animal
drugs having warnings not more
appropriately placed in other ‘‘Warnings
and Precautions’’ subsections, the
proposed rule would require the last
subsection of the ‘‘Warnings and
Precautions’’ section of full prescribing
information to have the heading ‘‘Other
Warnings,’’ followed by those warnings
(see proposed § 201.405(a)(10)(v)).
k. ‘‘Adverse Reactions.’’ For Rx new
animal drugs that we determine have
adverse reactions, this section of full
prescribing information would be
required to have the heading ‘‘Adverse
Reactions,’’ followed by the adverse
reactions (see proposed
§ 201.405(a)(11)). Adverse reactions
would be defined in proposed § 201.403
as undesirable effects, reasonably
associated with the use of the drug
product, that may occur as part of the
pharmacological action of the drug or
that may be unpredictable in
occurrence. The proposed rule would
require this section of full prescribing
information to include adverse reactions
that occur with use of the Rx new
animal drug and with use of drugs in
the same pharmacologically active and
chemically related classes, if applicable.
Furthermore, we may require additional
information as necessary for the
prescribing veterinarian to interpret the
adverse reactions, such as the total
number of animals exposed to the drug
and the extent and nature of exposure.
The proposed rule would also require
that adverse reactions be presented
within the following categories, as
applicable, in decreasing order of
severity or frequency: preapproval
experience, foreign market experience
known prior to U.S. approval for drugs
also commercially marketed outside of
the United States, and post-approval
experience (see proposed
§ 201.405(a)(11)). For previously
approved Rx new animal drugs for
which the labeling would be updated in
accordance with the schedule provided
in this rule, if the preapproval
experience and/or foreign market
experience categories were not included
on full prescribing information when
the drug was approved, we may allow
one or both of these subsections to be
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excluded from the ‘‘Adverse Reactions’’
section of full prescribing information if
we determine that including such
information is not necessary to ensure
the safe and effective use of the drug.
Post-approval experience would
typically be added to labeling of the
drug after it has been approved in the
United States and if additional adverse
drug experiences (as defined by § 514.3)
associated with the use of the drug have
been identified.
l. ‘‘Contact Information.’’ The
proposed rule would require this
section of full prescribing information to
have the heading ‘‘Contact
Information,’’ followed by the sponsor’s
contact information for veterinarians or
consumers to facilitate requesting
additional information or to report
suspected adverse drug experiences.
FDA’s contact information for voluntary
reporting of adverse drug experiences
for animal drugs would also be required.
Requiring contact information on new
animal drug labeling increases the
likelihood that a user will report
adverse drug events to the sponsor and/
or to the Center for Veterinary Medicine
(CVM). Increasing the likelihood of
receiving adverse drug event reports
would allow new animal drug sponsors
and CVM to better monitor and detect
emerging safety issues with approved or
conditionally approved new animal
drugs on the market. Any increase in
adverse drug event reporting and
monitoring resulting from this proposed
requirement would benefit both animal
and human health.
The sponsor’s contact information
would be the name of the manufacturer,
packer, or distributor, whichever is
identified in the ‘‘Name and place of
business’’ section of full prescribing
information per proposed
§ 201.405(a)(22). If more than one
business is identified in the ‘‘Name and
place of business’’ section of full
prescribing information, the drug
sponsor would select the most
appropriate of these businesses to use in
the ‘‘Contact Information’’ section to
provide additional information about
the Rx new animal drug and to contact
regarding suspected adverse drug
experiences.
The statements in this section of full
prescribing information would be
required to be structured as follows:
‘‘Contact [insert name of business] at
[insert business telephone number] or
[insert business web address]. To report
suspected adverse drug experiences,
contact [insert name of business] at
[insert business telephone number]. For
additional information about reporting
adverse drug experiences for animal
drugs, contact FDA at [insert current
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FDA telephone number for voluntary
reporting of adverse drug experiences]
or [insert current FDA web address for
voluntary reporting of adverse drug
experiences].’’ See proposed
§ 201.405(a)(12). Sponsors can search
FDA’s website or contact FDA by
telephone to find the current FDA
telephone number and web address for
voluntary reporting of adverse drug
experiences for animal drugs.
m. ‘‘Information for Animal Owner.’’
For Rx new animal drugs required to
have additional information to be
communicated by the prescribing
veterinarian to the animal owner or
person treating the animal to ensure safe
and effective use of the Rx new animal
drug, the proposed rule would require
this section of full prescribing
information to have the heading
‘‘Information for Animal Owner,’’
followed by the specific information.
For some new animal drugs, FDA may
determine it is necessary for sponsors to
provide the animal owner or person
treating the animal with additional
labeling, such as a ‘‘client information
sheet,’’ to ensure the safe and effective
use of the Rx new animal drug. If we
determine that such additional labeling
is necessary, a printed copy of the
additional labeling would be required to
be attached to or accompany the
package insert or secondary container
labeling if no package insert is provided.
See proposed § 201.405(a)(13).
n. ‘‘Clinical Pharmacology.’’ For Rx
new animal drugs required to include
clinical pharmacology information on
labeling, the proposed rule would
require this section of full prescribing
information to have the heading
‘‘Clinical Pharmacology,’’ followed by
the clinical pharmacology information
for the Rx new animal drug in the target
animal(s). The required information
would be relevant for understanding the
relationship between dose, systemic
drug exposure, safety, and clinical
effectiveness. This information may
help the prescribing veterinarian to
predict how the Rx new animal drug
would perform in the different animal
patient populations likely to be
encountered under clinical use
conditions. This section of full
prescribing information would be
required to include the following three
separate subsections, as applicable to
the Rx new animal drug: ‘‘Mechanism of
action,’’ ‘‘Pharmacodynamics,’’ and
‘‘Pharmacokinetics’’ (see proposed
§ 201.405(a)(14)).
o. ‘‘Microbiology.’’ For antimicrobial
Rx new animal drugs, the proposed rule
would require this section of full
prescribing information to have the
heading ‘‘Microbiology,’’ followed by a
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description of microbiologic data
associated with the studies used to
support the effectiveness of the drug
against the indicated pathogens. The
microbiology data would be required to
be restricted to organisms named in the
approved or conditionally approved
indications.
If in vitro data for antimicrobial new
animal drugs are included in this
section of full prescribing information
and the data have not been correlated to
clinical effectiveness, then such in vitro
data would be required to be
immediately preceded by the following
statement: ‘‘The following in vitro data
are available, but their clinical
significance is unknown.’’ See proposed
§ 201.405(a)(15).
p. ‘‘Target Animal Safety.’’ The
proposed rule would require this
section of full prescribing information to
have the heading ‘‘Target Animal
Safety,’’ followed by a summary of the
basis for the conclusion that the new
animal drug is safe in the target
animal(s) when used as approved or
conditionally approved (see proposed
§ 201.405(a)(16)).
q. ‘‘Effectiveness.’’ The proposed rule
would require this section of full
prescribing information to have the
heading ‘‘Effectiveness,’’ followed by a
summary of the basis for the conclusion
that the new animal drug is effective in
the target animal(s) when used as
approved. For conditionally approved
drugs, the ‘‘Effectiveness’’ section of full
prescribing information would be
required to include a summary of the
basis for the reasonable expectation of
effectiveness (see proposed
§ 201.405(a)(17)).
r. ‘‘Net Contents.’’ The proposed rule
would require this section of full
prescribing information, when
presented on the secondary container
labeling, to have the heading ‘‘Net
Contents,’’ followed by the contents of
the secondary container. The proposed
rule would exclude a ‘‘Net Contents’’
section from package inserts (see
proposed § 201.405(a)(18)).
s. ‘‘How Supplied.’’ The proposed rule
would require this section of full
prescribing information to have the
heading ‘‘How Supplied,’’ followed by
information on available drug strengths,
concentrations, and container sizes to
which the labeling applies. The
information in this section would be
required to be revised if new strengths,
concentrations, or container sizes are
added (see proposed § 201.405(a)(19)).
t. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of full prescribing information to
have the heading ‘‘Storage, Handling,
and Disposal’’ (see proposed
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§ 201.405(a)(20)). Drug storage
information would be included in this
section and may include, for example,
required temperature, humidity, and/or
light exposure conditions to maintain
the potency of the Rx new animal drug
until its established expiration date.
Also, any handling and drug disposal
information that we determine to be
necessary for safe and effective use of
the Rx new animal drug would be
included in this section. Handling
information may include, for example,
recommendations to reseal reusable
bottles promptly after opening and
conditions necessary to maintain
potency of reconstituted new animal
drugs. Drug disposal information may
include, for example, instructions on
disposal of unused portions of new
animal drugs remaining after treatment,
as well as used needles and/or syringes.
u. NADA/ANADA approval
statement. In accordance with section
502(w)(3) of the FD&C Act, by no later
than September 30, 2023, approved new
animal drugs must include the
following statement on labeling:
‘‘Approved by FDA under NADA # xxx–
xxx’’. By no later than September 30,
2023, approved generic Rx new animal
drugs must include the following
statement on labeling: ‘‘Approved by
FDA under ANADA # xxx–xxx’’. For
approved Rx new animal drugs, the
proposed rule would require this
section of full prescribing information to
include the ‘‘NADA approval
statement,’’ indicating the product’s
NADA number and that it was approved
by FDA. For approved generic Rx new
animal drugs that would be covered by
these regulations (i.e., those that
reference an NADA that has been
withdrawn for reasons other than safety
or effectiveness or under section 512(e)
of the FD&C Act and the ANADA’s
approval was not affected by the
withdrawal), the proposed rule would
require this section of full prescribing
information to include the ‘‘ANADA
approval statement.’’ The proposed rule
would establish format requirements for
the approval statement and would
require that the approval statement not
be so prominent as to obscure other
required information. The approval
statement could not be incorporated
into a seal, stamp, logo, or graphic. See
proposed § 201.405(a)(21).
v. Name and place of business. The
proposed rule would require this
section of full prescribing information to
identify the name and place of business
of the manufacturer, packer, or
distributor (see proposed
§ 201.405(a)(22)).
w. ‘‘Lot Number and Expiration
Date.’’ The proposed rule would require
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this section of full prescribing
information when provided on the
secondary container labeling. Package
inserts are excluded from this
requirement because they might apply
to multiple lots of secondary or
immediate containers of the Rx new
animal drug. When full prescribing
information is provided on the
secondary container labeling, this
section would be required to have the
heading ‘‘Lot Number and Expiration
Date,’’ followed by the identifying lot or
control number of the Rx new animal
drug within the secondary container
(see proposed § 201.405(a)(23)). Should
a problem be reported to FDA, a lot or
control number would help us more
easily to identify and trace back a
specific lot of a product. The proposed
rule would also require this section to
include the expiration date of the Rx
new animal drug within the secondary
container, in accordance with § 201.17
(21 CFR 201.17). An expiration date
better ensures that the new animal drug
would not be used after it expires.
Alternatively, the proposed rule
would allow for this section of full
prescribing information to refer to the
location on the secondary container
labeling or secondary container where
the lot or control number and expiration
date are printed (see proposed
§ 201.405(a)(23)). As an example, if the
lot number and expiration date are
printed on the bottom flap of a
secondary container, then the secondary
container labeling may state in this
section, ‘‘See carton bottom flap for lot
number and expiration date.’’ However,
in accordance with § 201.17, the
proposed rule would allow an
expiration date to be excluded from the
secondary container labeling or
secondary container if the expiration
date provided on the label or immediate
container is easily legible through the
secondary container.
x. ‘‘Revision Date.’’ The proposed rule
would require this section of full
prescribing information to have the
heading ‘‘Revision Date,’’ followed by
the date of the most recent revision of
the component of labeling that provides
full prescribing information, listing the
month followed by the year (see
proposed § 201.405(a)(24)). This
information is important to ensure that
the most current approved version of
the labeling is being used.
2. Prescription New Animal Drug Label
(Rx Label) (Proposed § 201.405(b))
The proposed rule would establish
content and format requirements for the
information presented on the label for
approved or conditionally approved Rx
new animal drugs (Rx label) (see
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proposed § 201.405(b)). As defined in
proposed § 201.403, ‘‘label’’ has the
same meaning as given in section 201(k)
of the FD&C Act, which defines the term
‘‘label’’ to mean a display of written,
printed, or graphic matter upon the
immediate container of any article. As
defined in proposed § 201.403, the
immediate container means the
container in contact with the new
animal drug, and it excludes package
liners.
Proposed § 201.405(b) would apply to
Rx labels that are of adequate size to
contain the proposed required
information per that paragraph, whereas
proposed § 201.405(c) would apply to
small labels for Rx new animal drugs
that are not of adequate size to contain
all the proposed required information in
proposed § 201.405(b).
Prescription new animal drugs labels
to which § 201.405(b) would apply may
consist of a single panel, a front panel
and one side or back panel, or a front
panel and multiple side and/or back
panels, and the proposed rule would
provide for such label designs (see
§ 201.405(b)). For Rx labels with a front
panel and one side or back panel, the
proposed rule would require certain
information for the front panel (see
proposed § 201.405(b)(1)), and the side
or back panel (see proposed
§ 201.405(b)(2)). For Rx labels consisting
of a single panel, the proposed rule
would require the information
identified in proposed § 201.405(b)(1)
followed by the information identified
in proposed § 201.405(b)(2), in order, on
the single panel. For Rx labels with a
front panel and multiple side and/or
back panels, the information identified
in proposed § 201.405(b)(1) followed by
the information identified in proposed
§ 201.405(b)(2) would be required in
order, starting on the front panel,
continuing on the panel immediately to
the right of the front panel, and
continuing to fill the panels to the right
until all of the information in proposed
§ 201.405(b)(1) and (b)(2) was presented.
In all instances, the information
proposed in § 201.405(b)(2)(iii) and (iv),
i.e., ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’ and ‘‘Inactive Ingredients,’’
would need to appear on the same
panel.
a. Front panel. The proposed rule
would require the following information
to be presented on the front panel of the
Rx label for an approved or
conditionally approved Rx new animal
drug and in the following order. Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information.
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i. Drug product identification. The
proposed rule would require this
section of the Rx label to include drug
product identification information (see
proposed § 201.405(b)(1)(i)). This
information may help the user quickly
and correctly identify the product and
distinguish it from other, similar
products. The information included in
this section of the Rx label would
include the same information as that in
the drug product identification section
of full prescribing information, as
described in proposed § 201.405(a)(1),
in addition to a statement that the drug
product is sterile, if applicable. Full
prescribing information would require a
drug product identification section and
a ‘‘Description’’ section. Full prescribing
information for sterile Rx new animal
drugs would be required to identify in
the ‘‘Description’’ section that the drug
is sterile. However, due to space
limitations, no ‘‘Description’’ section is
proposed for the Rx label. Instead, the
drug product identification section of
the Rx label for sterile Rx new animal
drugs would be required to state that the
drug product is sterile. See proposed
§ 201.405(b)(1)(i).
ii. Prescription statement. The
proposed rule would require this
section of the Rx label to include the
prescription statement (see proposed
§ 201.405(b)(1)(ii)). In accordance with
section 503(f)(4) of the FD&C Act, all Rx
new animal drugs must state on the
label: ‘‘Caution: Federal law restricts
this drug to use by or on the order of
a licensed veterinarian.’’
iii. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the Rx label to include a
conditional approval statement, as
described in proposed § 201.405(a)(3)
for full prescribing information (see
proposed § 201.405(b)(1)(iii)).
iv. Boxed warnings. For approved or
conditionally approved Rx new animal
drugs requiring boxed warnings, the
proposed rule would require this
section of the Rx label to include the
boxed warnings, as described in
proposed § 201.405(a)(4) for full
prescribing information (see proposed
§ 201.405(b)(1)(iv)).
v. ‘‘Indications for Use.’’ The
proposed rule would require this
section of the Rx label to have the
heading ‘‘Indications for Use,’’ followed
by the ‘‘Indications for Use’’ section, as
described in proposed § 201.405(a)(7)
for full prescribing information. If we
determine that there is insufficient
space on the Rx label for the complete
‘‘Indications for Use’’ section as
described in proposed § 201.405(a)(7),
then the proposed rule would require
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the sponsor to include in this section of
the Rx label the statement required in
proposed § 201.405(a)(7)(i), i.e., ‘‘For
[indication(s)] in [target animal(s)]’’. If
there is insufficient space on the Rx
label for the statement in proposed
§ 201.405(a)(7)(i), then an abbreviated
version of the statement would be
required: ‘‘For [abbreviated
indication(s)] in [target animal(s)]’’. In
either situation where there is
insufficient space on the Rx label for the
complete ‘‘Indications for Use’’ section
as specified in proposed § 201.405(a)(7),
the required statement would be
followed by one of the following
statements: ‘‘See package insert for
complete ‘Indications for Use’ ’’ if full
prescribing information is provided on
a package insert; or ‘‘See package
labeling for complete ‘Indications for
Use’ ’’ if full prescribing information is
provided on the secondary container
labeling. See proposed
§ 201.405(b)(1)(v).
The complete ‘‘Indications for Use’’
section as described in proposed
§ 201.405(a)(7) may exceed the available
space on the Rx label if, for example, it
includes specific conditions of use
(proposed § 201.405(a)(7)(ii)) or animals
for which the new animal drug is not
approved or conditionally approved
(proposed § 201.405(a)(7)(iii)), and/or
the indication(s) is lengthy and/or
complex. For example, a new animal
drug approved to treat and control
multiple species of roundworms,
lungworms, lice, and mites in beef cattle
would ordinarily identify all of those
species in the ‘‘Indications for Use’’
section of the label. However, if space
is insufficient on the Rx label to provide
the identity of all of the species of the
roundworms, lungworms, lice, and
mites for which the drug is effective, an
acceptable ‘‘abbreviated’’ version of the
‘‘Indications for Use’’ section on the Rx
label for this product might include, for
example, ‘‘For treatment and control of
certain species of roundworms,
lungworms, lice, and mites in beef
cattle. See package insert for complete
‘Indications for Use’.’’
vi. Extralabel use prohibition
statement. For approved Rx new animal
drugs prohibited from extralabel use, in
accordance with § 530.41, the proposed
rule would require this section of the Rx
label to include the extralabel use
prohibition statement, as described in
proposed § 201.405(a)(5) for full
prescribing information (see proposed
§ 201.405(b)(1)(vi)).
vii. ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods.’’
For new animal drugs approved or
conditionally approved for use in foodproducing animals, the proposed rule
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would require this section of the Rx
label to have the heading ‘‘Withdrawal
Periods and Residue Warnings’’ or
‘‘Withdrawal Periods,’’ followed by all
human food safety warnings, including
milk discard times, withdrawal periods,
and residue warning statements, as
described in proposed
§ 201.405(a)(10)(i) for full prescribing
information. If there is insufficient
space on the front panel of Rx labels
with only a front panel and one side or
back panel, the proposed rule would
require this section to be provided on
the side or back panel of the Rx label
immediately following the full
prescribing information statement
specified in proposed § 201.405(b)(2)(i).
See proposed § 201.405(b)(1)(vii).
viii. ‘‘Net Contents.’’ The proposed
rule would require this section of the Rx
label to have the heading ‘‘Net
Contents,’’ followed by the contents of
the immediate container, in accordance
with § 201.51 (see proposed
§ 201.405(b)(1)(viii)).
ix. NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the proposed rule would require
this section of the Rx label to include
the NADA or ANADA approval
statement, as described in proposed
§ 201.405(a)(21) for full prescribing
information (see proposed
§ 201.405(b)(1)(ix)).
b. Side or back panel. The proposed
rule would require the following
information to be presented on the side
or back panel of the Rx label for an
approved or conditionally approved Rx
new animal drug in the following order
(see proposed § 201.405(b)(2)). Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information.
i. Full prescribing information
statement. The proposed rule would
require this section of the Rx label to
include one of two statements (see
proposed § 201.405(b)(2)(i)). If full
prescribing information is provided on
the package insert, the following
statement would be used: ‘‘Before using
this drug, read package insert for full
prescribing information.’’ If full
prescribing information is provided on
the secondary container labeling, the
following statement would be used:
‘‘Before using this drug, read package
labeling for full prescribing
information.’’ Because full prescribing
information would not be provided on
the Rx label, the purpose of the
statements would be to remind the
veterinarian to read full prescribing
information before using the Rx new
animal drug.
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ii. ‘‘Dosage and Administration.’’ The
proposed rule would require this
section of the Rx label to have the
heading ‘‘Dosage and Administration,’’
followed by the ‘‘Dosage and
Administration’’ section, as described in
proposed § 201.405(a)(8) for full
prescribing information. If there is
insufficient space on the Rx label for the
complete requirements as specified in
proposed § 201.405(a)(8), or if it is
necessary for additional information
provided in full prescribing information
that is not provided on the Rx label to
be read before administering the drug
(e.g., complete warnings and
precautions, contraindications, and/or
target animal safety), then FDA may
exclude this section from the Rx label
(see proposed § 201.405(b)(2)(ii)). For
example, with respect to the latter
situation, if careful observation of the
animal after dosing is advised to watch
for adverse reactions, this information
typically would be described in the
‘‘Animal Safety Warnings and
Precautions’’ subsection, which would
not be required on the Rx label but
would be required on full prescribing
information. Excluding the ‘‘Dosage and
Administration’’ section from the Rx
label in this situation helps to ensure
that the veterinarian would read full
prescribing information, which would
include the ‘‘Dosage and
Administration’’ section as well as the
‘‘Animal Safety Warnings and
Precautions’’ subsection, before treating
the animal. Users would also be
reminded to read full prescribing
information before using the drug via
the full prescribing information
statement that would be required in the
previous section of the Rx label by
proposed § 201.405(b)(2)(i).
iii. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the Rx label to
have the heading ‘‘Active Ingredient’’ or
‘‘Active Ingredients,’’ followed by the
established name and strength or
concentration of each active ingredient.
If the Rx new animal drug contains one
active ingredient, the proposed rule
would require this section of the Rx
label to be entitled ‘‘Active Ingredient.’’
If the Rx new animal drug contains
more than one active ingredient, the
proposed rule would require this
section of the Rx label to be entitled
‘‘Active Ingredients.’’ The requirement
to provide established name and
strength or concentration of each active
ingredient on the Rx label would be
consistent with the requirement for the
established name and quantity or
proportion of each active ingredient on
the label of prescription drugs, in
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accordance with section 502(e)(1)(A)(ii),
(B), and (g) of the FD&C Act (see
proposed § 201.405(b)(2)(iii)). This
information is currently required to be
on the label for Rx animal drugs, in
accordance with § 201.105(b)(4).
Proposed § 201.405(b) and (c) would
establish the content and format
requirements for the label for approved
or conditionally approved Rx new
animal drugs and would replace the
requirements for the label of approved
or conditionally approved Rx new
animal drugs currently provided in
§ 201.105(b). Furthermore, § 201.105
would be amended to refer to proposed
§ 201.405 for the content and format
requirements for labeling components
for approved or conditionally approved
Rx new animal drugs.
iv. ‘‘Inactive Ingredients.’’ The
proposed rule would require this
section of the Rx label to have the
heading ‘‘Inactive Ingredients,’’
followed by the established name of
each inactive ingredient, as described in
proposed § 201.405(a)(6)(viii) for full
prescribing information (see proposed
§ 201.405(b)(2)(iv)).
v. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the Rx label to have the
heading ‘‘Storage, Handling, and
Disposal,’’ followed by drug storage,
handling, and disposal information, as
described in proposed § 201.405(a)(20)
for full prescribing information (see
proposed § 201.405(b)(2)(v)).
vi. Name and place of business. The
proposed rule would require this
section of the Rx label to identify the
name and place of business of the
manufacturer, packer, or distributor, as
required in section 502(b) of the FD&C
Act (see proposed § 201.405(b)(2)(vi)).
vii. ‘‘Lot Number and Expiration
Date’’ or ‘‘Lot Number.’’ The proposed
rule would require this section of the Rx
label to have the heading ‘‘Lot Number
and Expiration Date’’ or ‘‘Lot Number,’’
followed by the identifying lot or
control number of the Rx new animal
drug within the immediate container
(see proposed § 201.405(b)(2)(vii)). A lot
or control number would allow us to
more easily identify and trace back a
specific lot of a product should a
problem be reported to FDA. We would
also require this section of the Rx label
to include the expiration date of the Rx
new animal drug within the immediate
container, in accordance with § 201.17.
An expiration date on the Rx label
better ensures that the new animal drug
would not be used after it expires.
Alternatively, the proposed rule would
allow for this section to refer to the
location on the Rx label or immediate
container where the lot or control
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number and expiration date are printed
(see proposed § 201.405(b)(2)(vii)). As
an example, if the lot number and
expiration date are printed at the top of
the immediate container, then the Rx
label may state in this section, ‘‘See top
of container for lot number and
expiration date.’’ If the immediate
container provides a single dose of the
Rx new animal drug and is packaged
individually in a secondary container
that provides an expiration date on the
secondary container labeling or
secondary container, the proposed rule
would not require an expiration date on
the Rx label or immediate container, in
accordance with § 201.17. Under such
provision, this section of the Rx label
would be required to be entitled ‘‘Lot
Number.’’
viii. ‘‘Revision Date.’’ The proposed
rule would require the last section of the
Rx label to have the heading ‘‘Revision
Date,’’ followed by the date of the most
recent revision of the Rx label, listing
the month followed by the year (see
proposed § 201.405(b)(2)(viii)).
3. Prescription New Animal Drug Small
Label (Rx Small Label) (Proposed
§ 201.405(c))
The proposed rule would establish
content and format requirements for the
small label for Rx new animal drugs (Rx
small label) (see proposed § 201.405(c)).
Some immediate containers, such as
blister packs, pre-filled syringes, and
small vials, are so small that only a
minimal amount of information can be
included on their label. The proposed
rule would establish requirements for
Rx small labels for approved or
conditionally approved Rx new animal
drugs (see proposed § 201.405(c)). We
recognize that the size of the label is
dependent upon the size of the
immediate container. If an immediate
container lacks sufficient space to
contain a label that accommodates all of
the information required by proposed
§ 201.405(b), the requirements of
proposed § 201.405(c) would instead
apply. We would ordinarily make this
determination during the review of the
new animal drug and its labeling, taking
into consideration the readability and
legibility of the information.
The proposed rule would require the
following information to be presented
on the Rx small label for an approved
or conditionally approved Rx new
animal drug and in the following order
(see proposed § 201.405(c)).
a. Proprietary name of the finished
drug product. The proposed rule would
require this section of the Rx small label
to include the proprietary name of the
finished drug product (see proposed
§ 201.405(c)(1)). This requirement
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already exists for small labels for drugs
in general in § 201.10(i)(1), but is
repeated in these proposed regulations
to include all requirements for labeling
of approved or conditionally approved
new animal drugs in proposed subpart
H.
b. Established name of the drug
product. The proposed rule would
require this section of the Rx small label
to include the established name of the
drug product (see proposed
§ 201.405(c)(2)). This requirement
already exists for small labels for drugs
in general in § 201.10(i)(1), but is
repeated in these proposed regulations
to include all requirements for labeling
of approved or conditionally approved
new animal drugs in proposed subpart
H.
c. Active ingredient(s). The proposed
rule would require this section of the Rx
small label to include the established
name and strength or concentration of
each active ingredient, which is
consistent with the requirement for the
established name and quantity or
proportion of each active ingredient on
the label of prescription drugs, in
accordance with section 502(e)(1)(A)(ii),
(B), and (g) of the FD&C Act (see
proposed § 201.405(c)(3)). This
information is currently required to be
on the label for Rx animal drugs, in
accordance with § 201.105(b)(4).
Proposed § 201.405(b) and (c) would
establish the content and format
requirements for the label for approved
or conditionally approved Rx new
animal drugs and would replace the
requirements for the label of approved
or conditionally approved Rx new
animal drugs currently provided in
§ 201.105(b). Furthermore, § 201.105
would be amended to cross-reference
proposed § 201.405 for the content and
format requirements for labeling
components for approved or
conditionally approved Rx new animal
drugs (see discussion in section V.I.).
d. Controlled substance symbol. For
Rx new animal drugs that are controlled
substances, the proposed rule would
require this section of the Rx small label
to include the controlled substance
schedule symbol in accordance with
part 1302 designating the schedule for
the drug substance (see proposed
§ 201.405(c)(4)).
e. Prescription statement. The
proposed rule would require this
section of the Rx small label to state:
‘‘Rx Animal Use’’ (see proposed
§ 201.405(c)(5)). In accordance with
section 503(f)(4) of the FD&C Act, the
label for all Rx new animal drugs must
include the following statement:
‘‘Caution: Federal law restricts this drug
to use by or on the order of a licensed
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veterinarian.’’ However, since 1960 (25
FR 12592) § 201.105(b)(6) exempts
‘‘containers too small or otherwise
unable to accommodate a label with
sufficient space’’ to include the full
prescription statement provided that the
full statement may be placed on the
outer container only. We are proposing
the ‘‘Rx Animal Use’’ statement for a Rx
small label for Rx new animal drugs.
This statement would appropriately
identify the Rx status of the new animal
drug and would require minimal space.
f. ‘‘For [target animal(s)] only.’’ The
proposed rule would require this
section of the Rx small label to include
a brief listing of the approved target
animal(s) as follows: ‘‘For [target
animal(s)] only’’ (see proposed
§ 201.405(c)(6)). The brief listing of the
approved target animal(s) would be
used in place of full ‘‘Indications for
Use’’ information because Rx small
labels lack sufficient space. This listing
would not require as much space on the
Rx small label.
g. Full prescribing information
statement. The proposed rule would
require this section of the Rx small label
to include one of two statements. If full
prescribing information is provided on
the package insert, the following
statement would be used: ‘‘Read
package insert for full prescribing
information.’’ If full prescribing
information is provided on the
secondary container labeling, the
following statement would be used:
‘‘Read package labeling for full
prescribing information.’’ See proposed
§ 201.405(c)(7). Because full prescribing
information would not be provided on
the Rx small label, the purpose of the
statements would be to remind the
veterinarian to read full prescribing
information before using the Rx new
animal drug.
h. ‘‘Net Contents.’’ The proposed rule
would require this section of the Rx
small label to have the heading ‘‘Net
Contents,’’ followed by the contents of
the immediate container, in accordance
with § 201.51 (see proposed
§ 201.405(c)(8)).
i. Name and place of business. The
proposed rule would require this
section of the Rx small label to identify
the name and place of business of the
manufacturer, packer, or distributor, as
required in section 502(b) of the FD&C
Act (see proposed § 201.405(c)(9)).
j. ‘‘Lot, Exp. and Storage’’ or ‘‘Lot and
Storage.’’ The proposed rule would
require this section of the Rx small label
to have the heading ‘‘Lot, Exp. and
Storage’’ or ‘‘Lot and Storage,’’ followed
by the identifying lot or control number
of the Rx new animal drug within the
immediate container (see proposed
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§ 201.405(c)(10)). Should a problem be
reported to FDA, a lot or control number
would allow us more easily to identify
and trace back a specific lot of a
product. We would also require this
section of the Rx small label to include
the expiration date of the Rx new
animal drug within the immediate
container, in accordance with § 201.17.
An expiration date on the Rx small label
better ensures that the new animal drug
would not be used after it expires.
The proposed rule would also require
this section of the Rx small label to
include drug storage information for the
new animal drug (see proposed
§ 201.405(c)(10)). Storage information is
necessary to maintain potency of the
drug before its expiration date.
Requiring this information on the Rx
small label is needed for safe and
effective use of new animal drugs. If the
immediate container provides a single
dose of the Rx new animal drug and is
packaged individually in a secondary
container that provides an expiration
date on the secondary container labeling
or secondary container, the proposed
rule would not require an expiration
date on the Rx small label or immediate
container, in accordance with § 201.17.
Under such provision, this section of
the Rx small label would be required to
be entitled ‘‘Lot and Storage.’’
k. ‘‘Revision Date.’’ The proposed rule
would require this section of the Rx
small label to have the heading
‘‘Revision Date,’’ followed by the date of
the most recent revision of the Rx small
label, listing the month followed by the
year (see proposed § 201.405(c)(11)).
4. Labeling for Secondary Containers for
Rx New Animal Drugs That Include a
Package Insert (Rx Secondary Container
Labeling) (Proposed § 201.405(d))
The proposed rule would establish
content and format requirements for the
information on the labeling for
secondary containers of approved or
conditionally approved Rx new animal
drugs that include a package insert (Rx
secondary container labeling) (see
proposed § 201.405(d)). In this situation,
the package insert would be required to
include full prescribing information, as
described in proposed § 201.405(a).
In accordance with section 201(k) of
the FD&C Act, the Rx secondary
container labeling could exclude any
information described in proposed
§ 201.405(d) that would be required to
appear on the Rx label or Rx small label
(see proposed § 201.405(b) or (c),
respectively) if such information on the
Rx label or Rx small label was easily
legible through the secondary container.
The Rx secondary container labeling
to which proposed § 201.405(d) would
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apply may consist of a front panel and
one side or back panel, or a front panel
and multiple side and/or back panels.
Proposed § 201.405(d) would provide
for such Rx secondary container
labeling designs. For Rx secondary
container labeling with a front panel
and one side or back panel, proposed
§ 201.405(d)(1) would provide required
information for the front panel, and
proposed § 201.405(d)(2) would provide
required information for the side or back
panel. For Rx secondary container
labeling with a front panel and multiple
side and/or back panels, the information
identified in proposed § 201.405(d)(1)
followed by the information identified
in proposed § 201.405(d)(2) would be
required in order, starting on the front
panel, continuing on the panel
immediately to the right of the front
panel, and continuing to fill the panels
to the right until all of the information
in proposed § 201.405(d)(1) and (d)(2)
was presented. In all instances, the
information proposed in
§ 201.405(d)(2)(v) and (vi), i.e., ‘‘Active
Ingredient’’ or ‘‘Active Ingredients’’ and
‘‘Inactive Ingredients,’’ would need to
appear on the same panel.
a. Front panel. The proposed rule
would require the following information
to be presented on the front panel of the
Rx secondary container labeling and in
the following order (see proposed
§ 201.405(d)(1)). Unless otherwise
indicated, this information would be the
same as that required by proposed
§ 201.405(a) for full prescribing
information.
i. Drug product identification. The
proposed rule would require this
section of the Rx secondary container
labeling to include drug product
identification (see proposed
§ 201.405(d)(1)(i)). The information
would be the same as that included in
the drug product identification section
for full prescribing information, as
described in proposed § 201.405(a)(1),
and would also identify if the drug
product is sterile. Full prescribing
information would require a drug
product identification section and a
‘‘Description’’ section. Full prescribing
information for sterile Rx new animal
drugs would be required to identify in
the ‘‘Description’’ section that the drug
is sterile. However, due to space
limitations, no ‘‘Description’’ section
would be required on the Rx secondary
container labeling. Instead, the drug
product identification section of the Rx
secondary container labeling for sterile
Rx new animal drugs would be required
to state that the drug is sterile.
ii. Prescription statement. The
proposed rule would require this
section of the Rx secondary container
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labeling to include the prescription
statement, as described in proposed
§ 201.405(a)(2) for full prescribing
information (see proposed
§ 201.405(d)(1)(ii)).
iii. Conditional approval statement.
For conditionally approved Rx new
animal drugs, the proposed rule would
require this section of the Rx secondary
container labeling to include a
conditional approval statement, as
described in proposed § 201.405(a)(3)
for full prescribing information (see
proposed § 201.405(d)(1)(iii)).
iv. Boxed warnings. For approved or
conditionally approved Rx new animal
drugs requiring boxed warnings, the
proposed rule would require this
section of the Rx secondary container
labeling to include the boxed warnings,
as described in proposed § 201.405(a)(4)
for full prescribing information (see
proposed § 201.405(d)(1)(iv)).
v. ‘‘Indications for Use.’’ The
proposed rule would require this
section of the Rx secondary container
labeling to have the heading
‘‘Indications for Use,’’ followed by the
‘‘Indications for Use’’ section, as
described in proposed § 201.405(a)(7)
for full prescribing information (see
proposed § 201.405(d)(1)(v)).
vi. Extralabel prohibition statement.
For approved new animal drugs
prohibited from extralabel use, in
accordance with § 530.41, the proposed
rule would require this section of the Rx
secondary container labeling to include
the extralabel use prohibition statement,
as described in proposed § 201.405(a)(5)
for full prescribing information (see
proposed § 201.405(d)(1)(vi)).
vii. ‘‘Net Contents.’’ The proposed
rule would require this section of the Rx
secondary container labeling to have the
heading ‘‘Net Contents,’’ followed by
the contents of the secondary container
(see proposed § 201.405(d)(1)(vii)).
viii. NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the proposed rule would require
this section of the Rx secondary
container labeling to include the NADA
or ANADA approval statement, as
described in proposed § 201.405(a)(21)
for full prescribing information (see
proposed § 201.405(d)(1)(viii)).
b. Side or back panel. The proposed
rule would require the following
information to be presented on the side
or back panel of the Rx secondary
container labeling and in the following
order (see proposed § 201.405(d)(2)).
Unless otherwise indicated, this
information would be the same as that
required by proposed § 201.405(a) for
full prescribing information.
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i. Full prescribing information
statement. The proposed rule would
require this section of the Rx secondary
container labeling to include the
statement: ‘‘Before using this drug, read
package insert for full prescribing
information’’ (see proposed
§ 201.405(d)(2)(i)). Because full
prescribing information would not be
provided on the Rx secondary container
labeling, the purpose of the full
prescribing information statement
would be to remind the veterinarian to
read full prescribing information before
using the Rx new animal drug.
ii. ‘‘Dosage and Administration.’’ The
proposed rule would require this
section of the Rx secondary container
labeling to have the heading ‘‘Dosage
and Administration,’’ followed by the
‘‘Dosage and Administration’’ section,
as described in proposed § 201.405(a)(8)
for full prescribing information (see
proposed § 201.405(d)(2)(ii)).
iii. ‘‘Contraindications.’’ The
proposed rule would require this
section of the Rx secondary container
labeling to have the heading
‘‘Contraindications,’’ followed by the
‘‘Contraindications’’ section, as
described in proposed § 201.405(a)(9)
for full prescribing information (see
proposed § 201.405(d)(2)(iii)).
iv. ‘‘Warnings and Precautions.’’ The
proposed rule would require this
section of the Rx secondary container
labeling to have the heading ‘‘Warnings
and Precautions,’’ followed by the
‘‘Warnings and Precautions’’ section, as
described in proposed § 201.405(a)(10)
for full prescribing information (see
proposed § 201.405(d)(2)(iv)).
v. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the Rx secondary
container labeling to have the heading
‘‘Active Ingredient’’ or ‘‘Active
Ingredients,’’ followed by the
established name and strength or
concentration of each active ingredient,
as described in proposed
§ 201.405(b)(2)(iii) for the Rx label (see
proposed § 201.405(d)(2)(v)).
vi. ‘‘Inactive Ingredients.’’ The
proposed rule would require this
section of the Rx secondary container
labeling to have the heading ‘‘Inactive
Ingredients,’’ followed by the
established name of each inactive
ingredient, as described in proposed
§ 201.405(a)(6)(viii) for full prescribing
information (see proposed
§ 201.405(d)(2)(vi)).
vii. ‘‘Storage, Handling, and
Disposal.’’ The proposed rule would
require this section of the Rx secondary
container labeling to have the heading
‘‘Storage, Handling, and Disposal,’’
followed by drug storage, handling, and
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disposal information, as described in
proposed § 201.405(a)(20) for full
prescribing information (see proposed
§ 201.405(d)(2)(vii)).
viii. Name and place of business. The
proposed rule would require this
section of the Rx secondary container
labeling to identify the manufacturer,
packer, or distributor, as described in
proposed § 201.405(a)(22) for full
prescribing information (see proposed
§ 201.405(d)(2)(viii)).
ix. ‘‘Lot Number and Expiration
Date.’’ The proposed rule would require
this section of the Rx secondary
container labeling to have the heading
‘‘Lot Number and Expiration Date,’’
followed by the identifying lot or
control number of the Rx new animal
drug within the secondary container.
The proposed rule would also require
this section of the Rx secondary
container labeling to include the
expiration date of the Rx new animal
drug within the secondary container, in
accordance with § 201.17. Alternatively,
the proposed rule would allow for this
section to refer to the location on the Rx
secondary container labeling or
secondary container where the lot or
control number and expiration date are
printed (see proposed
§ 201.405(d)(2)(ix)). As an example, if
the lot number and expiration date are
printed on the bottom flap of a
secondary container, then the labeling
may state in this section, ‘‘See carton
bottom flap for lot number and
expiration date. However, in accordance
with § 201.17, the proposed rule would
allow an expiration date to be excluded
from the Rx secondary container
labeling or secondary container if the
expiration date provided on the Rx
label, Rx small label, or immediate
container is easily legible through the
secondary container.
x. ‘‘Revision Date.’’ The proposed rule
would require this section of the Rx
secondary container labeling to have the
heading ‘‘Revision Date,’’ followed by
the date of the most recent revision of
the Rx secondary container labeling,
listing the month followed by the year
(see proposed § 201.405(d)(2)(x)).
5. Shipping Labeling for Rx New
Animal Drugs (Rx Shipping Labeling)
(Proposed § 201.405(e))
The proposed rule would establish
content and format requirements for the
information on the shipping labeling for
approved or conditionally approved Rx
new animal drugs (Rx shipping
labeling). As defined in proposed
§ 201.403, shipping labeling is
associated with the outermost carton
containing immediate containers,
secondary containers, and/or multiple
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unit (multi-unit) cartons of a new
animal drug and intended for shipment,
but not display, of the product. The
proposed rule would require the Rx
shipping labeling to include, among
additional information, drug product
identity, the manufacturer, packer, or
distributor, and drug storage and
handling conditions (see proposed
§ 201.405(e)). However, the Rx shipping
labeling for controlled substances would
not include information that would
identify the drug, in accordance with
§ 1301.74(e), to guard against storage or
in-transit losses due to theft or
diversion.
The proposed rule would require the
following information to be presented
on the Rx shipping labeling and in the
following order (see proposed
§ 201.405(e)). Unless otherwise
indicated, this information would be the
same as that required by proposed
§ 201.405(a) for full prescribing
information.
a. Proprietary name of the finished
drug product. The proposed rule would
require this section of the Rx shipping
labeling to include the proprietary name
of the finished drug product (see
proposed § 201.405(e)(1)). This section
would be excluded from the Rx
shipping labeling for a controlled
substance.
b. Established name of the drug
product. The proposed rule would
require this section of the Rx shipping
labeling to include the established name
of the drug product (see proposed
§ 201.405(e)(2)). This section would be
excluded from the Rx shipping labeling
for a controlled substance.
c. Established name and strength or
concentration of each active ingredient.
The proposed rule would require this
section of the Rx shipping labeling to
provide the established name and
strength or concentration of each active
ingredient. This section would be
excluded from the Rx shipping labeling
for a controlled substance (see proposed
§ 201.405(e)(3)).
d. Conditional approval statement.
For conditionally approved Rx new
animal drugs, the proposed rule would
require this section of the Rx shipping
labeling to include a conditional
approval statement, as described in
proposed § 201.405(a)(3) for full
prescribing information (see proposed
§ 201.405(e)(4)). This section would be
excluded from the Rx shipping labeling
for a controlled substance.
e. ‘‘Net Contents.’’ The proposed rule
would require this section of the Rx
shipping labeling to have the heading
‘‘Net Contents,’’ followed by the
contents of the shipping carton (see
proposed § 201.405(e)(5)).
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f. ‘‘Storage and Handling.’’ The
proposed rule would require this
section of the Rx shipping labeling to
have the heading ‘‘Storage and
Handling,’’ followed by drug storage
information (see proposed
§ 201.405(e)(6)). Also, any handling
information required for safe and
effective use of the new animal drug
would be included in this section.
Information on disposal of the new
animal drug would not be required to be
included on the Rx shipping labeling.
g. NADA/ANADA approval statement.
For approved new animal drugs or
approved generic new animal drugs, the
proposed rule would require this
section of the Rx shipping labeling to
include the NADA or ANADA approval
statement, as described in proposed
§ 201.405(a)(21) for full prescribing
information (see proposed
§ 201.405(e)(7)). This section would be
excluded from the Rx shipping labeling
for a controlled substance.
h. Name and place of business. The
proposed rule would require this
section of the Rx shipping labeling to
identify the name and place of business
of the manufacturer, packer, or
distributor, as described in proposed
§ 201.405(a)(22) for full prescribing
information (see proposed
§ 201.405(e)(8)).
i. ‘‘Lot Number and Expiration Date.’’
The proposed rule would require this
section of the Rx shipping labeling to
have the heading ‘‘Lot Number and
Expiration Date,’’ followed by the
identifying lot or control number(s) and
the expiration date(s) of the Rx new
animal drug within the shipping carton
(see proposed § 201.405(e)(9)). The
shipping carton may contain more than
one lot of the new animal drug, and
therefore, more than one lot or control
number and expiration date may be
listed in this section of the Rx shipping
labeling.
j. ‘‘Revision Date.’’ The proposed rule
would require the last section of the Rx
shipping labeling to have the heading
‘‘Revision Date,’’ followed by the date of
the most recent revision of the Rx
shipping labeling, listing the month
followed by the year (see proposed
§ 201.405(e)(10)).
6. Other Approved Labeling for Rx New
Animal Drugs (Rx Other Approved
Labeling) (Proposed § 201.405(f))
The proposed rule would establish
content and format requirements for the
information presented on other
approved labeling for approved or
conditionally approved Rx new animal
drugs (Rx other approved labeling) (see
proposed § 201.405(f)). Rx other
approved labeling includes, but is not
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limited to, labeling on display cartons
and multi-unit cartons (excluding
shipping cartons), containing the
immediate containers or the secondary
containers of the Rx new animal drug.
The proposed rule would require the
following information to be presented
on the Rx other approved labeling and
in the following order (see proposed
§ 201.405(f)). Unless otherwise
indicated, this information would be the
same as required by proposed
§ 201.405(a) for full prescribing
information.
a. Proprietary name of the finished
drug product. The proposed rule would
require this section of the Rx other
approved labeling to include the
proprietary name of the finished drug
product (see proposed § 201.405(f)(1)).
b. Established name of the drug
product. The proposed rule would
require this section of the Rx other
approved labeling to include the
established name of the drug product
(see proposed § 201.405(f)(2)).
c. Established name and strength or
concentration of each active ingredient.
The proposed rule would require this
section of the Rx other approved
labeling to provide the established name
and strength or concentration of each
active ingredient (see proposed
§ 201.405(f)(3)).
d. Controlled substance symbol. The
proposed rule would require this
section of the Rx other approved
labeling for controlled substances to
include the controlled substance
schedule symbol, in accordance with
part 1302 designating the schedule for
the drug substance (see proposed
§ 201.405(f)(4)).
e. Prescription statement. The
proposed rule would require this
section of the Rx other approved
labeling to include the prescription
statement, as described in proposed
§ 201.405(a)(2) for full prescribing
information (see proposed
§ 201.405(f)(5)).
f. Conditional approval statement. For
conditionally approved new animal
drugs, the proposed rule would require
this section of the Rx other approved
labeling to include a conditional
approval statement, as described in
proposed § 201.405(a)(3) for full
prescribing information (see proposed
§ 201.405(f)(6)).
g. Boxed warnings. For approved or
conditionally approved Rx new animal
drugs requiring boxed warnings, the
proposed rule would require this
section of the Rx other approved
labeling to include the boxed warnings,
as described in proposed § 201.405(a)(4)
for full prescribing information (see
proposed § 201.405(f)(7)).
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h. Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use, in
accordance with § 530.41, the proposed
rule would require this section of the Rx
other approved labeling to include the
extralabel use prohibition statement, as
described in proposed § 201.405(a)(5)
for full prescribing information (see
proposed § 201.405(f)(8)).
i. ‘‘Net Contents.’’ The proposed rule
would require this section of the Rx
other approved labeling to have the
heading ‘‘Net Contents,’’ followed by
the contents of the container to which
the Rx other approved labeling applies
(see proposed § 201.405(f)(9)).
j. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the Rx other approved
labeling to have the heading ‘‘Storage,
Handling, and Disposal,’’ followed by
drug storage, handling, and disposal
information, as described in proposed
§ 201.405(a)(20) for full prescribing
information (see proposed
§ 201.405(f)(10)).
k. NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the proposed rule would require
this section of the Rx other approved
labeling to include the NADA or
ANADA approval statement, as
described in proposed § 201.405(a)(21)
for full prescribing information (see
proposed § 201.405(f)(11)).
l. Name and place of business. The
proposed rule would require this
section of the Rx other approved
labeling to identify the name and place
of business of the manufacturer, packer,
or distributor, as described in proposed
§ 201.405(a)(22) for full prescribing
information (see proposed
§ 201.405(f)(12)).
m. ‘‘Lot Number and Expiration
Date.’’ The proposed rule would require
this section of the Rx other approved
labeling to have the heading ‘‘Lot
Number and Expiration Date,’’ followed
by the identifying lot or control number
of the Rx new animal drug within the
container to which the Rx other
approved labeling applies. This section
of the Rx other approved labeling would
also be required to include the
expiration date of the Rx new animal
drug within the container to which the
Rx other approved labeling applies, in
accordance with § 201.17. In accordance
with § 201.17, the proposed rule would
allow an expiration date to be excluded
from the Rx other approved labeling if
the expiration date provided on
containers within or their labeling is
easily legible through the container to
which the Rx other approved labeling
applies (see proposed § 201.405(f)(13)).
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n. ‘‘Revision Date.’’ The proposed rule
would require the last section of the Rx
other approved labeling to have the
heading ‘‘Revision Date,’’ followed by
the date of the most recent revision of
the Rx other approved labeling, listing
the month followed by the year (see
proposed § 201.405(f)(14)).
E. Content and Format for Over-TheCounter (OTC) New Animal Drug
Labeling—Overview (Proposed
§ 201.407)
The proposed rules provides content
and format requirements for all
components of labeling for approved or
conditionally approved OTC new
animal drugs other than those for use in
animal feeds that are subject to part 558
(see proposed § 201.407). Proposed
§ 201.409 would establish the content
and format requirements for all
components of labeling for approved or
conditionally approved new animal
drugs intended for use in animal feeds
that are subject to part 558. OTC new
animal drugs are new animal drugs that
can be used without a prescription from
a veterinarian. They are intended for use
by the layperson, such as pet owners
and livestock producers. In accordance
with section 502(f) of the FD&C Act,
OTC drugs must bear adequate
directions for use on labeling. Adequate
directions for use means directions
under which the layperson can use a
drug safely and for the purposes for
which it is intended (see § 201.5).
The proposed rule would require that
labeling sections or subsections that do
not apply be omitted from the labeling
for approved or conditionally approved
OTC new animal drugs (see proposed
§ 201.407). For example, OTC new
animal drugs approved or conditionally
approved for use in non-food-producing
animals (e.g., cats, dogs) would not
require the labeling subsection entitled
either ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods’’.
FDA determines the final content of
each applicable section of labeling
during the review of each new animal
drug as part of the approval process.
The proposed rule would identify the
information that would be required to
be included on the labeling component
that would provide full product
information for OTC new animal drugs
in proposed § 201.407(a). Full product
information for OTC new animal drugs
would be similar in concept to full
prescribing information for Rx new
animal drugs in that it would include all
information necessary for the safe and
effective use of the OTC new animal
drug. Thus, all approved or
conditionally approved OTC new
animal drugs would be required to
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provide a labeling component that
includes full product information. If a
package insert is provided with an OTC
new animal drug, the proposed rule
would require the package insert to
include full product information. If only
partial information is provided on a
package insert, the user may mistakenly
assume the package insert includes
complete information on the safe and
effective use of the drug when in fact it
does not. If no package insert is
provided with an OTC new animal drug,
the secondary container labeling would
be required to include full product
information. If no package insert or
secondary container labeling is
provided with the OTC new animal
drug, then full product information
would need to be provided on the label
(see proposed § 201.407(a)).
The label is the labeling component
that appears on the immediate
container, which is the container in
contact with the drug. The proposed
rule would establish content and format
requirements for the label for an
approved or conditionally approved
OTC new animal drug that does not
provide full product information (see
proposed § 201.407(b)). The proposed
rule would establish content and format
requirements for a small label for an
approved or conditionally approved
OTC new animal drug that we
determine lacks sufficient space to
comply with proposed § 201.407(b) (see
proposed § 201.407(c)).
For purposes of proposed subpart H,
we would define a package insert for an
approved or conditionally approved
OTC new animal drug as a labeling
component that contains full product
information and is included with the
immediate container or secondary
container or is attached to the label (see
proposed § 201.403). Where the package
insert is attached to the label, which is
sometimes referred to as, for example,
‘‘extended labeling,’’ ‘‘onserts,’’ or
‘‘outserts,’’ for purposes of proposed
subpart H, the package insert providing
full product information and attached to
the label would need to comply with
proposed § 201.407(a). The label would
need to comply with proposed
§ 201.407(b) or (c), as applicable.
FDA considers the secondary
container for a new animal drug to be
the packaging that surrounds the
immediate container. The proposed rule
would establish content and format
requirements for secondary container
labeling for an approved or
conditionally approved OTC new
animal drug (see proposed § 201.407(d)).
If a package insert is provided with an
OTC new animal drug, then the
secondary container labeling would be
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required to comply with proposed
§ 201.407(d) and the package insert
would be required to provide full
product information to comply with
proposed § 201.407(a). If no package
insert is provided with an OTC new
animal drug, the proposed rule would
require full product information to
appear on the secondary container
labeling (see proposed § 201.407(a)).
In accordance with the definition of
‘‘label’’ in section 201(k) of the FD&C
Act, information on the label must also
appear on an outside container or
wrapper of the retail package, if it exists,
or be easily legible through the outside
container or wrapper. For purposes of
these proposed regulations, FDA
considers the secondary container to be
an ‘‘outside container or wrapper of the
retail package’’ for new animal drugs.
Therefore, if a secondary container
exists, the proposed rule would require
the secondary container labeling to
include all information that would be
on the label in accordance with
proposed § 201.407(b) or (c), unless the
information on the label is easily legible
through the secondary container (see
proposed § 201.407(a) or (d)).
Shipping labeling is associated with
the outermost carton containing a new
animal drug, which is intended for
shipping, but not displaying the
product. The proposed rule would
establish content and format
requirements for the shipping labeling
of approved or conditionally approved
OTC new animal drugs including a
requirement that such shipping labeling
identify the new animal drug, the
manufacturer, and drug storage and
handling information(see proposed
§ 201.407(e)).
Depending on how a sponsor intends
to sell or display an approved or
conditionally approved OTC new
animal drug, there may be other
containers such as display cartons and
multiple unit (multi-unit) cartons that
contain immediate containers or
secondary containers. These containers
may be packaged in shipping cartons.
The proposed rule would establish
content and format requirements for the
labeling of these other containers for
OTC new animal drugs (see proposed
§ 201.407(f)).
Labeling sections and subsections for
OTC new animal drugs would not be
numbered. Headings of sections and
subsections that would be required to
appear verbatim on labeling are
identified in the proposed regulations in
quotations. Similarly, certain other
labeling text would be required to
appear verbatim on labeling; this text is
also identified in the proposed
regulations in quotations.
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The proposed rule would require the
labeling of approved or conditionally
approved OTC new animal drugs to
comply with other applicable
requirements in proposed subpart H (see
proposed § 201.407).
1. Labeling Providing Full Product
Information (Proposed § 201.407(a))
The proposed rule uses the term ‘‘full
prescribing information’’ to identify all
information necessary for the safe and
effective use of approved or
conditionally approved Rx new animal
drugs, and the proposed regulations use
that term for Rx new animal drugs. The
concept of a component of labeling
providing all information necessary for
the safe and effective use of an approved
or conditionally approved OTC new
animal drug is equally important. FDA
proposes that the term used for this
information for approved or
conditionally approved OTC new
animal drugs would be ‘‘full product
information’’ because OTC new animal
drugs are not prescribed.
The proposed rule would establish
content and format requirements for the
component of labeling that provides full
product information for approved or
conditionally approved OTC new
animal drugs (see proposed
§ 201.407(a)).
If a package insert is provided with an
approved or conditionally approved
OTC new animal drug, the proposed
rule would require the package insert to
include full product information (see
proposed § 201.407(a)). If a package
insert is provided with an approved or
conditionally approved OTC new
animal drug, the label would be
required to comply with proposed
§ 201.407(b) or (c), and any secondary
container labeling would be required to
comply with proposed § 201.407(d).
If a package insert is not provided
with an approved or conditionally
approved OTC new animal drug, but a
secondary container is provided, then
the secondary container labeling would
be required to provide full product
information (see proposed § 201.407(a)).
If full product information is provided
on the secondary container labeling, in
accordance with section 201(k) of the
FD&C Act, proposed § 201.407(a) would
allow the secondary container labeling
to exclude any portions of full product
information that would be required to
appear on the label if such information
is easily legible through the secondary
container (see proposed § 201.407(a)).
If no package insert or secondary
container is provided with an approved
or conditionally approved OTC new
animal drug, then the label would be
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required to include full product
information (see proposed § 201.407(a)).
The proposed rule would require the
following information to be presented in
full product information for approved or
conditionally approved OTC new
animal drugs and in the following order.
Unless otherwise indicated, this
information would be the same as that
required by proposed § 201.405(a) for
full prescribing information for
approved or conditionally approved Rx
new animal drugs.
a. Drug product identification. The
proposed rule would require this
section of full product information to
include the proprietary name of the
finished drug product and the
established name of the drug product. If
not included as part of the established
name of the drug product, the route(s)
of administration and dosage form of the
finished drug product would be
required to be included in this section
as well (see proposed § 201.407(a)(1)(i)
through (iv)).
The established name and strength or
concentration of each active ingredient
would also be required. The strength or
concentration of each active ingredient
would be allowed to be excluded from
full product information provided on a
package insert if the package insert
applies to multiple strengths or
concentrations for the same OTC new
animal drug (see proposed
§ 201.407(a)(1)(v)).
If FDA determines that identifying the
pharmacological class of an OTC new
animal drug on labeling would be
helpful in facilitating its safe and
effective use, the proposed rule would
require that the pharmacological class
be included in this section of full
product information (see proposed
§ 201.407(a)(1)(vi)).
b. Conditional approval statement.
For conditionally approved OTC new
animal drugs, the proposed rule would
require this section of full product
information to include a conditional
approval statement, as described in
proposed § 201.405(a)(3) for full
prescribing information for
conditionally approved Rx new animal
drugs (see proposed § 201.407(a)(2)).
c. ‘‘Uses.’’ This section of full product
information would be required to have
the heading ‘‘Uses,’’ followed by the
approved or conditionally approved
indication(s) and target animal(s) in the
following format: ‘‘For [indication(s)] in
[target animal(s)]’’ (see proposed
§ 201.407(a)(3)).
This section of full product
information would be similar to the
‘‘Indications for Use’’ section of full
prescribing information for Rx new
animal drugs, as described in proposed
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§ 201.405(a)(7). For OTC new animal
drugs, the heading ‘‘Uses’’ may be better
understood by the layperson and is
consistent with the requirements for
labeling of OTC human drugs (see
§ 201.66(c)(4)).
If FDA approves or conditionally
approves an OTC new animal drug for
use only under specific conditions, such
as in conjunction with a specific diet,
then the proposed rule would require
that this information be specified in the
‘‘Uses’’ section of full product
information (see proposed
§ 201.407(a)(3)(ii)).
FDA may require a statement in the
‘‘Uses’’ section of full product
information describing the relative
effectiveness of doses within the
approved range of doses (see proposed
§ 201.407(a)(3)(iii)). This requirement
primarily pertains to OTC new animal
drugs that affect the structure or
function of the body of an animal
(section 201(g)(1)(C) of the FD&C Act)
but are not intended for use in the
diagnosis, cure, mitigation, treatment, or
prevention of disease (section
201(g)(1)(B) of the FD&C Act), e.g., drugs
that increase the rate of weight gain or
feed efficiency in food-producing
animals. For these new animal drugs, all
doses within the range presented on the
approved labeling must be effective for
their intended use(s) (see 21 CFR
514.4(b)(2)(i)). For new animal drugs
intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of
disease, the lowest dose of the dose
range must be effective for the intended
use(s). However, the doses within the
approved range do not need to be more
effective than any other doses within
the same range. For OTC new animal
drugs approved for structure or function
indications, if the highest approved
dose(s) is not more effective compared
to the next lower approved dose(s), the
proposed rule would be able to require
a statement in the ‘‘Uses’’ section to
inform the user that a higher dose(s) is
not more effective than the next lower
dose(s).
For safety and/or effectiveness
reasons, we may require a statement(s)
in the ‘‘Uses’’ section of full product
information identifying animals for
which the OTC new animal drug has not
been approved or conditionally
approved (see proposed
§ 201.407(a)(3)(iv)).
d. Extralabel use statement. The
proposed rule would require this
section of full product information to
include an extralabel use statement (see
proposed § 201.407(a)(4)). In accordance
with part 530, extralabel use of
approved new animal drugs is not
permitted except by or on the order of
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a licensed veterinarian and under the
conditions described in that chapter.
The required statement would be: ‘‘It is
a violation of Federal law to use this
drug product other than as directed in
the labeling or as directed by your
veterinarian.’’ It is important for the
layperson to know when it is a violation
of Federal law to use drugs in animals
in an extralabel manner.
e. Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use, in
accordance with § 530.41, the proposed
rule would require this section of full
product information to include an
extralabel use prohibition statement, as
described in proposed § 201.405(a)(5)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(a)(5)). Few OTC new animal
drugs are prohibited from extralabel use
under § 530.41. However, for the rare
situation in which an approved OTC
new animal drug is prohibited from
extralabel use under § 530.41, this
statement would be included in
addition to the appropriate extralabel
use statement that would be required by
proposed § 201.407(a)(4).
f. ‘‘Description.’’ The proposed rule
would require this section of full
product information to have the heading
‘‘Description,’’ followed by a
description of the new animal drug. The
description would include the
proprietary name of the finished drug
product and established name of the
drug product, and the route(s) of
administration and dosage form if not
included as part of the established
name. The description would also
include identifying characteristics of the
dosage form, such as color, shape,
coating, scoring, and imprinting. All
approved and available strengths or
concentrations of the new animal drug
to which full product information
applies would need to be identified in
this section of full product information.
If the drug product was sterile, this fact
would also be identified in this section
of full product information (see
proposed § 201.407(a)(6)).
When inactive ingredients are
provided on the labeling, the proposed
rule would require they be listed in the
‘‘Description’’ section in decreasing
order of predominance, by weight or
concentration (see proposed
§ 201.407(a)(6)(viii)). We encourage
sponsors to list all inactive ingredients
on labeling to better inform users about
the product.
g. ‘‘Warnings.’’ The proposed rule
would require this section of full
product information for all approved or
conditionally approved OTC new
animal drugs, and it would have the
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heading ‘‘Warnings’’ (see proposed
§ 201.407(a)(7)). This section of full
product information would be similar to
the ‘‘Warnings and Precautions’’ section
proposed for full prescribing
information for Rx new animal drugs, as
described in proposed § 201.405(a)(10).
However, ‘‘precautions’’ would be
excluded from this section of full
product information and instead be
provided in the ‘‘Additional
Recommendations’’ section of full
product information, as described in
proposed § 201.407(a)(8). A more
complete explanation of the basis for
this proposal is provided in the
discussion of the ‘‘Animal Safety
Warnings’’ subsection for OTC new
animal drugs in proposed
§ 201.407(a)(7)(iii).
i. ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods.’’ All
OTC new animal drugs approved or
conditionally approved for use in foodproducing animals, would be required
to have as the first subsection of the
‘‘Warnings’’ section of full product
information a subsection with the
heading ‘‘Withdrawal Periods and
Residue Warnings’’ or ‘‘Withdrawal
Periods.’’ This subsection would
provide human food safety warnings,
including milk discard times,
withdrawal periods, and residue
warning statements, as applicable to the
new animal drug (see proposed
§ 201.407(a)(7)(i)). This subsection of
full product information would be the
same as described in proposed
§ 201.405(a)(10)(i) for full prescribing
information for Rx new animal drugs.
ii. ‘‘User Safety Warnings.’’ The
proposed rule would require this
subsection of the ‘‘Warnings’’ section of
full product information to have the
heading ‘‘User Safety Warnings,’’
followed by the user safety warnings
(see proposed § 201.407(a)(7)(ii)). This
subsection of full product information
would be the same as described in
proposed § 201.405(a)(10)(ii) for full
prescribing information for Rx new
animal drugs.
iii. ‘‘Animal Safety Warnings.’’ For
OTC new animal drugs with
contraindications, target animal safety
warnings that identify any serious
adverse reaction or potential hazard to
the target animal(s) associated with the
use of the new animal drug, adverse
reactions, or post-approval adverse drug
experiences, the proposed rule would
require this subsection of the
‘‘Warnings’’ section of full product
information to have the heading
‘‘Animal Safety Warnings,’’ followed by
the contraindications, target animal
safety warnings, adverse reactions, and
post-approval adverse drug experiences
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(see proposed § 201.407(a)(7)(iii)). This
proposed subsection of full product
information would differ in some ways
from the ‘‘Animal Safety Warnings and
Precautions’’ subsection of full
prescribing information proposed for Rx
new animal drugs, as described in
proposed § 201.405(a)(10)(iii), and these
differences are the basis for the different
proposed titles of these sections, i.e.,
‘‘Warnings’’ for OTC new animal drugs
versus ‘‘Warnings and Precautions’’ for
Rx new animal drugs.
The definition of ‘‘precautions’’ in
proposed § 201.403 is ‘‘any special care
to be exercised for safe and effective use
of the new animal drug. This may
include recommended screening,
monitoring, or diagnostic tests.’’
Precautions related to Rx new animal
drugs may include screening, special
care and monitoring, or diagnostic tests
intended to be performed by a
veterinarian. Furthermore, precautions
related to Rx new animal drugs are often
related to, and difficult to distinguish
from, target animal safety warnings. On
the other hand, OTC new animal drugs
do not require professional veterinary
expertise to properly administer the
drug, provide adequate post-treatment
care, or monitor effects after use of the
drug. For OTC new animal drugs,
precautions provide additional
recommendations to the layperson and
are distinguishable from target animal
safety warnings. For example, this may
include information on when to
administer the drug relative to feeding,
or a recommendation to have a sound
mastitis monitoring program before
using the drug, etc. This advice is
distinguishable from warnings for OTC
new animal drugs. Therefore, for better
clarity to the layperson, we propose that
precautions for OTC new animal drugs
not be included in the ‘‘Animal Safety
Warnings’’ section of full product
information and instead would be
included in a separate section called
‘‘Additional Recommendations,’’ as
described in proposed § 201.407(a)(8).
In addition, the ‘‘Animal Safety
Warnings’’ subsection of full product
information for OTC new animal drugs
would differ from the ‘‘Animal Safety
Warnings and Precautions’’ subsection
of full prescribing information for Rx
new animal drugs in terms of
presentation of warning information.
For OTC new animal drugs, all potential
risks of the drug to the target animal
would be included: contraindications,
target animal safety warnings, adverse
reactions, and post-approval adverse
drug experiences as determined by FDA.
For Rx new animal drugs, this
information would be provided in
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different sections of full prescribing
information.
For OTC new animal drugs, including
all potential risks to the target animal in
one subsection of full product
information might be clearer for the
layperson and increase the likelihood
that all of the information would be
read. Furthermore, identifying the risks
to the target animal on labeling as
‘‘contraindications,’’ ‘‘target animal
safety warnings,’’ ‘‘adverse reactions,’’
or ‘‘post-approval adverse drug
experience’’ may be confusing to a
layperson because they may not know
the differences between the terms. The
subsection heading ‘‘Animal Safety
Warnings’’ would be understood by the
layperson as meaning risks to the target
animal. Therefore, the proposed rule
would require that all risks to the target
animal for OTC new animal drugs be
simply identified as ‘‘Animal Safety
Warnings’’ and placed in this subsection
of full product information. All risk
information listed under ‘‘Animal Safety
Warnings’’ would be required to be
listed in decreasing order of severity to
emphasize the most critical risks to the
target animal (see proposed
§ 201.407(a)(7)(iii)).
iv. ‘‘Environmental Warnings.’’ For
new animal drugs having environmental
warnings, the proposed rule would
require this subsection of the
‘‘Warnings’’ section of full product
information to have the heading
‘‘Environmental Warnings,’’ followed by
the environmental warnings (see
proposed § 201.407(a)(7)(iv)). This
subsection of full product information
would be the same as described in
proposed § 201.405(a)(10)(iv) for full
prescribing information for Rx new
animal drugs.
v. ‘‘Other Warnings.’’ For OTC new
animal drugs having warnings not more
appropriately placed in other
‘‘Warnings’’ subsections, the proposed
rule would require the last subsection of
the ‘‘Warnings’’ section of full product
information to have the heading ‘‘Other
Warnings,’’ followed by those warnings
(see proposed § 201.407(a)(7)(v)). This
subsection of full product information
would be the same as described in
proposed § 201.405(a)(10)(v) for full
prescribing information for Rx new
animal drugs.
h. ‘‘Additional Recommendations.’’
For OTC new animal drugs having
precautions, the proposed rule would
require this section of full product
information to have the heading
‘‘Additional Recommendations,’’
followed by all precautions (see
proposed § 201.407(a)(8)). As described
in its proposed definition, precautions
include any special care to be exercised
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for safe and effective use of the new
animal drug. As discussed with respect
to proposed § 201.407(a)(7)(iii),
regarding ‘‘Animal Safety Warnings,’’
precautions are distinguishable from
target animal safety warnings for OTC
new animal drugs. However, because
the term ‘‘precautions’’ as intended by
these proposed regulations may not be
known or understood by the layperson,
the title ‘‘Additional
Recommendations’’ is proposed.
i. ‘‘Other Effects You May Notice.’’
For OTC new animal drugs that have
effects on the target animal(s) that are
not considered contraindications, target
animal safety warnings, adverse
reactions, or post-approval adverse drug
experiences, and FDA determines these
effects are required to be described on
labeling, the proposed rule would
require this section of full product
information to have the heading ‘‘Other
Effects You May Notice,’’ followed by a
description of the effects (see proposed
§ 201.407(a)(9)). We consider this
information important for owners of
animals, and this information is
currently provided on the labeling of
some OTC new animal drugs.
For example, some OTC new animal
drugs approved for increased rate of
weight gain and/or feed efficiency in
feedlot beef cattle have effects on the
leanness or tenderness of the carcass of
those animals. Similarly, OTC new
animal drugs that increase milk
production in dairy cows or the
efficiency by which they produce milk
may alter the fat percent content of the
milk. These effects, which are currently
described on the approved labeling for
these products, are not considered
negative health effects on the target
animal nor are they of human food
safety concern. However, these effects
could be mistaken for symptoms of an
underlying health problem in the target
animal, such as poor nutritional status.
For this reason, information of this type
may be considered material under
section 201(n) of the FD&C Act such
that it would be required to be disclosed
in the labeling for these products on the
basis that such disclosures may
preclude unnecessary concern and
inappropriate medical treatment.
Similarly, some topically applied OTC
new animal drugs for companion
animals might permanently (but
harmlessly) alter the color of the fur at
the application site. These types of
potential effects that are not safety
concerns, but rather provide important
information to the layperson, would be
included in this section of full product
information.
j. ‘‘Directions.’’ The proposed rule
would require this section of full
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product information to have the heading
‘‘Directions,’’ followed by the directions
for use of the OTC new animal drug for
each indication and target animal (see
proposed § 201.407(a)(10)). The
corresponding section of full prescribing
information for Rx new animal drugs
would be called ‘‘Dosage and
Administration,’’ as described in
proposed § 201.405(a)(9). However, for
OTC new animal drugs, the term
‘‘Directions’’ may be better understood
by the layperson. In addition, the term
‘‘Directions’’ is also used in labeling of
OTC human drugs (see § 201.66(c)(6)).
The ‘‘Directions’’ section of full
product information is intentionally
proposed for placement after the
‘‘Warnings’’ section. This is in contrast
to the ‘‘Dosage and Administration’’
section in full prescribing information
for Rx new animal drugs, which, except
for ‘‘Boxed Warnings,’’ would be placed
before ‘‘Contraindications,’’ ‘‘Warnings
and Precautions,’’ ‘‘Adverse Reactions,’’
and other information about the effects
of the drug. The intent in presenting
‘‘Directions’’ after the ‘‘Warnings’’
section in full product information for
OTC new animal drugs is to increase the
likelihood that the layperson will read
the ‘‘Warnings’’ section before using the
drug. This placement approach is
similar to that used in labeling of OTC
human drugs (see § 201.66(c)(6)).
The ‘‘Directions’’ section of full
product information would be required
to include information necessary for
treatment of the animal with the OTC
new animal drug in accordance with
FDA approval or conditional approval,
including route(s) of administration;
specific site(s) of administration, if
applicable; dose or dose range, intervals
between doses, if applicable; and
duration of treatment. For some
injectable products, FDA may require a
statement of maximum volume per
injection site to facilitate the drug’s safe
and effective use, and the proposed rule
would require this information to be
included in this section of full product
information. Other required dosage and
administration information would be
included in this section of full product
information. See proposed
§ 201.407(a)(10).
k. ‘‘Net Contents.’’ The proposed rule
would require this section of full
product information, when presented on
the label or the secondary container
labeling, to have the heading ‘‘Net
Contents,’’ followed by the contents of
the immediate container, in accordance
with § 201.62 (21 CFR 201.62), or the
secondary container, respectively. The
proposed rule would exclude a ‘‘Net
Contents’’ section from package inserts
(see proposed § 201.407(a)(11)).
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l. ‘‘How Supplied.’’ The proposed rule
would require this section of full
product information to have the heading
‘‘How Supplied,’’ followed by
information on available strengths,
concentrations, and container sizes to
which the labeling applies (see
proposed § 201.407(a)(12)). This section
of full product information would be the
same as described in proposed
§ 201.405(a)(19) for full prescribing
information for Rx new animal drugs.
m. ‘‘Storage, Handling, and
Disposal.’’ The proposed rule would
require this section of full product
information to have the heading
‘‘Storage, Handling, and Disposal,’’
followed by drug storage information, as
well as any required handling and drug
disposal information (see proposed
§ 201.407(a)(13)). This section of full
product information would be the same
as described in proposed
§ 201.405(a)(20) for full prescribing
information for Rx new animal drugs.
n. ‘‘Questions/Comments?’’ The
proposed rule would require this
section of full product information to
have the heading ‘‘Questions/
Comments?,’’ followed by the sponsor’s
contact information for consumers to
facilitate requesting additional
information or to report suspected
adverse drug experiences. FDA’s contact
information for voluntary reporting of
adverse drug experiences for animal
drugs would also be required (see
proposed § 201.407(a)(14)). The
‘‘Questions/Comments?’’ section of full
product information would be similar to
the ‘‘Contact Information’’ section in
proposed § 201.405(a)(12) for full
prescribing information for Rx new
animal drugs.
The ‘‘Questions/Comments?’’ heading
might be clearer than ‘‘Contact
Information’’ to the layperson using
OTC new animal drugs. Furthermore,
the heading ‘‘Questions?’’ or ‘‘Questions
or comments?’’ is used for OTC human
drug labeling (see § 201.66(c)(9)). Also,
the phrase ‘‘To report side effects,
contact . . .’’ is proposed for full
product information for OTC new
animal drugs rather than ‘‘To report
suspected adverse drug experiences,
contact . . .,’’ which is the phrase
proposed for full prescribing
information for Rx new animal drugs.
The term ‘‘side effects’’ may be better
understood by the layperson than the
term ‘‘suspected adverse drug
experiences.’’ Also, the term ‘‘side
effects’’ may be used in labeling of OTC
human drugs (see § 201.66(c)(5)(vii) (21
CFR 201.66(c)(5)(vii)).
The sponsor’s contact information
would be the name of the manufacturer,
packer, or distributor, whichever is
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identified in the ‘‘Name and place of
business’’ section of full product
information (see proposed
§ 201.407(a)(16)). If more than one
business is identified in the ‘‘Name and
place of business’’ section of full
product information, the drug sponsor
would select the most appropriate of
these businesses to use in the
‘‘Questions/Comments?’’ section to
provide additional information about
the OTC new animal drug and to contact
regarding suspected adverse drug
experiences.
The statements in this section of full
product information would be required
to be structured as follows: ‘‘Contact
[insert name of business] at [insert
business telephone number] or [insert
business web address]. To report side
effects, contact [insert name of business]
at [insert business telephone number].
For additional information about
reporting side effects for animal drugs,
contact FDA at [insert current FDA
telephone number for voluntary
reporting of adverse drug experiences]
or [insert current FDA web address for
voluntary reporting of adverse drug
experiences].’’ Sponsors can search
FDA’s website or contact FDA by
telephone to find the current FDA
telephone number or web address for
voluntary reporting of adverse drug
experiences for animal drugs.
o. NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the proposed rule would require
this section of full product information
to include an ‘‘NADA approval
statement’’ or ‘‘ANADA approval
statement,’’ respectively (see proposed
§ 201.407(a)(15)). This section of full
product information would be the same
as described in proposed
§ 201.405(a)(21) for full prescribing
information for Rx new animal drugs.
p. Name and place of business. The
proposed rule would require this
section of full product information to
identify the name and place of business
of the manufacturer, packer, or
distributor (see proposed
§ 201.407(a)(16)). This section of full
product information would be the same
as described in proposed
§ 201.405(a)(22) for full prescribing
information for Rx new animal drugs.
q. ‘‘Lot Number and Expiration Date.’’
The proposed rule would require this
section of full product information
when provided on the secondary
container labeling or the label. Package
inserts are excluded from this
requirement because they might apply
to multiple lots of secondary or
immediate containers of the OTC new
animal drug. When full product
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information is provided on the
secondary container labeling or the
label, this section would be required to
have the heading ‘‘Lot Number and
Expiration Date,’’ followed by the
identifying lot or control number of the
OTC new animal drug within the
secondary container or immediate
container (see proposed
§ 201.407(a)(17)). A lot or control
number would help us more easily to
identify and trace back a specific lot of
a product should a problem be reported
to FDA. The proposed rule would also
require this section to include the
expiration date of the OTC new animal
drug within the secondary container or
immediate container, in accordance
with § 201.17. An expiration date better
ensures that the new animal drug would
not be used after it expires.
Alternatively, the proposed rule
would allow for this section of full
product information to refer to the
location on the secondary container
labeling, secondary container, label, or
immediate container where the lot or
control number and expiration date are
printed (see proposed § 201.407(a)(17)).
As an example, if the lot number and
expiration date are printed on the
bottom flap of a secondary container,
then the secondary container labeling
may state in this section, ‘‘See carton
bottom flap for lot number and
expiration date.’’ However, if full
product information is provided on the
secondary container labeling, in
accordance with § 201.17, the proposed
rule would allow an expiration date to
be excluded from the secondary
container labeling or secondary
container if the expiration date provided
on the label or immediate container is
easily legible through the secondary
container.
r. ‘‘Revision Date.’’ The proposed rule
would require this section of full
product information to have the heading
‘‘Revision Date,’’ followed by the date of
the most recent revision of the
component of labeling that provides full
product information, listing the month
followed by the year (see proposed
§ 201.407(a)(18)). This information is
important to ensure that the most
current approved version of the labeling
is being used.
2. OTC New Animal Drug Label Not
Providing Full Product Information
(OTC Label) (Proposed § 201.407(b))
The proposed rule would establish
content and format requirements for the
information presented on the label for
approved or conditionally approved
OTC new animal drugs (OTC label)
where the label does not provide full
product information (see proposed
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§ 201.407(b)). As described previously
in section V.E.1 regarding labeling
providing full product information, the
label for an OTC new animal drug
would include full product information
only if there is no package insert or
secondary container labeling.
Proposed § 201.407(b) would apply to
OTC labels that are of adequate size to
contain the proposed required
information per that paragraph, whereas
proposed § 201.407(c) would apply to
small labels for OTC new animal drugs
that are not of adequate size to contain
all the proposed required information in
proposed § 201.407(b).
OTC new animal drugs labels to
which § 201.407(b) would apply may
consist of a single panel, a front panel
and one side or back panel, or a front
panel and multiple side and/or back
panels, and the proposed rule would
provide for such label designs (see
proposed § 201.407(b)). For OTC labels
with a front panel and one side or back
panel, the proposed rule would require
certain information for the front panel
(see proposed § 201.407(b)(1)), and the
side or back panel (see proposed
§ 201.407(b)(2)). For OTC labels
consisting of a single panel, the
proposed rule would require the
information identified in proposed
§ 201.407(b)(1) followed by the
information identified in proposed
§ 201.407(b)(2), in order, on the single
panel. For OTC labels with a front panel
and multiple side and/or back panels,
the information identified in proposed
§ 201.407(b)(1) followed by the
information identified in proposed
§ 201.407(b)(2) would be required in
order, starting on the front panel,
continuing on the panel immediately to
the right of the front panel, and
continuing to fill the panels to the right
until all of the information in proposed
§ 201.407(b)(1) and (2) was presented. In
all instances, the information in
proposed § 201.407(b)(2)(iii) and (iv),
concerning active ingredients and
inactive ingredients, would need to
appear on the same panel.
a. Front panel. The proposed rule
would require the following information
to be presented on the front panel of the
OTC label for an approved or
conditionally approved OTC new
animal drug and in the following order
(see proposed § 201.407(b)(1)). Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information for approved or
conditionally approved Rx new animal
drugs or proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs.
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i. Drug product identification. The
proposed rule would require this
section of the OTC label to include drug
product identification (see
§ 201.407(b)(1)(i)). This information may
help the user to identify the product
quickly and correctly and distinguish it
from other, similar products. The
information included in this section of
the OTC label would include the same
information as that in the drug product
identification section of full product
information, as described in proposed
§ 201.407(a)(1), in addition to a
statement that the drug product is
sterile, if applicable. Full product
information would require a drug
product identification section and
‘‘Description’’ section. Full product
information for sterile OTC new animal
drugs would be required to identify in
the ‘‘Description’’ section that the drug
is sterile. However, due to space
limitations, no ‘‘Description’’ section is
proposed for the OTC label. Instead, the
drug product identification section of
the OTC label for sterile OTC new
animal drugs would be required to state
that the drug product is sterile. See
proposed § 201.407(b)(1)(i).
ii. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the OTC label to include
a conditional approval statement, as
described in proposed § 201.405(a)(3))
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(b)(1)(ii)).
iii. ‘‘Uses.’’ The proposed rule would
require this section of the OTC label to
have the heading ‘‘Uses,’’ followed by
the ‘‘Uses’’ section, as described in
proposed § 201.407(a)(3) for full product
information. If there is insufficient
space on the OTC label for the complete
‘‘Uses’’ section as described in proposed
§ 201.407(a)(3), then the proposed rule
would require the sponsor to include in
this section of the OTC label the
statement required in proposed
§ 201.407(a)(3)(i), i.e., ‘‘For
[indication(s)] in [target animal(s)]’’. If
there is insufficient space on the OTC
label for the statement in proposed
§ 201.407(a)(3)(i), then an abbreviated
version of the statement would be
required: ‘‘For [abbreviated
indication(s)] in [target animal(s)].’’ In
either situation where there is
insufficient space on the OTC label for
the complete ‘‘Uses’’ section as
specified in proposed § 201.407(a)(3),
the required statement would be
followed by one of the following
statements: ‘‘See package insert for
complete ‘Uses’’’ if full product
information is provided on a package
insert; or ‘‘See package labeling for
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complete ‘Uses’’’ if full product
information is provided on the
secondary container labeling. See
proposed § 201.407(b)(1)(iii). The
complete ‘‘Uses’’ section as described in
proposed § 201.407(a)(3) may exceed the
available space on the OTC label if, for
example, it includes specific conditions
of use (proposed § 201.407(a)(3)(ii)), a
statement describing the relative
effectiveness of doses within the
approved range of doses (proposed
§ 201.407(a)(3)(iii)), animals for which
the new animal drug is not approved or
conditionally approved (proposed
§ 201.407(a)(3)(iv), and/or the
indication(s) is lengthy and/or complex.
iv. Extralabel use statement. The
proposed rule would require this
section of the OTC label to include the
extralabel use statement, as described in
proposed § 201.407(a)(4) for full product
information (see proposed
§ 201.407(b)(1)(iv)).
v. Extralabel use prohibition
statement. For approved OTC new
animal drugs prohibited from extralabel
use, in accordance with § 530.41, the
proposed rule would require this
section of the OTC label to include the
extralabel use prohibition statement, as
described in proposed § 201.405(a)(5)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(b)(1)(v)).
vi. ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods.’’
For new animal drugs approved or
conditionally approved for use in foodproducing animals, the proposed rule
would require this section of the OTC
label to have the heading ‘‘Withdrawal
Periods and Residue Warnings’’ or
‘‘Withdrawal Periods,’’ followed by all
human food safety warnings, including
milk discard times, withdrawal periods,
and residue warning statements, as
described in proposed
§ 201.405(a)(10)(i) for full prescribing
information for Rx new animal drugs. If
there is insufficient space on the front
panel of the OTC labels with only a
front panel and one side or back panel,
the proposed rule would require this
section to be provided on the side or
back panel of the OTC label
immediately following the complete
product information statement specified
in proposed § 201.407(b)(2)(i). See
proposed § 201.407(b)(1)(vi).
vii. ‘‘Net Contents.’’ The proposed
rule would require this section of the
OTC label to have the heading ‘‘Net
Contents,’’ followed by the contents of
the immediate container, in accordance
with § 201.62 (see proposed
§ 201.407(b)(1)(vii)).
viii. NADA/ANADA approval
statement. For approved new animal
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drugs or approved generic new animal
drugs, the proposed rule would require
this section of the OTC label to include
the NADA or ANADA approval
statement, as described in proposed
§ 201.405(a)(21) for full prescribing
information for Rx new animal drugs
(see proposed § 201.407(b)(1)(viii)).
b. Side or back panel. The proposed
rule would require the following
information to be presented on the side
or back panel of the OTC label for an
approved or conditionally approved
OTC new animal drug in the following
order (see proposed § 201.407(b)(2)).
Unless otherwise indicated, this
information would be the same as that
required by proposed § 201.405(a) for
full prescribing information for
approved or conditionally approved Rx
new animal drugs or proposed
§ 201.407(a) for full product information
for approved or conditionally approved
OTC new animal drugs.
i. Complete product information
statement. The proposed rule would
require this section of the OTC label to
include one of two statements (see
proposed § 201.407(b)(2)(i)). If full
product information is provided on the
package insert, the following statement
would be used: ‘‘Before using this drug,
read package insert for complete
product information.’’ If full product
information is provided on the
secondary container labeling, the
following statement would be used:
‘‘Before using this drug, read package
labeling for complete product
information.’’ Because full product
information would not be provided on
the OTC label, the purpose of the
statements would be to remind the user
to read full product information before
using the OTC new animal drug.
ii. ‘‘Directions.’’ The proposed rule
would require this section of the OTC
label to have the heading ‘‘Directions,’’
followed by the ‘‘Directions’’ section as
described in proposed § 201.407(a)(10)
for full product information. If there is
insufficient space on the OTC label for
the complete requirements as specified
in § 201.407(a)(10), or if it is necessary
for additional information provided in
full product information that is not
provided on the OTC label to be read
before administering the drug (e.g.,
complete warnings and/or additional
recommendations), then FDA may
exclude this section from the OTC label
(see proposed § 201.407(b)(2)(ii)). For
example, if an OTC new animal drug is
approved for multiple indications and/
or target animals, there may be different
target animal safety warnings or
precautions associated with each
indication and/or target animal. This
information would be provided in full
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product information for the OTC new
animal drug (in the ‘‘Animal Safety
Warnings’’ subsection and ‘‘Additional
Recommendations’’ section,
respectively), but there may be
insufficient space for it on the OTC
label. Excluding the ‘‘Directions’’
section from the OTC label in this
situation helps to ensure that the user
would read full product information,
which would include the ‘‘Directions’’
section as well as the ‘‘Animal Safety
Warnings’’ subsection and ‘‘Additional
Recommendations’’ section, before
treating the animal. The user would also
be reminded to read full product
information before using the drug via
the complete product information
statement that would be required in the
previous section of the OTC label by
proposed § 201.407(b)(2)(i).
iii. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the OTC label to
have the heading ‘‘Active Ingredient’’ or
‘‘Active Ingredients,’’ followed by the
established name and strength or
concentration of each active ingredient
(see proposed § 201.407(b)(2)(iii)).
iv. ‘‘Inactive Ingredients.’’ When
inactive ingredients are provided on the
OTC label, the proposed rule would
require they be listed in the ‘‘Inactive
Ingredients’’ section in decreasing order
of predominance, by weight or
concentration, as described in proposed
§ 201.405(a)(6)(viii) for full prescribing
information for Rx new animal drugs
(see proposed § 201.407(b)(2)(iv)).
v. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the OTC label to have the
heading ‘‘Storage, Handling, and
Disposal,’’ followed by drug storage,
handling, and disposal information, as
described in proposed § 201.405(a)(20)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(b)(2)(v)).
vi. Name and place of business. The
proposed rule would require this
section of the OTC label to identify the
name and place of business of the
manufacturer, packer, or distributor, as
required in section 502(b) of the FD&C
Act (see proposed § 201.407(b)(2)(vi)).
vii. ‘‘Lot Number and Expiration
Date’’ or ‘‘Lot Number’’. The proposed
rule would require this section of the
OTC label to have the heading ‘‘Lot
Number and Expiration Date’’ or ‘‘Lot
Number,’’ followed by the identifying
lot or control number of the OTC new
animal drug within the immediate
container (see proposed
§ 201.407(b)(2)(vii)). A lot or control
number would allow us more easily to
identify and trace back a specific lot of
a product should a problem be reported
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to FDA. We would also require this
section of the OTC label to include the
expiration date of the OTC new animal
drug within the immediate container, in
accordance with § 201.17. An expiration
date on the OTC label better ensures
that the new animal drug would not be
used after it expires. Alternatively, the
proposed rule would allow for this
section to refer to the location on the
OTC label or immediate container
where the lot or control number and
expiration date are printed (see
proposed § 201.407(b)(2)(vii)). As an
example, if the lot number and
expiration date are printed at the top of
the immediate container, then the OTC
label may state in this section, ‘‘See top
of container for lot number and
expiration date.’’ If the immediate
container provides a single dose of the
OTC new animal drug and is packaged
individually in a secondary container
that provides an expiration date on the
secondary container labeling or
secondary container, the proposed rule
would not require an expiration date on
the OTC label or immediate container,
in accordance with § 201.17. Under
such provision, this section of the OTC
label would be required to be entitled
‘‘Lot Number.’’
viii. ‘‘Revision Date.’’ The proposed
rule would require the last section of the
OTC label to have the heading
‘‘Revision Date,’’ followed by the date of
the most recent revision of the OTC
label, listing the month followed by the
year (see proposed § 201.407(b)(2)(viii)).
3. OTC New Animal Drug Small Label
(OTC Small Label) (Proposed
§ 201.407(c))
The proposed rule would establish
content and format requirements for the
small label for OTC new animal drugs
(OTC small label) where the label does
not provide full product information
(see proposed § 201.407(c)).
Some immediate containers, such as
blister packs, pre-filled syringes, and
small vials, are so small that only a
minimal amount of information can be
included on their label. The proposed
rule would establish requirements for
OTC small labels for approved or
conditionally approved OTC new
animal drugs (see proposed
§ 201.407(c)). We recognize that the size
of the label is dependent upon the size
of the immediate container. If an
immediate container lacks sufficient
space to contain a label that
accommodates all of the information
required by proposed § 201.407(a) or (b),
the requirements of proposed
§ 201.407(c) would instead apply. We
would ordinarily make this
determination during the review of the
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new animal drug and its labeling, taking
into consideration the readability and
legibility of the information.
The proposed rule would require the
following information to be presented
on the OTC small label for an approved
or conditionally approved OTC new
animal drug and in the following order
(see proposed § 201.407(c)).
a. Proprietary name of the finished
drug product. The proposed rule would
require this section of the OTC small
label to include the proprietary name of
the finished drug product (see proposed
§ 201.407(c)(1)). This requirement
already exists for small labels for drugs
in general in § 201.10(i)(1), but is
repeated in these proposed regulations
to include all requirements for labeling
of approved or conditionally approved
new animal drugs in proposed subpart
H.
b. Established name of the drug
product. The proposed rule would
require this section of the OTC small
label to include the established name of
the drug product (see proposed
§ 201.407(c)(2)). This requirement
already exists for small labels for drugs
in general in § 201.10(i)(1), but is
repeated in these proposed regulations
to include all requirements for labeling
of approved or conditionally approved
new animal drugs in proposed subpart
H.
c. Active ingredient(s). The proposed
rule would require this section of the
OTC small label to include the
established name and strength or
concentration of each active ingredient
(see proposed § 201.407(c)(3)). This
information should reduce the risk of
miscalculating doses.
d. ‘‘For [target animal(s)] only.’’ The
proposed rule would require this
section of the OTC small label to
include a brief listing of the approved
target animal(s) as follows: ‘‘For [target
animal(s)] only’’ (see proposed
§ 201.407(c)(4)). The brief listing of the
approved target animal(s) is used in
place of full ‘‘Uses’’ information because
OTC small labels lack sufficient space.
This listing would not require as much
space on the OTC small label.
e. Complete product information
statement. The proposed rule would
require this section of the OTC small
label to include one of two statements.
If full product information is provided
on the package insert, the following
statement would be used: ‘‘Read
package insert for complete product
information’’. If full product
information is provided on the
secondary container labeling, the
following statement would be used:
‘‘Read package labeling for complete
product information.’’ See proposed
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§ 201.407(c)(5). Because full product
information would not be provided on
the OTC small label, the purpose of the
statements would be to remind the user
to read full product information before
using the OTC new animal drug.
f. ‘‘Net Contents.’’ The proposed rule
would require this section of the OTC
small label to have the heading ‘‘Net
Contents,’’ followed by the contents of
the immediate container, in accordance
with § 201.62 (see proposed
§ 201.407(c)(6)).
g. Name and place of business. The
proposed rule would require this
section of the OTC small label to
identify the name and place of business
of the manufacturer, packer, or
distributor, as required in section 502(b)
of the FD&C Act (see proposed
§ 201.407(c)(7)).
h. ‘‘Lot, Exp. and Storage’’ or ‘‘Lot and
Storage.’’ The proposed rule would
require this section of the OTC small
label to have the heading ‘‘Lot, Exp. and
Storage’’ or ‘‘Lot and Storage,’’ followed
by the identifying lot or control number
of the OTC new animal drug within the
immediate container. A lot or control
number would allow FDA more easily
to identify and trace back a specific lot
of a product should a problem be
reported to FDA. The proposed rule
would also require this section of the
OTC small label to include the
expiration date of the OTC new animal
drug within the immediate container, in
accordance with § 201.17. An expiration
date on the OTC small label better
ensures that the new animal drug would
not be used after it expires.
The proposed rule would also require
this section of the OTC small label to
include and drug storage information for
the new animal drug (see proposed
§ 201.407(c)(8)). Storage information is
necessary to maintain potency of the
drug before its expiration date.
Requiring this information on the OTC
small label is needed for safe and
effective use of new animal drugs. If the
immediate container provides a single
dose of the OTC new animal drug and
is packaged individually in a secondary
container that provides an expiration
date on the secondary container labeling
or secondary container, the proposed
rule would not require an expiration
date on the immediate container or OTC
small label, in accordance with § 201.17,
in which case this section of the OTC
small label would be required to be
entitled ‘‘Lot and Storage.’’
i. ‘‘Revision Date.’’ The proposed rule
would require this section of the OTC
small label to have the heading
‘‘Revision Date,’’ followed by the date of
the most recent revision of the OTC
small label, listing the month followed
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by the year (see proposed
§ 201.407(c)(9)).
4. Labeling for Secondary Containers for
OTC New Animal Drugs That Include a
Package Insert (OTC Secondary
Container Labeling) (Proposed
§ 201.407(d))
The proposed rule would establish
content and format requirements for the
information on the labeling for
secondary containers of approved or
conditionally approved OTC new
animal drugs that include a package
insert (OTC secondary container
labeling) (see proposed § 201.407(d)). In
this situation, the package insert would
be required by the proposed regulations
to include full product information as in
proposed § 201.407(a)).
In accordance with section 201(k) of
the FD&C Act, the OTC secondary
container labeling could exclude any
information described in proposed
§ 201.407(d) that would be required to
appear on the OTC label or OTC small
label (see proposed § 201.407(b) or (c),
respectively) if such information on the
OTC label or OTC small label was easily
legible through the secondary container.
The OTC secondary container labeling
to which proposed § 201.407(d) would
apply may consist of a front panel and
one side or back panel, or a front panel
and multiple side and/or back panels.
Proposed § 201.407(d) would provide
for such OTC secondary container
labeling designs. For OTC secondary
container labeling with a front panel
and one side or back panel, proposed
§ 201.407(d)(1) would provide required
information for the front panel, and
proposed § 201.407(d)(2) would provide
required information for the side or back
panel. For OTC secondary container
labeling with a front panel and multiple
side and/or back panels, the information
identified in proposed § 201.407(d)(1)
followed by the information identified
in proposed § 201.407(d)(2) would be
required in order, starting on the front
panel, continuing on the panel
immediately to the right of the front
panel, and continuing to fill the panels
to the right until all of the information
in proposed § 201.407(d)(1) and (2) was
presented. In all instances, the
information proposed in
§ 201.407(d)(2)(iv) and (v), concerning
active ingredients and inactive
ingredients, would need to appear on
the same panel.
a. Front panel. The proposed rule
would require the following information
to be presented on the front panel of the
OTC secondary container labeling and
in the following order (see proposed
§ 201.407(d)(1)). Unless otherwise
indicated, this information would be the
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same as that required by proposed
§ 201.405(a) for full prescribing
information for approved or
conditionally approved Rx new animal
drugs or proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs.
i. Drug product identification. The
proposed rule would require this
section of the OTC secondary container
labeling to include drug product
identification (see proposed
§ 201.407(d)(1)(i)). The information
would be the same as that included in
the drug product identification section
for full product information, as
described in proposed § 201.407(a)(1),
and would also identify if the drug
product is sterile. Full product
information would require a drug
product identification section and a
‘‘Description’’ section. Full product
information for sterile OTC new animal
drugs would be required to identify in
the ‘‘Description’’ section that the drug
is sterile. However, due to space
limitations, no ‘‘Description’’ section
would be required on the OTC
secondary container labeling. Instead,
the drug product identification section
of the OTC secondary container labeling
for sterile OTC new animal drugs would
be required to state that the drug is
sterile.
ii. Conditional approval statement.
For conditionally approved OTC new
animal drugs, the proposed rule would
require this section of the OTC
secondary container labeling to include
a conditional approval statement, as
described in proposed § 201.405(a)(3)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(d)(1)(ii)).
iii. ‘‘Uses.’’ The proposed rule would
require this section of the OTC
secondary container labeling to have the
heading ‘‘Uses,’’ followed by the ‘‘Uses’’
section, as described in proposed
§ 201.407(a)(3) for full product
information (see proposed
§ 201.407(d)(1)(iii)).
iv. Extralabel use statement. The
proposed rule would require this
section of the OTC secondary container
labeling to include the extralabel use
statement as described in proposed
§ 201.407(a)(4) for full product
information (see proposed
§ 201.407(d)(1)(iv)).
v. Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use, in
accordance with § 530.41, the proposed
rule would require this section of the
OTC secondary container labeling to
include the extralabel use prohibition
statement, as described in proposed
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§ 201.405(a)(5) for full prescribing
information for Rx new animal drugs
(see proposed § 201.407(d)(1)(v)).
vi. ‘‘Net Contents.’’ The proposed rule
would require this section of the OTC
secondary container labeling to have the
heading ‘‘Net Contents,’’ followed by
the contents of the secondary container
(see proposed § 201.407(d)(1)(vi)).
vii. NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the proposed rule would require
this section of the OTC secondary
container labeling to include the NADA
or ANADA approval statement, as
described in proposed § 201.405(a)(21)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(d)(1)(vii)).
b. Side or back panel. The proposed
rule would require the following
information to be presented on the side
or back panel of the OTC secondary
container labeling and in the following
order (see proposed § 201.407(d)(2)).
Unless otherwise indicated, this
information would be the same as that
required by proposed § 201.405(a) for
full prescribing information for
approved or conditionally approved Rx
new animal drugs or proposed
§ 201.407(a) for full product information
for approved or conditionally OTC new
animal drugs.
i. Complete product information
statement. The proposed rule would
require this section of the OTC
secondary container labeling to include
the statement, ‘‘Before using this drug,
read package insert for complete
product information’’ (see proposed
§ 201.407(d)(2)(i)). Because full product
information would not be provided on
the OTC secondary container labeling,
the purpose of the Complete product
information statement would be to
remind the user to read full product
information before using the OTC new
animal drug.
ii. ‘‘Directions.’’ The proposed rule
would require this section of the OTC
secondary container labeling to have the
heading ‘‘Directions,’’ followed by the
‘‘Directions’’ section, as described in
proposed § 201.407(a)(10) for full
product information (see proposed
§ 201.407(d)(2)(ii)).
iii. ‘‘Warnings.’’ The proposed rule
would require this section of the OTC
secondary container labeling to have the
heading ‘‘Warnings,’’ followed by the
‘‘Warnings’’ section, as described in
proposed § 201.407(a)(7) for full product
information (see proposed
§ 201.407(d)(2)(iii)).
iv. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the OTC
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secondary container labeling to have the
heading ‘‘Active Ingredient’’ or ‘‘Active
Ingredients,’’ followed by the
established name and strength or
concentration of each active ingredient,
as described in proposed
§ 201.407(b)(2)(iii) for the OTC label (see
proposed § 201.407(d)(2)(iv)).
v. ‘‘Inactive Ingredients.’’ When
inactive ingredients are provided on the
OTC secondary container labeling, the
proposed rule would require they be
listed in the ‘‘Inactive Ingredients’’
section by their established name in
decreasing order of predominance, by
weight or concentration, as described in
proposed § 201.405(a)(6)(viii) (see
proposed § 201.407(d)(2)(v)).
vi. ‘‘Storage, Handling, and
Disposal.’’ The proposed rule would
require this section of the OTC
secondary container labeling to have the
heading ‘‘Storage, Handling, and
Disposal,’’ followed by drug storage,
handling, and disposal information, as
described in proposed § 201.405(a)(20)
for full prescribing information for Rx
animal drugs (see proposed
§ 201.407(d)(2)(vi)).
vii. Name and place of business. The
proposed rule would require this
section of the OTC secondary container
labeling to identify the manufacturer,
packer, or distributor, as described in
proposed § 201.405(a)(22) for full
prescribing information for Rx animal
drugs (see proposed
§ 201.407(d)(2)(vii)).
viii. ‘‘Lot Number and Expiration
Date.’’ The proposed rule would require
this section of the OTC secondary
container labeling to have the heading
‘‘Lot Number and Expiration Date,’’
followed by the identifying lot or
control number of the OTC new animal
drug within the secondary container.
The proposed rule would also require
this section of the OTC secondary
container labeling to include the
expiration date of the OTC new animal
drug within the secondary container, in
accordance with § 201.17. Alternatively,
the proposed rule would allow for this
section to refer to the location on the
OTC secondary container labeling or
secondary container where the lot or
control number and expiration date are
printed (see proposed
§ 201.407(d)(2)(viii)). As an example, if
the lot number and expiration date are
printed on the bottom flap of a
secondary container, then the labeling
may state in this section, ‘‘See carton
bottom flap for lot number and
expiration date.’’ However, in
accordance with § 201.17, the proposed
rule would allow an expiration date to
be excluded from the OTC secondary
container labeling or secondary
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container if the expiration date provided
on the OTC label, OTC small label, or
immediate container is easily legible
through the secondary container.
ix. ‘‘Revision Date.’’ The proposed
rule would require this section of the
OTC secondary container labeling to
have the heading ‘‘Revision Date,’’
followed by the date of the most recent
revision of the OTC secondary container
labeling, listing the month followed by
the year (see proposed
§ 201.407(d)(2)(ix)).
5. Shipping Labeling for OTC New
Animal Drugs (OTC Shipping Labeling)
(Proposed § 201.407(e)
The proposed rule would establish
content and format requirements for the
information on the shipping labeling for
approved or conditionally approved
OTC new animal drugs (OTC shipping
labeling). As defined in proposed
§ 201.403, shipping labeling is
associated with the outermost carton
containing immediate containers,
secondary containers, and/or multiple
unit (multi-unit) cartons of a new
animal drug and intended for shipment,
but not display, of the product. The
proposed rule would require the OTC
shipping labeling to include, among
additional information, drug product
identity, the manufacturer, packer, or
distributor, and drug storage and
handling conditions. See proposed
§ 201.407(e).
The proposed rule would require the
following information to be presented
on the OTC shipping labeling and in the
following order (see proposed
§ 201.407(e)). Unless otherwise
indicated, this information would be the
same as that required by proposed
§ 201.405(a) for full prescribing
information for approved or
conditionally approved Rx new animal
drugs or proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs.
a. Proprietary name of the finished
drug product. The proposed rule would
require this section of the OTC shipping
labeling to include the proprietary name
of the finished drug product (see
proposed § 201.407(e)(1)).
b. Established name of the drug
product. The proposed rule would
require this section of the OTC shipping
labeling to include the established name
of the drug product (see proposed
§ 201.407(e)(2)).
c. Established name and strength or
concentration of each active ingredient.
The proposed rule would require this
section of the OTC shipping labeling
provide the established name and
strength or concentration of each active
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ingredient (see proposed
§ 201.407(e)(3)).
d. Conditional approval statement.
For conditionally approved OTC new
animal drugs, the proposed rule would
require this section of the OTC shipping
labeling to include a conditional
approval statement, as described in
proposed § 201.405(a)(3) for full
prescribing information for Rx new
animal drugs (see proposed
§ 201.407(e)(4)).
e. ‘‘Net Contents.’’ The proposed rule
would require this section of the OTC
shipping labeling to have the heading
‘‘Net Contents,’’ followed by the
contents of the shipping carton (see
proposed § 201.407(e)(5)).
f. ‘‘Storage and Handling.’’ The
proposed rule would require this
section of the OTC shipping labeling to
have the heading ‘‘Storage and
Handling,’’ followed by drug storage
information (see proposed
§ 201.407(e)(6)). Also, any handling
information required for safe and
effective use of the new animal drug
would be included in this section.
Information on disposal of the new
animal drug would not be required to be
included on the OTC shipping labeling.
g. NADA/ANADA approval statement.
For approved new animal drugs or
approved generic new animal drugs, the
proposed rule would require this
section of the OTC shipping labeling to
include the NADA or ANADA approval
statement, as described in proposed
§ 201.405(a)(21) for full prescribing
information for Rx new animal drugs
(see proposed § 201.407(e)(7)).
h. Name and place of business. The
proposed rule would require this
section of the OTC shipping labeling to
identify the name and place of business
of the manufacturer, packer, or
distributor, as described in proposed
§ 201.405(a)(22) for full prescribing
information for Rx new animal drugs
(see proposed § 201.407(e)(8)).
i. ‘‘Lot Number and Expiration Date.’’
The proposed rule would require this
section of the OTC shipping labeling to
have the heading ‘‘Lot Number and
Expiration Date,’’ followed by the
identifying lot or control number(s) and
the expiration date(s) of the OTC new
animal drug within the shipping carton
(see proposed § 201.407(e)(9)). The
shipping carton may contain more than
one lot of the OTC new animal drug,
and therefore, more than one lot or
control number and expiration date may
be listed in this section of the OTC
shipping labeling.
j. ‘‘Revision Date.’’ The proposed rule
would require the last section of the
OTC shipping labeling to have the
heading ‘‘Revision Date,’’ followed by
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the date of the most recent revision of
the OTC shipping labeling, listing the
month followed by the year (see
proposed § 201.407(e)(10)).
6. Other Approved Labeling for OTC
New Animal Drugs (OTC Other
Approved Labeling) (Proposed
§ 201.407(f))
The proposed rule would establish
content and format requirements for the
information presented on other
approved labeling for approved or
conditionally approved OTC new
animal drugs (OTC other approved
labeling) (see proposed § 201.407(f)).
OTC other approved labeling includes,
but is not limited to, labeling on display
cartons and multi-unit cartons
(excluding shipping cartons), containing
the immediate containers or the
secondary containers of the OTC new
animal drug.
The proposed rule would require the
following information to be presented
on the OTC other approved labeling and
in the following order (see proposed
§ 201.407(f)). Unless otherwise
indicated, this information would be the
same as that required by proposed
§ 201.405(a) for full prescribing
information for approved or
conditionally approved Rx new animal
drugs or proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs.
a. Proprietary name of the finished
drug product. The proposed rule would
require this section of the OTC other
approved labeling to include the
proprietary name of the finished drug
product (see proposed § 201.407(f)(1)).
b. Established name of the drug
product. The proposed rule would
require this section of the OTC other
approved labeling to include the
established name of the drug product
(see proposed § 201.407(f)(2)).
c. Established name and strength or
concentration of each active ingredient.
The proposed rule would require this
section of the OTC other approved
labeling to provide the established name
and strength or concentration of each
active ingredient (see proposed
§ 201.407(f)(3)).
d. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the OTC other approved
labeling to include a conditional
approval statement, as described in
proposed § 201.405(a)(3) for full
prescribing information for Rx animal
drugs (see proposed § 201.407(f)(4)).
e. Extralabel use statement. The
proposed rule would require this
section of the OTC other approved
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labeling to include the extralabel use
statement as described in proposed
§ 201.407(a)(4) for full product
information (see proposed
§ 201.407(f)(5)).
f. Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use, in
accordance with § 530.41, the proposed
rule would require this section of the
OTC other approved labeling to include
the extralabel use prohibition statement,
as described in proposed § 201.405(a)(5)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(f)(6)).
g. ‘‘Net Contents.’’ The proposed rule
would require this section of the OTC
other approved labeling to have the
heading ‘‘Net Contents,’’ followed by
the contents of the container to which
the OTC other approved labeling applies
(see proposed § 201.407(f)(7)).
h. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the OTC other approved
labeling to have the heading ‘‘Storage,
Handling, and Disposal,’’ followed by
drug storage, handling, and disposal
information, as described in proposed
§ 201.405(a)(20) for full prescribing
information for Rx new animal drugs
(see proposed § 201.407(f)(8)).
i. NADA/ANADA approval statement.
For approved new animal drugs or
approved generic new animal drugs, the
proposed rule would require this
section of the OTC other approved
labeling to include the NADA or
ANADA approval statement, as
described in proposed § 201.405(a)(21)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.407(f)(9)).
j. Name and place of business. The
proposed rule would require this
section of the OTC other approved
labeling to identify the name and place
of business of the manufacturer, packer,
or distributor, as described in proposed
§ 201.405(a)(22) for full prescribing
information for Rx new animal drugs
(see proposed § 201.407(f)(10)).
k. ‘‘Lot Number and Expiration Date.’’
The proposed rule would require this
section of the OTC other approved
labeling to have the heading ‘‘Lot
Number and Expiration Date,’’ followed
by the identifying lot or control number
of the OTC new animal drug within the
container to which the OTC other
approved labeling applies. This section
of the OTC other approved labeling
would also be required to include the
expiration date of the OTC new animal
drug within the container to which the
OTC other approved labeling applies, in
accordance with § 201.17. In accordance
with § 201.17, the proposed rule would
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allow an expiration date to be excluded
from the OTC other approved labeling if
the expiration date provided on
containers within or their labeling is
easily legible through the container to
which the OTC other approved labeling
applies (see proposed § 201.407(f)(11)).
l. ‘‘Revision Date.’’ The proposed rule
would require the last section of the
OTC other approved labeling to have the
heading ‘‘Revision Date,’’ followed by
the date of the most recent revision of
the OTC other approved labeling, listing
the month followed by the year (see
proposed § 201.405(f)(12)).
F. Content and Format of Labeling for
New Animal Drugs for Use in Animal
Feeds—Overview (Proposed § 201.409)
The proposed rule provides content
and format requirements for all
components of labeling for approved or
conditionally approved new animal
drugs for use in animal feeds and that
are subject to part 558, including VFD
drugs. New animal drugs for use in
animal feeds are approved in
accordance with section 512 of the
FD&C Act or conditionally approved in
accordance with section 571 of the
FD&C Act (see proposed § 201.409).
Most combination new animal drugs are
currently approved for use in animal
feeds or drinking water in accordance
with section 512(d)(4) of the FD&C Act.
The majority of new animal drugs
approved or conditionally approved for
use in animal feeds are intended for use
in food-producing animals and to be fed
to multiple animals at one time.
As described above, proposed
§ 201.405 (‘‘Content and format for
prescription (Rx) new animal drug
labeling’’) would not apply to approved
or conditionally approved new animal
drugs intended for use in or on animal
feeds under the professional supervision
of a licensed veterinarian because, in
accordance with section 504(a) of the
FD&C Act, such drugs are approved or
conditionally approved as VFD drugs.
The proposed rule would establish the
content and format requirements for all
components of labeling for approved or
conditionally approved new animal
drugs intended for use in animal feeds
that are subject to part 558, including
VFD drugs (see proposed § 201.409).
The proposed rule would require that
labeling sections or subsections that do
not apply be omitted from the labeling
for approved or conditionally approved
new animal drugs for use in animal
feeds (see proposed § 201.409). For
example, new animal drugs approved or
conditionally approved for use in
animal feeds that are not VFD drugs
would not require a VFD cautionary
statement section.
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FDA determines the final content of
each applicable section of labeling
during the review of each new animal
drug as part of the approval process.
Sponsors of new animal drugs for use
in animal feeds often submit an
application for approval or conditional
approval of a ‘‘Type A medicated
article,’’ which is a concentrated form of
the drug intended solely for use in the
manufacture of another Type A
medicated article or medicated feeds
(i.e., ‘‘Type B medicated feeds’’ and/or
‘‘Type C medicated feeds,’’ see below),
The Type A medicated article consists
of a new animal drug(s), with or without
a carrier, with or without inactive
ingredients (see § 558.3(b)(2) (21 CFR
558.3(b)(2))).
Type B medicated feed is intended
solely for the manufacture of other
medicated feeds (Type B or Type C). It
serves as an intermediate medicated
feed not approved for feeding to the
target animals. It is manufactured by
diluting a Type A medicated article or
another Type B medicated feed with
non-medicated feed, and at least 25
percent of its weight is from nutritional
ingredients (see § 558.3(b)(3)). The
maximum approvable concentrations of
new animal drugs in Type B medicated
feeds must be established in accordance
with § 558.3(b)(3). The specific
maximum concentrations for approved
new animal drugs in Type B medicated
feeds are listed in § 558.4(d).
Type C medicated feed is fed directly
to target animals. It may also be used in
the manufacture of another Type C
medicated feed. When fed directly to
target animals, it is intended to be the
animals’ complete feed or part of their
total diet. It is manufactured by diluting
a Type A medicated article, a Type B
medicated feed, or another Type C
medicated feed with non-medicated
feed, and it contains a substantial
quantity of nutritional ingredients (see
§ 558.3(b)(4)).
Labeling for new animal drugs
intended for use in feed must be
included in the new animal drug
application (see § 514.1(b)(3)(v)). Such
labeling may include a Type A
medicated article label, representative
labeling for Type B and Type C
medicated feeds containing the new
animal drug, proprietary labeling for
Type B or Type C medicated feeds, and/
or other approved labeling associated
with the Type A medicated article.
Proposed § 201.409(a) identifies the
information that would be required to
be included on Type A medicated
article labels. A Type A medicated
article label is on the immediate
container, which is typically a bag. The
Type A medicated article label provides
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all information necessary for the safe
and effective use of the new animal
drug.
Similar to the labeling of other
approved or conditionally approved
new animal drugs, the Type A
medicated article label includes product
and manufacturer, packer or distributor
identification, approved or
conditionally approved indications for
use, warnings, and directions for use. In
addition, the directions for use for a
Type A medicated article must include
mixing directions for the manufacture of
medicated feeds from the Type A
medicated article, as well as feeding
directions for the finished Type C
medicated feeds manufactured from the
Type A medicated article (see
§ 514.1(b)(3)(v)(a)).
Proposed § 201.409(b) and (c) identify
the information that would be required
to be included on representative Type B
medicated feed labeling and
representative Type C medicated feed
labeling, respectively. Sponsors of a
Type A medicated article must include
in their application representative
labeling proposed for use in
manufacturing Type B and Type C
medicated feeds containing the new
animal drug (see § 514.1(b)(3)(v)(b)).
FDA approves or conditionally approves
the use of the Type A medicated article
to manufacture Type B and Type C
medicated feeds and also approves or
conditionally approves the Type A
medicated article label and the
representative labeling for the Type B
and Type C medicated feeds.
Representative Type B and Type C
medicated feed labeling is template
labeling approved by FDA as part of an
NADA or CNADA for a Type A
medicated article. Representative Type
B and Type C medicated feed labeling
approved in the NADA or CNADA
provide feed mills the minimal
information that must be included on
the final printed labels prepared for the
respective Type B and Type C
medicated feeds manufactured
containing the Type A medicated article
to provide for safe and effective use of
the new animal drug for its approved or
conditionally approved indication(s) for
use. FDA also uses the term ‘‘Blue Bird
labels’’ to refer to representative Type B
and Type C medicated feed labeling (see
64 FR 63195 at 63197, November 19,
1999).
Because the approved or
conditionally approved Type C
medicated feeds will be used as part of
the diet, or as the complete diet, of the
target animals, the representative Type
B and Type C medicated labeling also
provide for the nutritional requirements
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or content to be specified in the final
printed labels for the medicated feed.
If a final printed label for a Type B or
Type C medicated feed fails to conform
to the approved representative Type B
or Type C medicated feed labeling, the
medicated feed will be deemed unsafe,
in accordance with section 512(a)(2) of
the FD&C Act, and adulterated, in
accordance with section 501(a)(6) of the
FD&C Act.
If Type A medicated article(s) are
approved or conditionally approved for
more than one indication and/or target
animal, the concentration of the new
animal drug(s) may differ in the
medicated feed approved or
conditionally approved for these
indication(s) and/or target animal(s).
Also, the nutritional requirements or
content specified in the representative
labeling for the medicated feeds may
vary for different target animals. These
applications for Type A medicated
articles may include representative
Type B medicated feed labeling and
representative Type C medicated feed
labeling for each of the approved uses.
Some Type A medicated articles are
approved or conditionally approved to
be manufactured only directly into Type
C medicated feeds. In addition to the
Type A medicated article label, the
applications for these Type A medicated
articles must provide representative
labeling only for Type C medicated
feeds.
If new animal drugs for use in animal
feeds or drinking water are approved for
combination use, in accordance with
section 512(d)(4) of the FD&C Act, these
‘‘combination new animal drugs’’
generally provide for more than one
approved Type A medicated article to
be mixed into medicated feed or
drinking water for the approved target
animal. The only labeling approved for
such combination new animal drugs is
representative labeling for the
medicated feeds that combines
information from the representative
labeling of each individual Type A
medicated article. Combination new
animal drugs exclude conditionally
approved drugs subject to section 571 of
the FD&C Act. Section 512(d)(4) of the
FD&C Act was amended as part of the
MUMS Act of 2004 to clarify that only
products approved under section
512(b)(1) of the FD&C Act can be used
in new animal drug combinations.
Proposed § 201.409(f) identifies the
information that would be required to
be included on other approved labeling
for Type A medicated articles. Other
approved labeling for Type A medicated
articles may include shipping labeling
associated with shipment of bags of the
Type A medicated article.
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Proposed § 201.409(d) identifies the
information that would be required to
be included on proprietary Type B
medicated feed labels. In addition to
approving or conditionally approving
applications for Type A medicated
articles, FDA may also approve or
conditionally approve applications for
proprietary final formulations of Type B
medicated feeds. A proprietary Type B
medicated feed is intended solely for
the manufacture of Type C medicated
feeds or other Type B medicated feeds
and is not approved or conditionally
approved for feeding to the target
animals. For some proprietary Type B
medicated feeds, the formulation and
labeling are approved in an NADA or
CNADA. In other situations, the
underlying data and labeling for the
proprietary Type B medicated feed to
support the approved uses are
maintained in a VMF. For example, this
would include situations in which a
proprietary Type B medicated feed is
manufactured via modification to an
approved formulation published in the
CFR or where a feed manufacturer
creates its own proprietary formulation.
The application for a proprietary Type
B medicated feed will include the
proprietary label for the final Type B
medicated feed and representative Type
C medicated feed labeling that directs
the preparation of final printed labels
for Type C medicated feeds
manufactured from the proprietary Type
B medicated feed. Applications for
proprietary final formulations of Type B
medicated feeds will not include a Type
A medicated article label.
Proposed § 201.409(e) identifies the
information that would be required to
be included on proprietary Type C
medicated feed labels. FDA may also
approve or conditionally approve
applications for proprietary final
formulations of Type C medicated feeds.
For some proprietary Type C medicated
feeds, the formulation and labeling are
approved in an NADA or CNADA. In
other situations, the underlying data
and labeling for the proprietary Type C
medicated feed to support the approved
uses are maintained in a VMF. For
example, this would include situations
in which a proprietary Type C
medicated feed is manufactured via
modification to an approved
formulation published in the CFR or
where a feed manufacturer creates its
own proprietary formulation. The
application for a proprietary Type C
medicated feed will include the
proprietary label for the final Type C
medicated feed.
Prior to the enactment of the ADAA,
new animal drugs for use in animal
feeds were approved almost exclusively
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for OTC use. The ADAA allowed for
approval or conditional approval of a
new type of new animal drugs for use
in or on animal feeds called the
‘‘veterinary feed directive drug’’ (VFD
drug). Although not identical, the use of
VFD drugs shares similar requirements
to the use of Rx new animal drugs.
A veterinarian may only issue a VFD
for use in animals under his or her
supervision or oversight in the course of
his or her professional practice, and in
compliance with all applicable
veterinary licensing and practice
requirements (see § 558.6(b) (21 CFR
558.6(b))). Information that must be
included in a VFD is in § 558.6(b).
In accordance with § 558.6(a)(6), the
following cautionary statement must
appear on all labeling and advertising
associated with a VFD drug: ‘‘Caution:
Federal law restricts medicated feed
containing this veterinary feed directive
(VFD) drug to use by or on the order of
a licensed veterinarian.’’
Some sections of proposed § 201.409
are patterned after sections of proposed
§ 201.405 for labeling of Rx new animal
drugs or proposed § 201.407 for labeling
of OTC new animal drugs. These
sections include the conditional
approval statement or NADA/ANADA
approval statement, indications for use,
warnings, and other information
associated with the effects of the new
animal drug. Other sections of proposed
§ 201.409 are uniquely associated with
medicated articles and feeds, such as
mixing directions, feeding directions,
and information on nutritional content.
The labeling sections and subsections
for new animal drugs for use in animal
feeds would not be numbered. Headings
of sections and subsections that would
be required to appear verbatim on
labeling are identified in the proposed
regulations in quotations. Similarly,
certain other labeling text would be
required to appear verbatim on labeling;
this text is also identified in the
proposed regulations in quotations.
The proposed rule would require the
labeling of approved or conditionally
approved new animal drugs for use in
animal feeds and that are subject to part
558 of this chapter to comply with other
applicable requirements in proposed
subpart H (see proposed § 201.409).
1. Type A Medicated Article Label
(Proposed § 201.409(a))
The proposed rule would establish
content and format requirements for the
Type A medicated article label for new
animal drugs approved or conditionally
approved for use in animal feeds (see
proposed § 201.409(a)). A Type A
medicated article is a concentrated form
of the new animal drug intended solely
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for use in the manufacture of another
Type A medicated article or Type B
medicated feeds and/or Type C
medicated feeds. As defined in
§ 558.3(b)(2), a Type A medicated article
consists of a new animal drug(s), with
or without a carrier, with or without
inactive ingredients. A Type A
medicated article label is on the
immediate container, which is typically
a bag.
The Type A medicated article label
provides all information necessary for
the safe and effective use of the new
animal drug.
The proposed rule would require the
following information to be presented
on the Type A medicated article label
for an approved or conditionally
approved new animal drug and in the
following order (see proposed
§ 201.409(a)). Unless otherwise
indicated, this information would be the
same as that required by proposed
§ 201.405(a) for full prescribing
information for approved or
conditionally approved Rx new animal
drugs or proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs.
a. Type A medicated article
identification. The proposed rule would
require this section of the Type A
medicated article label to include the
proprietary name, the established name
of the Type A medicated article, and the
phrase ‘‘Type A medicated article’’ or
‘‘Type A liquid medicated article,’’ as
applicable, if not included as part of the
established name of the Type A
medicated article (see proposed
§ 201.409(a)(1)).
b. VFD cautionary statement. For VFD
new animal drugs, the proposed rule
would require this section of the Type
A medicated article label to include the
following cautionary statement, in
accordance with § 558.6(a)(6): ‘‘Caution:
Federal law restricts medicated feed
containing this veterinary feed directive
(VFD) drug to use by or on the order of
a licensed veterinarian.’’ This statement
would be required to be displayed
prominently and conspicuously on the
Type A medicated article label (see
proposed § 201.409(a)(2)).
c. ‘‘For further manufacturing only.’’
The proposed rule would require this
section of the Type A medicated label
to include the statement, ‘‘For further
manufacturing only’’ (see proposed
§ 201.409(a)(3)). This statement would
indicate that the Type A medicated
article can only be used to manufacture
another Type A medicated article or a
medicated feed. A Type A medicated
article cannot be fed directly to animals.
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d. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the Type A medicated
article label to include a conditional
approval statement, as described in
proposed § 201.405(a)(3) for full
prescribing information for
conditionally approved Rx new animal
drugs (see proposed § 201.409(a)(4)).
e. ‘‘Indications for Use.’’ The
proposed rule would require this
section of the Type A medicated article
label to have the heading ‘‘Indications
for Use,’’ followed by the approved or
conditionally approved indication(s)
and target animal(s), as described in
proposed § 201.407(a)(3) for full product
information for OTC new animal drugs,
with the exception of the heading of the
section (see proposed § 201.409(a)(5)).
f. Extralabel use statement. The
proposed rule would require this
section of the Type A medicated article
label to include an extralabel use
statement (see proposed § 201.409(a)(6)).
Extralabel use of an approved new
animal drug or human drug in or on an
animal feed is not permitted (see section
512(a)(4) of the FD&C Act and part 530).
The required statement would be: ‘‘It is
a violation of Federal law to use other
than as directed in the labeling.’’ It is
important for the layperson and
veterinarian to know that it is a
violation of Federal law to use new
animal drugs in or on animal feeds in
an extralabel manner.
g. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the Type A
medicated article label to have the
heading ‘‘Active Ingredient’’ or ‘‘Active
Ingredients,’’ followed by the
established name and concentration of
each active ingredient in the Type A
medicated article (see proposed
§ 201.409(a)(7)). If the Type A
medicated article contains one active
ingredient, the proposed rule would
require this section of the Type A
medicated article label to be entitled
‘‘Active Ingredient.’’ If the Type A
medicated article contains more than
one active ingredient, the proposed rule
would require this section of the Type
A medicated article label to be entitled
‘‘Active Ingredients.’’ Including the
concentration of the active ingredient(s)
is critical so that feed manufacturers can
properly mix Type B and C medicated
feeds from the Type A medicated article
with the approved concentration(s) of
the active ingredient(s).
h. ‘‘Inactive Ingredients.’’ When
inactive ingredients are provided on the
Type A medicated article label, the
proposed rule would require they be
listed in the ‘‘Inactive Ingredients’’
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section in decreasing order of
predominance, by weight or
concentration, as described in proposed
§ 201.405(a)(6)(viii) for full prescribing
information for Rx new animal drugs
(see proposed § 201.409(a)(8)).
i. ‘‘Directions.’’ The proposed rule
would require this section of the Type
A medicated article label to have the
heading ‘‘Directions,’’ followed by the
directions for use of the Type A
medicated article (see proposed
§ 201.409(a)(9)). The ‘‘Directions’’
section of the Type A medicated article
label would include three subsections.
i. ‘‘Approved Concentration(s) of
[Active Ingredient or Active Moiety] in
Type C Medicated Feeds.’’ The
proposed rule would require the first
subsection of the ‘‘Directions’’ section of
the Type A medicated article label to
have the heading ‘‘Approved
Concentration(s) of [Active Ingredient or
Active Moiety] in Type C Medicated
Feeds,’’ followed by the approved
concentration(s) of each active
ingredient in Type C medicated feed(s)
to be manufactured from the Type A
medicated article for the approved or
conditionally approved indications for
use (see proposed § 201.409(a)(9)(i)). If
an active ingredient is a salt or other
noncovalent derivative, its
concentration in the Type A medicated
article in the ‘‘Active Ingredient’’ or
‘‘Active Ingredients’’ section (see
proposed § 201.409(a)(7)) may be
expressed on the basis of the full active
ingredient (i.e., including the salt or
other noncovalent derivative) or the
active moiety. If an active ingredient is
a salt or other noncovalent derivative
and its concentration in the Type A
medicated article was expressed in the
‘‘Active Ingredient’’ or Active
Ingredients’’ section based on the active
moiety, the proposed rule would require
the approved concentration(s) in the
Type C medicated feeds to also be
expressed based on the active moiety,
and the title of this subsection would be
required to include the name of the
active moiety instead of the active
ingredient (see proposed
§ 201.409(a)(9)(i)). Consistent expression
of the concentrations of active
ingredients on the Type A medicated
article label may reduce the risk of
mixing errors when manufacturing
medicated feeds from the Type A
medicated article.
Multiple Type C medicated feeds may
be approved or conditionally approved
for a Type A medicated article. Also,
different concentrations, or ranges of
concentrations, of the active ingredient
may be approved or conditionally
approved for different indications for
use. This subsection of the Type A
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medicated article label would clarify
this information for manufacturers of
medicated feeds manufactured from the
Type A medicated article.
ii. ‘‘Mixing Directions.’’ The proposed
rule would require this subsection of the
‘‘Directions’’ section of the Type A
medicated article label to have the
heading ‘‘Mixing Directions,’’ followed
by the approved mixing directions for
the manufacture of approved medicated
feeds from the Type A medicated article
for each approved or conditionally
approved indication for use (see
proposed § 201.409(a)(9)(ii)). An
intermediate mixing step (called
preblend step) is sometimes required to
manufacture medicated feeds from the
Type A medicated article. For example,
the Type A medicated article may need
to be preblended with a small amount
of one or more feed ingredients before
being added to the rest of the feed
ingredients to increase the uniformity of
the drug distribution in the finished
medicated feed. The directions for such
a preblend step would also be required
to be included in this subsection of the
Type A medicated article label.
iii. ‘‘Feeding Directions.’’ The
proposed rule would require the last
subsection in the ‘‘Directions’’ section of
the Type A medicated article label to
have the heading ‘‘Feeding Directions,’’
followed by the approved feeding
directions for each approved or
conditionally approved indication for
use for Type C medicated feeds
approved or conditionally approved to
be manufactured from the Type A
medicated article (see proposed
§ 201.409(a)(9)(iii)).
j. ‘‘Warnings.’’ The proposed rule
would require this section of the Type
A medicated article label for all
approved or conditionally approved
Type A medicated articles, and it would
have the heading ‘‘Warnings,’’ followed
by all warnings (see proposed
§ 201.409(a)(10)). This section of the
Type A medicated article label would
have the same subsections as described
in § 201.405(a)(10) in full prescribing
information for Rx new animal drugs,
except that the ‘‘Animal Safety
Warnings’’ subsection would be the
same as described in proposed
§ 201.407(a)(7)(iii) for full product
information for OTC new animal drugs.
k. ‘‘Additional Recommendations.’’
For new animal drugs having
precautions, the proposed rule would
require this section of the Type A
medicated article label to have the
heading ‘‘Additional
Recommendations,’’ followed by all
precautions (see proposed
§ 201.409(a)(11)). This section of the
Type A medicated article label would be
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the same as described in proposed
§ 201.407(a)(8) for full product
information for OTC new animal drugs.
For VFD new animal drugs, this section
would include precautions directed to
veterinarians as well as the layperson.
l. ‘‘Other Effects You May Notice.’’
For new animal drugs that have effects
on the target animal(s) that are not
considered contraindications, target
animal safety warnings, adverse
reactions, or post-approval adverse drug
experiences, and FDA determines that
these effects are required to be described
on labeling, the proposed rule would
require this section of the Type A
medicated article label to have the
heading ‘‘Other Effects You May
Notice,’’ followed by a description of
the effects (see proposed
§ 201.409(a)(12)). This section of the
Type A medicated article label would be
the same as described in proposed
§ 201.407(a)(9) for full product
information for OTC new animal drugs.
m. ‘‘Net Weight.’’ The proposed rule
would require this section of the Type
A medicated article label to have the
heading ‘‘Net Weight,’’ followed by the
net weight of the Type A medicated
article in the immediate container (see
proposed § 201.409(a)(13)).
n. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the Type A medicated article
label to have the heading ‘‘Storage,
Handling, and Disposal,’’ followed by
storage information for the Type A
medicated article, as well as any
required handling and disposal
information (see proposed
§ 201.409(a)(14)). This section of the
Type A medicated article label would be
the same as described in proposed
§ 201.405(a)(20) for full prescribing
information for Rx new animal drugs.
o. ‘‘Questions/Comments?’’ The
proposed rule would require this
section of the Type A medicated article
label to have the heading ‘‘Questions/
Comments?,’’ followed by the sponsor’s
contact information for feed
manufacturers or other users of the Type
A medicated article to facilitate
requesting additional information or to
report suspected adverse drug
experiences. FDA’s contact information
for voluntary reporting of adverse drug
experiences for animal drugs would also
be required (see proposed
§ 201.409(a)(15)). The ‘‘Questions/
Comments?’’ section of the Type A
medicated article label would be similar
to the ‘‘Questions/Comments?’’ section
in proposed § 201.407(a)(14) for full
product information for OTC new
animal drugs.
The sponsor’s contact information
would be the name of the manufacturer,
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packer, or distributor, whichever is
identified in the ‘‘Name and place of
business’’ section of the Type A
medicated article label (see proposed
§ 201.409(a)(17)). If more than one
business is identified in the ‘‘Name and
place of business’’ section of the Type
A medicated article label, the drug
sponsor would select the most
appropriate of these businesses to use in
the ‘‘Questions/Comments?’’ section to
provide additional information about
the Type A medicated article and to
contact regarding suspected adverse
drug experiences.
The statements in this section of the
Type A medicated article label would be
required to be structured as follows:
‘‘Contact [insert name of business] at
[insert business telephone number] or
[insert business web address]. To report
side effects, contact [insert name of
business] at [insert business telephone
number]. For additional information
about reporting side effects for animal
drugs, contact FDA at [insert current
FDA telephone number for voluntary
reporting of adverse drug experiences]
or [insert current FDA web address for
voluntary reporting of adverse drug
experiences].’’ Sponsors can search
FDA’s website or contact FDA by
telephone to find the current FDA
telephone number or web address for
voluntary reporting of adverse drug
experiences for animal drug.
p. NADA/ANADA approval
statement. For approved or generic
approved Type A medicated articles, the
proposed rule would require this
section of the Type A medicated article
label to include an ‘‘NADA approval
statement’’ or ‘‘ANADA approval
statement,’’ respectively (see proposed
§ 201.409(a)(16)). This section of the
Type A medicated article label would be
the same as described in proposed
§ 201.405(a)(21) for full prescribing
information for Rx new animal drugs.
q. Name and place of business. The
proposed rule would require this
section of the Type A medicated article
label to identify the name and place of
business of the manufacturer, packer, or
distributor (see proposed
§ 201.409(a)(17)). This section of the
Type A medicated article label would be
the same as described in proposed
§ 201.405(a)(22) for full prescribing
information for Rx new animal drugs.
r. ‘‘Lot Number and Expiration Date.’’
The proposed rule would require this
section of the Type A medicated article
label to have the heading ‘‘Lot Number
and Expiration Date,’’ followed by the
identifying lot or control number of the
Type A medicated article within the
immediate container. A lot or control
number would help us to more easily
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identify and trace back a specific lot of
a Type A medicated article should a
problem be reported to FDA (see
proposed § 201.409(a)(18)). In
accordance with § 226.58(d) of this
chapter, the proposed rule would also
require this section of the Type A
medicated article label to include the
expiration date of the Type A medicated
article within the immediate container.
An expiration date is important to
ensure the safe and effective use of
products.
Alternatively, the proposed rule
would allow for this section of the Type
A medicated article label to refer to the
location on the Type A medicated
article label or immediate container
where the lot or control number and
expiration date are printed (see
proposed § 201.409(a)(18)). As an
example, if the lot number and
expiration date are printed on the
bottom half of the back of the bag
containing the Type A medicated
article, then the Type A medicated
article label may state in this section,
‘‘See bottom back half of bag for lot
number and expiration date.’’
s. ‘‘Revision Date.’’ The proposed rule
would require this section of the Type
A medicated article label to have the
heading ‘‘Revision Date,’’ followed by
the date of the most recent revision of
the Type A medicated article label,
listing the month followed by the year
(see proposed § 201.409(a)(19)). This
information is important to ensure that
the most current approved version of
the Type A medicated article label is
being used.
2. Representative Type B Medicated
Feed Labeling (Proposed § 201.409(b))
The proposed rule would establish
content and format requirements for
representative Type B medicated feed
labeling for new animal drugs approved
or conditionally approved for use in
animal feeds (see proposed
§ 201.409(b)). A Type B medicated feed
is intended solely for the manufacture of
other medicated feeds (Type B or Type
C). It serves as an intermediate
medicated feed not approved for feeding
to the target animals. It is manufactured
by diluting a Type A medicated article
or another Type B medicated feed with
non-medicated feed, and at least 25
percent of its weight is from nutritional
ingredients (see § 558.3(b)(3)).
Representative Type B medicated feed
labeling is template labeling approved
by FDA as part of an NADA or CNADA
for a Type A medicated article.
Representative Type B medicated feed
labeling approved in the NADA or
CNADA provide feed mills the minimal
information that must be included on
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the final printed labels prepared for the
Type B medicated feeds manufactured
containing the Type A medicated article
to provide for safe and effective use of
the new animal drug for its approved or
conditionally approved indication(s) for
use.
The proposed rule would require the
following information to be presented
on the representative Type B medicated
feed labeling for an approved or
conditionally approved new animal
drug and in the following order (see
proposed § 201.409(b)). Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information for approved or
conditionally approved Rx new animal
drugs, proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs, or proposed § 201.409(a)
for the Type A medicated article label.
a. Description of the Type B
medicated feed. The proposed rule
would require this section of the
representative Type B medicated feed
labeling to provide a description of the
Type B medicated feed (see proposed
§ 201.409(b)(1)). This section of the
representative Type B medicated feed
labeling would serve as a placeholder
for the proprietary name of the final
Type B medicated feed to be added by
the feed manufacturer to the label of the
final Type B medicated feed
manufactured in accordance with the
approved representative Type B
labeling.
Representative Type B medicated
labeling may be approved or
conditionally approved for multiple
Type B medicated feeds within an
application. The proposed rule would
require the description of each approved
Type B medicated feed to distinguish it
from any other Type B medicated feeds
approved or conditionally approved
within the same application (see
proposed § 201.409(b)(1)(i)).
Distinguishing information may include
the animals and/or indications for use
for which Type C medicated feeds
manufactured from the Type B
medicated feed are approved or
conditionally approved and/or other
characteristics of the Type B medicated
feeds.
The proposed rule would require that
the description of the approved Type B
medicated feed not include the
proprietary name of a Type A medicated
article (see proposed § 201.409(b)(1)(ii)).
The proprietary name of a Type A
medicated article is specific to the Type
A medicated article; use of that
proprietary name in the description of a
Type B medicated feed may incorrectly
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imply that the Type B medicated feed is
a Type A medicated article.
b. Established name of the Type B
medicated feed. The proposed rule
would require this section of the
representative Type B medicated feed
labeling to include the established name
of the Type B medicated feed. The
established name of the Type B
medicated feed would include the
active moiety or active ingredient of
each new animal drug, as determined by
FDA, followed by an identifying
statement of either ‘‘Type B medicated
feed’’ or ‘‘Type B liquid medicated
feed,’’ as applicable (see proposed
§ 201.409(b)(2)). The identifying
statements also clearly designate the
medicated feeds as Type B (as opposed
to a Type C) medicated feeds. The
identifying statements also distinguish
Type B liquid medicated feeds from
other Type B medicated feeds, which is
important because Type B liquid
medicated feeds have unique approval
and labeling requirements (see § 558.5
(21 CFR 558.5)).
c. VFD cautionary statement. For VFD
new animal drugs, the proposed rule
would require this section of the
representative Type B medicated feed
labeling to provide the VFD cautionary
statement, in accordance with
§ 558.6(a)(6), as described in proposed
§ 201.409(a)(2) for the Type A
medicated article label (see proposed
§ 201.409(b)(3)).
d. ‘‘Do Not Feed Undiluted.’’ The
proposed rule would require this
section of the representative Type B
medicated feed labeling to state, ‘‘Do
Not Feed Undiluted’’ (see proposed
§ 201.409(b)(4)). This statement would
remind users that the Type B medicated
feed is not to be fed directly to animals.
e. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the representative Type B
medicated feed labeling to include a
conditional approval statement, as
described in proposed § 201.405(a)(3)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.409(b)(5)).
f. ‘‘Indications for Use.’’ The proposed
rule would require this section of the
representative Type B medicated feed
labeling to have the heading
‘‘Indications for Use,’’ followed by the
approved or conditionally approved
indications(s) and target animal(s), as
described in proposed § 201.407(a)(3)
for full product information for OTC
new animal drugs, with the exception of
the heading. In addition, this section of
the representative Type B medicated
feed labeling would include only the
indications for use applicable to the
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specific Type B medicated feed to
which the representative labeling
applies (see proposed § 201.409(b)(6)).
g. Extralabel use statement. The
proposed rule would require this
section of the representative Type B
medicated feed labeling to include an
extralabel use statement, as described in
proposed § 201.409(a)(6) for the Type A
medicated article label (see proposed
§ 201.409(b)(7)).
h. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the representative
Type B medicated feed labeling to have
the heading ‘‘Active Ingredient’’ or
‘‘Active Ingredients,’’ followed by the
established name and approved
concentration(s) of each active
ingredient (see proposed
§ 201.409(b)(8)). If the Type B medicated
feed contains one active ingredient, the
proposed rule would require this
section of the representative Type B
medicated feed labeling to be titled
‘‘Active Ingredient.’’ If the Type B
medicated feed contains more than one
active ingredient, the proposed rule
would require this section of the
representative Type B medicated feed
labeling to be titled ‘‘Active
Ingredients.’’ FDA approves a single
concentration or a range of
concentrations of each active ingredient
for Type B medicated feeds and their
representative Type B medicated feed
labeling. However, the final Type B
medicated feed label would only
include a single concentration of each
active ingredient. If a range of
concentrations of the active
ingredient(s) is approved or
conditionally approved for Type B
medicated feeds, the representative
Type B medicated feed labeling would
be required to include a footnote, placed
at the bottom of the page of the
representative Type B medicated feed
labeling containing the ‘‘Active
Ingredient’’ or ‘‘Active Ingredients’’
section, which instructs feed
manufacturers that the final printed
Type B medicated feed label must only
include a single concentration for each
active ingredient.
i. ‘‘Guaranteed Analysis.’’ The
proposed rule would require this
section of the representative Type B
medicated feed labeling to have the
heading ‘‘Guaranteed Analysis,’’
followed by the nutritional content
guarantees of the Type B medicated feed
appropriate for the approved target
animals in addition to any other
required specifications (see proposed
§ 201.409(b)(9)). The Type B medicated
feed will be used to make a Type C
medicated feed that will be included as
part of the target animals’ diet or serve
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as their complete diet. Therefore, the
feed manufacturer and user must be
aware of the nutritional content of the
Type B medicated feed to properly
balance the nutritional content of the
diet of the target animal. Without this
nutritional content information being
made available to the manufacturer and
user of the medicated feed, the animals’
diet may be imbalanced, e.g., either
under- or over-feeding critical nutrients,
which could be harmful to the health of
the target animals. For this reason,
information of this type may be
considered material under section
201(n) of the FD&C Act such that it
would be required to be disclosed on
the representative Type B feed labeling.
Additional specifications may also be
required in this section of the
representative Type B medicated feed
labeling, such as the range of pH and/
or range of percent dry matter. For
example, the pH and/or ratio of dry
matter to moisture (expressed as percent
dry matter) of a liquid medicated feed
may affect the stability of the new
animal drug(s) it contains, such that a
specific Type B liquid medicated feed
would be approved only within a
specific range of pH and/or percent dry
matter (see § 558.5(d)(1) and (2)).
j. ‘‘Ingredients.’’ The proposed rule
would require this section of the
representative Type B medicated feed
labeling to have the heading
‘‘Ingredients,’’ followed by information
relative to feed ingredients (see
proposed § 201.409(b)(10)). This
information would include a statement
that the feed ingredients must be listed
on each final printed Type B medicated
feed label by their common or usual
names in descending order of
predominance by weight, in accordance
with § 501.4(a) (21 CFR 501.4(a)),
including their collective names where
permitted, in accordance with
§ 501.4(b)(13). Also included would be
a statement that spices, flavorings,
colorings, and chemical preservatives, if
used, must be declared on each final
printed Type B medicated feed label, in
accordance with § 501.22 (21 CFR
501.22).
k. ‘‘Mixing Directions.’’ The proposed
rule would require this section of the
representative Type B medicated feed
labeling to have the heading ‘‘Mixing
Directions,’’ followed by approved
mixing directions for the manufacture of
a Type C medicated feed(s) or another
Type B medicated feed(s), as applicable,
from the Type B medicated feed for
which the representative Type B
medicated feed labeling applies (see
proposed § 201.409(b)(11)).
l. ‘‘Warnings.’’ The proposed rule
would require this section of the
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representative Type B medicated feed
labeling to have the heading
‘‘Warnings,’’ followed by the
‘‘Warnings’’ section, as described in
proposed § 201.409(a)(10) for the Type
A medicated article label. In addition,
this section of the representative Type B
medicated feed labeling would include
only the warnings applicable to the
specific Type B medicated feed to
which the representative labeling
applies (see proposed § 201.409(b)(12)).
m. ‘‘Additional Recommendations.’’
For new animal drugs having
precautions, the proposed rule would
require this section of the representative
Type B medicated feed labeling to have
the heading ‘‘Additional
Recommendations,’’ followed by the
precautions, as described in proposed
§ 201.407(a)(8) for full product
information for OTC new animal drugs.
In addition, this section of the
representative Type B medicated feed
labeling would include only the
precautions applicable to the specific
Type B medicated feed to which the
representative labeling applies (see
proposed § 201.409(b)(13)).
n. ‘‘Other Effects You May Notice.’’
For new animal drugs that have effects
on the target animal(s) that are not
considered contraindications, target
animal safety warnings, adverse
reactions, or post-approval adverse drug
experiences, and FDA determines that
these effects are required to be described
on labeling, the proposed rule would
require this section of the representative
Type B medicated feed labeling to have
the heading ‘‘Other Effects You May
Notice,’’ followed by a description of
the effects. This section of the
representative Type B medicated feed
labeling would be the same as described
in proposed § 201.407(a)(9) for full
product information for OTC new
animal drugs. In addition, this section of
the representative Type B medicated
feed labeling would include only
statements of other effects applicable to
the specific Type B medicated feed to
which the representative Type B
medicated feed labeling applies (see
proposed § 201.409(b)(14)).
o. Name and place of business. The
proposed rule would require this
section of the representative Type B
medicated feed labeling to provide for
identification of the name and place of
business of the manufacturer, packer, or
distributor of the final Type B
medicated feed on the final printed
Type B medicated feed label, in
accordance with § 501.5 (see proposed
§ 201.409(b)(15)).
p. ‘‘Net Weight.’’ The proposed rule
would require this section of the
representative Type B medicated feed
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labeling to have the heading ‘‘Net
Weight,’’ followed by space to provide
for a statement on the final printed Type
B medicated feed label of the net weight
of the Type B medicated feed in the
immediate container (see proposed
§ 201.409(b)(16)).
q. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the representative Type B
medicated feed labeling to have the
heading ‘‘Storage, Handling, and
Disposal,’’ followed by storage
information for the Type B medicated
feed, as well as any required handling
and disposal information, as described
in proposed § 201.405(a)(20) for full
prescribing information for Rx new
animal drugs (see proposed
§ 201.409(b)(17)).
r. ‘‘Questions/Comments?’’ The
proposed rule would require this
section of the representative Type B
medicated feed labeling to have the
heading ‘‘Questions/Comments?,’’
followed by statements providing
contact information for use by feed
manufacturers or other users of the final
Type B medicated feed to request
additional information on the product
and/or to report problems with the
medicated feed (see proposed
§ 201.409(b)(18)). The first statement
would provide placeholders for the
name and contact information of the
business of the manufacturer, packer, or
distributor of the final Type B
medicated feed to later be inserted by
the business. The second statement
would provide FDA contact information
for reporting adverse drug experiences
for animal drugs and would be required
to be inserted by the sponsor of the new
animal drug application.
s. ‘‘Lot, Batch, or Control Number.’’
The proposed rule would require this
section of the representative Type B
medicated feed labeling to have the
heading ‘‘Lot, Batch, or Control
Number,’’ followed by space to provide
for an identifying lot, batch, or control
number on the final printed Type B
medicated feed label (see proposed
§ 201.409(b)(19)).
t. ‘‘Expiration Date.’’ For Type B
medicated feeds requiring an expiration
date, in accordance with
§ 514.1(b)(5)(x), the proposed rule
would require this section of the
representative Type B medicated feed
labeling to have the heading ‘‘Expiration
Date,’’ followed by space to provide for
the expiration date to be printed on the
final printed Type B medicated feed
label. In addition, the approved
expiration period would need to be
included in this section of the
representative Type B medicated feed
labeling (see proposed § 201.409(b)(20)).
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u. ‘‘Revision Date.’’ The proposed rule
would require this section of the
representative Type B medicated feed
labeling to have the heading ‘‘Revision
Date,’’ followed by the date of the most
recent revision of the representative
Type B medicated feed labeling, listing
the month followed by the year (see
proposed § 201.409(b)(21)). This
information is important to ensure that
the most current approved version of
the representative Type B medicated
feed labeling is being used.
3. Representative Type C Medicated
Feed Labeling (Proposed § 201.409(c))
The proposed rule would establish
content and format requirements for
representative Type C medicated feed
labeling for new animal drugs approved
or conditionally approved for use in
animal feeds (see proposed
§ 201.409(c)). Type C medicated feed is
fed directly to target animals. It may
also be used in the manufacture of
another Type C medicated feed. When
fed directly to target animals, it is
intended to be the animals’ complete
feed or part of their total diet. It is
manufactured by diluting a Type A
medicated article, a Type B medicated
feed, or another Type C medicated feed
with non-medicated feed, and it
contains a substantial quantity of
nutritional ingredients (see
§ 558.3(b)(4)).
Representative Type C medicated feed
labeling approved in the NADA or
CNADA provide feed mills the minimal
information that must be included on
the final printed labels prepared for the
Type C medicated feeds manufactured
containing the Type A medicated article
to provide for safe and effective use of
the new animal drug for its approved or
conditionally approved indication(s) for
use.
The proposed rule would require the
following information to be presented
on the representative Type C medicated
feed labeling for an approved or
conditionally approved new animal
drug and in the following order (see
proposed § 201.409(c)). Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information for approved or
conditionally approved Rx new animal
drugs, proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs, proposed § 201.409(a) for
the Type A medicated article label, or
proposed § 201.409(b) for representative
Type B medicated feed labeling.
a. Description of the Type C
medicated feed. The proposed rule
would require this section of the
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representative Type C medicated feed
labeling to provide a description of the
Type C medicated feed (see proposed
§ 201.409(c)(1)). This section of the
representative Type C medicated feed
labeling would serve as a placeholder
for the proprietary name of the final
Type C medicated feed to be added by
the feed manufacturer to the label of the
final Type C medicated feed
manufactured in accordance with the
approved representative Type C
labeling.
Representative Type C medicated
labeling may be approved or
conditionally approved for multiple
Type C medicated feeds within an
application. The proposed rule would
require the description of each approved
Type C medicated feed to distinguish it
from any other Type C medicated feeds
approved or conditionally approved
within the same application (see
proposed § 201.409(c)(1)(i)).
Distinguishing information may include
the animals and/or indications for use
for which Type C medicated feeds are
approved or conditionally approved
and/or other characteristics of the Type
C medicated feeds.
The proposed rule would require that
the description of the approved Type C
medicated feed not include the
proprietary name of a Type A medicated
article (see proposed § 201.409(c)(1)(ii)).
The proprietary name of a Type A
medicated article is specific to the Type
A medicated article; use of that
proprietary name in the description of a
Type C medicated feed may incorrectly
imply that the Type C medicated feed is
a Type A medicated article.
b. Established name of the Type C
medicated feed. The proposed rule
would require this section of the
representative Type C medicated feed
labeling to include the established name
of the Type C medicated. The
established name of the Type C
medicated feed would include the
active moiety or active ingredient of
each new animal drug, as determined by
FDA, followed by an identifying
statement of, ‘‘Type C medicated feed,’’
‘‘Type C liquid medicated feed,’’ ‘‘Type
C top-dress medicated feed,’’ ‘‘Type C
free-choice medicated feed,’’ or ‘‘Type C
liquid free-choice medicated feed,’’ as
applicable (see proposed
§ 201.409(c)(2)). The identifying
statements also clearly designate the
medicated feeds as Type C (as opposed
to a Type B) medicated feeds. The
identifying statements also distinguish
Type C liquid medicated feeds from
other Type C medicated feeds, which is
important because Type C liquid
medicated feeds have unique approval
and labeling requirements (see § 558.5).
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Similarly, Type C free-choice medicated
feeds have specific requirements for
their approval (see § 510.455 (21 CFR
510.455)).
c. VFD cautionary statement. For VFD
new animal drugs, the proposed rule
would require this section of the
representative Type C medicated feed
labeling to provide the VFD cautionary
statement, in accordance with
§ 558.6(a)(6), as described in proposed
§ 201.409(a)(2) for the Type A
medicated article label (see proposed
§ 201.409(c)(3)).
d. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the representative Type C
medicated feed labeling to include a
conditional approval statement, as
described in proposed § 201.405(a)(3)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.409(c)(4)).
e. ‘‘Indications for Use.’’ The
proposed rule would require this
section of the representative Type C
medicated feed labeling to have the
heading ‘‘Indications for Use,’’ followed
by the approved or conditionally
approved indications(s) and target
animal(s), as described in proposed
§ 201.407(a)(3) for full product
information for OTC new animal drugs,
with the exception of the heading. In
addition, this section of the
representative Type C medicated feed
labeling would include only the
indications for use applicable to the
specific Type C medicated feed to
which the representative labeling
applies (see proposed § 201.409(c)(5)).
f. Extralabel use statement. The
proposed rule would require this
section of the representative Type C
medicated feed labeling to include an
extralabel use statement, as described in
proposed § 201.409(a)(6) for the Type A
medicated article label (see proposed
§ 201.409(c)(6)).
g. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the representative
Type C medicated feed labeling to have
the heading ‘‘Active Ingredient’’ or
‘‘Active Ingredients,’’ followed by the
established name and approved
concentration(s) of each active
ingredient (see proposed
§ 201.409(c)(7)). If the Type C medicated
feed contains one active ingredient, the
proposed rule would require this
section of the representative Type C
medicated feed labeling to be entitled
‘‘Active Ingredient.’’ If the Type C
medicated feed contains more than one
active ingredient, the proposed rule
would require this section of the
representative Type C medicated feed
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labeling to be entitled ‘‘Active
Ingredients.’’ We approve a single
concentration or a range of
concentrations of each active ingredient
for Type C medicated feeds and their
representative Type C medicated feed
labeling. However, the final Type C
medicated feed label would only
include a single concentration of each
active ingredient. If a range of
concentrations of the active
ingredient(s) is approved or
conditionally approved for Type C
medicated feeds, the representative
Type C medicated feed labeling would
be required to include a footnote, placed
at the bottom of the page of the
representative Type C medicated feed
labeling containing the ‘‘Active
Ingredient’’ or ‘‘Active Ingredients’’
section, which instructs feed
manufacturers that the final printed
Type C medicated feed label must
include only a single concentration for
each active ingredient.
h. ‘‘Guaranteed Analysis.’’ The
proposed rule would require this
section of the representative Type C
medicated feed labeling to have the
heading ‘‘Guaranteed Analysis,’’
followed by the nutritional content
guarantees of the Type C medicated feed
and any other required specifications, as
described in proposed § 201.409(b)(9)
for representative Type B medicated
feed labeling (see proposed
§ 201.409(c)(8)).
i. ‘‘Ingredients.’’ The proposed rule
would require this section of the
representative Type C medicated feed
labeling to have the heading
‘‘Ingredients,’’ followed by information
relative to feed ingredients (see
proposed § 201.409(c)(9)).
For Type C medicated feeds that are
not Type C free-choice medicated feeds,
proposed § 201.409(b)(9)(i) would
require the heading to be followed by a
statement that the feed ingredients must
be listed on each final printed Type C
medicated feed label by their common
or usual names in descending order of
predominance by weight, in accordance
with § 501.4(a), including their
collective names where permitted, in
accordance with § 501.4(b)(13). Also
included would be a statement that
spices, flavorings, colorings, and
chemical preservatives, if used, must be
declared on the final printed Type C
medicated feed label, in accordance
with § 501.22.
For Type C free-choice medicated
feeds, the proposed rule would require
the heading to be followed by a listing
of the feed ingredients and their
inclusion rates, including the drug
concentrations exactly as they appear in
the approved non-proprietary formula
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published for the specific new animal
drug in part 558 (see proposed
§ 201.409(b)(9)(ii)).
j. ‘‘Feeding Directions.’’ The proposed
rule would require this section of the
representative Type C medicated feed
labeling to have the heading ‘‘Feeding
Directions,’’ followed by the approved
feeding directions (see proposed
§ 201.409(c)(10)). This section of
representative Type C medicated feed
labeling would include only the feeding
directions applicable to the specific
Type C medicated feed to which the
representative Type C medicated feed
labeling applies.
k. ‘‘Warnings.’’ The proposed rule
would require this section of the
representative Type C medicated feed
labeling to have the heading
‘‘Warnings,’’ followed by the
‘‘Warnings’’ section, as described in
proposed § 201.409(a)(10) for the Type
A medicated article label. In addition,
this section of the representative Type C
medicated feed labeling would include
only the warnings applicable to the
specific Type C medicated feed to
which the representative labeling
applies (see proposed § 201.409(c)(11)).
l. ‘‘Additional Recommendations.’’
For new animal drugs having
precautions, the proposed rule would
require this section of the representative
Type C medicated feed labeling to have
the heading ‘‘Additional
Recommendations,’’ followed by the
precautions, as described in proposed
§ 201.407(a)(8) for full product
information for OTC new animal drugs.
In addition, this section of the
representative Type C medicated feed
labeling would include only the
precautions applicable to the specific
Type C medicated feed to which the
representative labeling applies (see
proposed § 201.409(c)(12)).
m. ‘‘Other Effects You May Notice.’’
For new animal drugs that have effects
on the target animal(s) that are not
considered contraindications, target
animal safety warnings, adverse
reactions, or post-approval adverse drug
experiences, and FDA determines that
these effects are required to be described
on labeling, the proposed rule would
require this section of the representative
Type C medicated feed labeling to have
the heading ‘‘Other Effects You May
Notice,’’ followed by a description of
the effects. This section of the
representative Type C medicated feed
labeling would be the same as described
in proposed § 201.407(a)(9) for full
product information for OTC new
animal drugs. In addition, this section of
the representative Type C medicated
feed labeling would include only
statements of other effects applicable to
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the specific Type C medicated feed to
which the representative Type C
labeling applies (see proposed
§ 201.409(c)(13)).
n. Name and place of business. The
proposed rule would require this
section of the representative Type C
medicated feed labeling to provide for
identification of the name and place of
business of the manufacturer, packer, or
distributor of the final Type C
medicated feed on the final printed
Type C medicated feed label, in
accordance with § 501.5 (see proposed
§ 201.409(c)(14)).
o. ‘‘Net Weight.’’ The proposed rule
would require this section of the
representative Type C medicated feed
labeling to have the heading ‘‘Net
Weight,’’ followed by space to provide
for a statement on the final printed Type
C medicated feed label of the net weight
of the Type C medicated feed in the
immediate container (see proposed
§ 201.409(c)(15)).
p. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the representative Type C
medicated feed labeling to have the
heading ‘‘Storage, Handling, and
Disposal,’’ followed by storage
information for the Type C medicated
feed, as well as any required, handling
and disposal information, as described
in proposed § 201.405(a)(20) for full
prescribing information for Rx new
animal drugs (see proposed
§ 201.409(c)(16)).
q. ‘‘Questions/Comments?’’ The
proposed rule would require this
section of the representative Type C
medicated feed labeling to have the
heading ‘‘Questions/Comments?,’’
followed by statements providing
contact information for use by feed
manufacturers or other users of the final
Type C medicated feed to request
additional information on the product
and/or to report problems with the
medicated feed (see proposed
§ 201.409(c)(17)). The first statement
would provide placeholders for the
name and contact information of the
business of the manufacturer, packer, or
distributor of the final Type C
medicated feed to later be inserted by
the business. The second statement
would provide FDA contact information
for reporting adverse drug experiences
for animal drugs and would be required
to be inserted by the sponsor of the new
animal drug application.
r. ‘‘Lot, Batch, or Control Number.’’
The proposed rule would require this
section of the representative Type C
medicated feed labeling to have the
heading ‘‘Lot, Batch, or Control
Number,’’ followed by space to provide
for an identifying lot, batch, or control
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number on the final printed Type C
medicated feed label (see proposed
§ 201.409(c)(19)).
s. ‘‘Expiration Date.’’ For Type C
medicated feeds requiring an expiration
date, in accordance with
§ 514.1(b)(5)(x), the proposed rule
would require this section of the
representative Type C medicated feed
labeling to have the heading ‘‘Expiration
Date,’’ followed by space to provide for
the expiration date to be printed on the
final printed Type C medicated feed
label. In addition, the approved
expiration period would need to be
included in this section of the
representative Type C medicated feed
labeling (see proposed § 201.409(c)(19)).
t. ‘‘Revision Date.’’ The proposed rule
would require this section of the
representative Type C medicated feed
labeling to have the heading ‘‘Revision
Date,’’ followed by the date of the most
recent revision of the representative
Type C medicated feed labeling, listing
the month followed by the year (see
proposed § 201.409(c)(20)). This
information is important to ensure that
the most current approved version of
the representative Type C medicated
feed labeling is being used.
4. Proprietary Type B Medicated Feed
Label (Proposed § 201.409(d))
The proposed rule would establish
content and format requirements for a
proprietary Type B medicated feed label
for new animal drugs approved or
conditionally approved for use in
animal feeds (see proposed
§ 201.409(d)). A proprietary Type B
medicated feed is intended solely for
the manufacture of Type C medicated
feeds or other Type B medicated feeds
and is not approved or conditionally
approved for feeding to the target
animals. For some proprietary Type B
medicated feeds, the formulation and
labeling are approved in an NADA. In
other situations, the underlying data
and labeling for the proprietary Type B
medicated feed to support the approved
uses are maintained in a VMF. For
example, this would include situations
in which a proprietary Type B
medicated feed is manufactured via
modification to an approved
formulation published in the CFR or
where a feed manufacturer creates its
own proprietary formulation. The
application for a proprietary Type B
medicated feed will include the
proprietary label for the final Type B
medicated feed and representative Type
C medicated feed labeling that directs
the preparation of final printed labels
for Type C medicated feeds
manufactured from the proprietary Type
B medicated feed. A proprietary Type B
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medicated feed label is on the
immediate container, which is typically
a bag or bulk container.
The proposed rule would require the
following information to be presented
on the proprietary Type B medicated
feed label for an approved or
conditionally approved new animal
drug and in the following order (see
proposed § 201.409(d)). Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information for approved or
conditionally approved Rx new animal
drugs, proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs, or proposed § 201.409(a)
for the Type A medicated article label.
a. Proprietary Type B medicated feed
identification. The proposed rule would
require this section of the proprietary
Type B medicated feed label to identify
the Type B medicated feed (see
proposed § 201.409(d)(1)). This section
of the proprietary Type B medicated
feed label would be required to include
the following components in order:
i. Proprietary name of the Type B
medicated feed. The proposed rule
require this subsection of the
proprietary Type B medicated feed label
to include the proprietary name of the
Type B medicated feed (see proposed
§ 201.409(d)(1)(i)).
ii. Established name of the Type B
medicated feed. The proposed rule
would require this subsection of the
proprietary Type B medicated feed label
to include the established name of the
Type B medicated feed. The established
name of the Type B medicated feed
would include the active moiety or
active ingredient of each new animal
drug, as determined by FDA, followed
by an identifying statement of either
‘‘Type B medicated feed’’ or ‘‘Type B
liquid medicated feed,’’ as applicable
(see proposed § 201.409(d)(1)(ii)). The
identifying statements also clearly
designate the medicated feed as a Type
B (as opposed to a Type C) medicated
feed. The identifying statements also
distinguish Type B liquid medicated
feeds from other Type B medicated
feeds, which is important because Type
B liquid medicated feeds have unique
approval and labeling requirements (see
§ 558.5).
b. VFD cautionary statement. For VFD
new animal drugs, the proposed rule
would require this section of the
proprietary Type B medicated feed label
to provide the VFD cautionary
statement, in accordance with
§ 558.6(a)(6), as described in proposed
§ 201.409(a)(2) for the Type A
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18303
medicated article label (see proposed
§ 201.409(d)(2)).
c. ‘‘Do Not Feed Undiluted.’’ The
proposed rule would require this
section of the proprietary Type B
medicated feed label to state, ‘‘Do Not
Feed Undiluted’’ (see proposed
§ 201.409(d)(3)). This statement would
remind users that the Type B medicated
feed is not to be fed directly to animals.
d. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the proprietary Type B
medicated feed label to include a
conditional approval statement, as
described in proposed § 201.405(a)(3)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.409(d)(4)).
e. ‘‘Indications for Use.’’ The
proposed rule would require this
section of the proprietary Type B
medicated feed label to have the
heading ‘‘Indications for Use,’’ followed
by the approved or conditionally
approved indications(s) and target
animal(s), as described in proposed
§ 201.407(a)(3) for full product
information for OTC new animal drugs,
with the exception of the heading (see
proposed § 201.409(d)(5)).
f. Extralabel use statement. The
proposed rule would require this
section of the proprietary Type B
medicated feed label to include an
extralabel use statement, as described in
proposed § 201.409(a)(6) for the Type A
medicated article label (see proposed
§ 201.409(d)(6)).
g. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the proprietary
Type B medicated feed label to have the
heading ‘‘Active Ingredient’’ or ‘‘Active
Ingredients,’’ followed by the
established name and approved
concentration of each active ingredient
(see proposed § 201.409(d)(7)). If the
proprietary Type B medicated feed
contains one active ingredient, the
proposed rule would require this
section of the proprietary Type B
medicated feed label to be entitled
‘‘Active Ingredient.’’ If the proprietary
Type B medicated feed contains more
than one active ingredient, the proposed
rule would require this section of the
proprietary Type B medicated feed label
to be entitled ‘‘Active Ingredients.’’
Because the proprietary Type B
medicated feed label applies to a final
Type B medicated feed, a single
concentration would be required for
each active ingredient rather than a
range.
h. ‘‘Guaranteed Analysis.’’ The
proposed rule would require this
section of the proprietary Type B
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medicated feed label to have the
heading ‘‘Guaranteed Analysis,’’
followed by the nutritional content
guarantees and any other required
specifications for the proprietary Type B
medicated feed (see proposed
§ 201.409(d)(8)).
i. ‘‘Ingredients.’’ The proposed rule
would require this section of the
proprietary Type B medicated feed label
to have the heading ‘‘Ingredients,’’
followed by a listing of the feed
ingredients in the proprietary Type B
medicated feed. The feed ingredients
would be required to be listed by their
common or usual names in descending
order of predominance by weight, in
accordance with § 501.4(a), including
their collective names where permitted,
in accordance with § 501.4(b)(13) (see
proposed § 201.409(d)(9)(i)). Spices,
flavorings, colorings, and chemical
preservatives, if used, would be
required to be declared, in accordance
with § 501.22 (see proposed
§ 201.409(d)(9)(ii)).
j. ‘‘Mixing Directions.’’ The proposed
rule would require this section of the
proprietary Type B medicated feed label
to have the heading ‘‘Mixing
Directions,’’ followed by the approved
mixing directions for the manufacture of
a Type C medicated feed(s) or another
Type B medicated feed(s), if applicable,
from the proprietary Type B medicated
feed (see proposed § 201.409(d)(10)).
k. ‘‘Warnings.’’ The proposed rule
would require this section of the
proprietary Type B medicated feed label
to have the heading ‘‘Warnings,’’
followed by the ‘‘Warnings’’ section, as
described in proposed § 201.409(a)(10)
for the Type A medicated article label
(see proposed § 201.409(d)(11)).
l. ‘‘Additional Recommendations.’’
For new animal drugs having
precautions, the proposed rule would
require this section of the proprietary
Type B medicated feed label to have the
heading ‘‘Additional
Recommendations,’’ followed by all
precautions, as described in proposed
§ 201.407(a)(8) for full product
information for OTC new animal drugs
(see proposed § 201.409(d)(12)).
m. ‘‘Other Effects You May Notice.’’
For new animal drugs that have effects
on the target animal(s) that are not
considered contraindications, target
animal safety warnings, adverse
reactions, or post-approval adverse drug
experiences, and FDA determines that
these effects are required to be described
on labeling, the proposed rule would
require this section of the proprietary
Type B medicated feed label to have the
heading ‘‘Other Effects You May
Notice,’’ followed by a description of
the effects. This section of the
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proprietary Type B medicated feed label
would be the same as described in
proposed § 201.407(a)(9) for full product
information for OTC new animal drugs
(see proposed § 201.409(d)(13)).
n. ‘‘Net Weight.’’ The proposed rule
would require this section of the
proprietary Type B medicated feed label
to have the heading ‘‘Net Weight,’’
followed by the net weight of the Type
B medicated feed in the immediate
container (see proposed
§ 201.409(d)(14)).
o. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the proprietary Type B
medicated feed label to have the
heading ‘‘Storage, Handling, and
Disposal,’’ followed by storage
information for the Type B medicated
feed, as well as any required handling
and disposal information, as described
in proposed § 201.405(a)(20) for full
prescribing information for Rx new
animal drugs (see proposed
§ 201.409(d)(15)).
p. ‘‘Questions/Comments?’’ The
proposed rule would require this
section of the proprietary Type B
medicated feed label to have the
heading ‘‘Questions/Comments?,’’
followed by the sponsor’s contact
information for feed manufacturers or
other users of the Type B medicated
feed to facilitate requesting additional
information on the product or to report
suspected adverse drug experiences.
FDA’s contact information for voluntary
reporting of adverse drug experiences
for animal drugs would also be required
(see proposed § 201.409(d)(16)).
The sponsor’s contact information
would be the name of the manufacturer,
packer, or distributor, whichever is
identified in the ‘‘Name and place of
business’’ section of the Type B
medicated feed (see proposed
§ 201.409(d)(18)). If more than one
business is identified in the ‘‘Name and
place of business’’ section of the
proprietary Type B medicated feed
label, the drug sponsor would select the
most appropriate of these businesses to
use in the ‘‘Questions/Comments?’’
section to provide additional
information about the Type B medicated
feed and to contact regarding suspected
adverse drug experiences.
The statements in this section of the
proprietary Type B medicated feed label
would be required to be structured as
follows: ‘‘Contact [insert name of
business] at [insert business telephone
number] or [insert business web
address]. To report side effects, contact
[insert name of business] at [insert
business telephone number]. For
additional information about reporting
problems with medicated feeds, contact
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FDA at [insert current FDA telephone
number for voluntary reporting of
adverse drug experiences] or [insert
current FDA web address for voluntary
reporting of adverse drug experiences].’’
Sponsors can search FDA’s website or
contact FDA by telephone to find the
current FDA telephone number or web
address for voluntary reporting of
adverse drug experiences for animal
drug.
q. NADA/ANADA approval
statement. For approved or generic
approved proprietary Type B medicated
feeds, the proposed rule would require
this section of the proprietary Type B
medicated feed label to include an
‘‘NADA approval statement’’ or
‘‘ANADA approval statement,’’
respectively, as described in proposed
§ 201.405(a)(21) for full prescribing
information for Rx new animal drugs
(see proposed § 201.409(d)(17)).
r. Name and place of business. The
proposed rule would require this
section of the proprietary Type B
medicated feed label to identify name
and place of business of the
manufacturer, packer, or distributor, as
described in proposed § 201.405(a)(22)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.409(d)(18)).
s. ‘‘Lot, Batch, or Control Number.’’
The proposed rule would require this
section of the proprietary Type B
medicated feed label to have the
heading ‘‘Lot, Batch, or Control
Number,’’ followed by the identifying
lot, batch, or control number of the Type
B medicated feed. Alternatively, the
proposed rule would allow for this
section of the proprietary Type B
medicated feed label to refer to the
location on the proprietary Type B
medicated feed label or immediate
container where the lot, batch, or
control number is printed (see proposed
§ 201.409(d)(19)).
t. ‘‘Expiration Date.’’ For Type B
medicated feeds requiring an expiration
date, in accordance with
§ 514.1(b)(5)(x), the proposed rule
would require this section of the
proprietary Type B medicated feed label
to have the heading ‘‘Expiration Date,’’
followed by the expiration date of the
proprietary Type B medicated feed.
Alternatively, the proposed rule would
allow for this section of the proprietary
Type B medicated feed label to refer to
the location on the proprietary Type B
medicated feed label or immediate
container where the expiration date is
printed (see proposed § 201.409(d)(20)).
u. ‘‘Revision Date.’’ The proposed rule
would require this section of the
proprietary Type B medicated feed label
to have the heading ‘‘Revision Date,’’
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followed by the date of the most recent
revision of the proprietary Type B
medicated feed label, listing the month
followed by the year (see proposed
§ 201.409(d)(21)). This information is
important to ensure that the most
current approved version of the
proprietary Type B medicated feed label
is being used.
5. Proprietary Type C Medicated Feed
Label (Proposed § 201.409(e))
The proposed rule would establish
content and format requirements for a
proprietary Type C medicated feed label
for new animal drugs approved or
conditionally approved for use in
animal feeds (see proposed
§ 201.409(e)). FDA may approve or
conditionally approve applications for
proprietary final formulations of Type C
medicated feeds. For some proprietary
Type C medicated feeds, the
formulation and labeling are approved
in an NADA. In other situations, the
underlying data and labeling for the
proprietary Type C medicated feed to
support the approved uses are
maintained in a VMF. For example, this
would include situations in which a
proprietary Type C medicated feed is
manufactured via modification to an
approved formulation published in the
CFR or where a feed manufacturer
creates its own proprietary formulation.
The application for a proprietary Type
C medicated feed will include the
proprietary label for the final Type C
medicated feed. A proprietary Type C
medicated feed label is on the
immediate container, which is typically
a bag or bulk container.
The proposed rule would require the
following information to be presented
on the proprietary Type C medicated
feed label for an approved or
conditionally approved new animal
drug and in the following order (see
proposed § 201.409(e)). Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information for approved or
conditionally approved Rx new animal
drugs, proposed § 201.407(a) for full
product information for approved or
conditionally approved OTC new
animal drugs, proposed § 201.409(a) for
the Type A medicated article label, or
proposed § 201.409(d) for the
proprietary Type B medicated feed
label.
a. Proprietary Type C medicated feed
identification. The proposed rule would
require this section of the proprietary
Type C medicated feed label to identify
the Type C medicated feed (see
proposed § 201.409(e)(1)). This section
of the proprietary Type C medicated
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feed label would be required to include
the following components in order:
i. Proprietary name of the Type C
medicated feed. The proposed rule
would require this subsection of the
proprietary Type C medicated feed label
to include the proprietary name of the
Type C medicated feed (see proposed
§ 201.409(e)(1)(i)).
ii. Established name of the Type C
medicated feed. The proposed rule
would require this subsection of the
proprietary Type C medicated feed label
to include the established name of the
Type C medicated feed. The established
name of the proprietary Type C
medicated feed would include the
active moiety or active ingredient of
each new animal drug, as determined by
FDA, followed by an identifying
statement of, ‘‘Type C medicated feed,’’
‘‘Type C liquid medicated feed,’’ ‘‘Type
C top-dress medicated feed,’’ ‘‘Type C
free-choice medicated feed,’’ or ‘‘Type C
liquid free-choice medicated feed,’’ as
applicable (see proposed
§ 201.409(e)(1)(ii)). The identifying
statements also clearly designate the
medicated feeds as Type C (as opposed
to a Type B) medicated feeds. The
identifying statements also distinguish
Type C liquid medicated feeds from
other Type C medicated feeds, which is
important because Type C liquid
medicated feeds have unique approval
and labeling requirements (see § 558.5).
Similarly, Type C free-choice medicated
feeds have specific requirements for
their approval (see § 510.455).
b. VFD cautionary statement. For VFD
new animal drugs, the proposed rule
would require this section of the
proprietary Type C medicated feed label
to provide the VFD cautionary
statement, in accordance with
§ 558.6(a)(6), as described in proposed
§ 201.409(a)(2) for the Type A
medicated article label (see proposed
§ 201.409(e)(2)).
c. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the proprietary Type C
medicated feed label to include a
conditional approval statement, as
described in proposed § 201.405(a)(3)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.409(e)(3)).
d. ‘‘Indications for Use.’’ The
proposed rule would require this
section of the proprietary Type C
medicated feed label to have the
heading ‘‘Indications for Use,’’ followed
by the approved or conditionally
approved indications(s) and target
animal(s), as described in proposed
§ 201.407(a)(3) for full product
information for OTC new animal drugs,
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18305
with the exception of the heading (see
proposed § 201.409(e)(4)).
e. Extralabel use statement. The
proposed rule would require this
section of the proprietary Type C
medicated feed label to include an
extralabel use statement, as described in
proposed § 201.409(a)(6) for the Type A
medicated article label (see proposed
§ 201.409(e)(5)).
f. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the proprietary
Type C medicated feed label to have the
heading ‘‘Active Ingredient,’’ or ‘‘Active
Ingredients,’’ followed by the
established name and approved
concentration of each active ingredient
(see proposed § 201.409(e)(6)). If the
proprietary Type C medicated feed
contains one active ingredient, the
proposed rule would require this
section of the proprietary Type C
medicated feed label to be entitled
‘‘Active Ingredient.’’ If the proprietary
Type C medicated feed contains more
than one active ingredient, the proposed
rule would require this section of the
proprietary Type C medicated feed label
to be entitled ‘‘Active Ingredients.’’
Because the proprietary Type C
medicated feed label applies to a final
Type C medicated feed, a single
concentration would be required for
each active ingredient rather than a
range.
g. ‘‘Guaranteed Analysis.’’ The
proposed rule would require this
section of the proprietary Type C
medicated feed label to have the
heading ‘‘Guaranteed Analysis,’’
followed by the nutritional content
guarantees and other required
specifications for the final proprietary
Type C medicated feed, as described in
§ 201.409(d)(8) for the proprietary Type
B medicated feed label (see proposed
§ 201.409(e)(7)).
h. ‘‘Ingredients.’’ The proposed rule
would require this section of the
proprietary Type C medicated label to
have the heading ‘‘Ingredients,’’
followed by a listing of the feed
ingredients in the proprietary Type C
medicated feed, as described in
§ 201.409(d)(9) for the proprietary Type
B medicated feed label (see proposed
§ 201.409(e)(8)).
i. ‘‘Feeding Directions.’’ The proposed
rule would require this section of the
proprietary Type C medicated feed label
to have the heading ‘‘Feeding
Directions,’’ followed by the approved
feeding directions (see proposed
§ 201.409(e)(9)).
j. ‘‘Warnings.’’ The proposed rule
would require this section of the
proprietary Type C medicated feed label
to have the heading ‘‘Warnings,’’
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followed by the ‘‘Warnings’’ section, as
described in proposed § 201.409(a)(10)
for the Type A medicated article label
(see proposed § 201.409(e)(10)).
k. ‘‘Additional Recommendations.’’
For new animal drugs having
precautions, the proposed rule would
require this section of the proprietary
Type C medicated feed label to have the
heading ‘‘Additional
Recommendations,’’ followed by all
precautions, as described in proposed
§ 201.407(a)(8) for full product
information for OTC new animal drugs
(see proposed § 201.409(e)(11)).
l. ‘‘Other Effects You May Notice.’’
For new animal drugs that have effects
on the target animal(s) that are not
considered contraindications, target
animal safety warnings, adverse
reactions, or post-approval adverse drug
experiences, and FDA determines that
these effects are required to be described
on labeling, the proposed rule would
require this section of the proprietary
Type C medicated feed label to have the
heading ‘‘Other Effects You May
Notice,’’ followed by a description of
the effects. This section of the
proprietary Type C label would be the
same as described in proposed
§ 201.407(a)(9) for full product
information for OTC new animal drugs
(see proposed § 201.409(e)(12)).
m. ‘‘Net Weight.’’ The proposed rule
would require this section of the
proprietary Type C medicated feed label
to have the heading ‘‘Net Weight,’’
followed by the net weight of the Type
C medicated feed in the immediate
container (see proposed
§ 201.409(e)(13)).
n. ‘‘Storage, Handling, and Disposal.’’
The proposed rule would require this
section of the proprietary Type C
medicated feed label to have the
heading ‘‘Storage, Handling, and
Disposal,’’ followed by storage
information for the Type C medicated
feed, as well as any required handling,
and disposal information, as described
in proposed § 201.405(a)(20) for full
prescribing information for Rx new
animal drugs (see proposed
§ 201.409(e)(14)).
o. ‘‘Questions/Comments?’’ The
proposed rule would require this
section of the proprietary Type C
medicated feed label to have the
heading ‘‘Questions/Comments?,’’
followed by the sponsor’s contact
information for users of the Type C
medicated feed to facilitate requesting
additional information on the product
or to report suspected adverse drug
experiences. FDA’s contact information
for voluntary reporting of adverse drug
experiences for animal drugs would also
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be required (see proposed
§ 201.409(e)(15)).
The sponsor’s contact information
would be the name of the manufacturer,
packer, or distributor, whichever is
identified in the ‘‘Name and place of
business’’ section of the Type C
medicated feed (see proposed
§ 201.409(e)(17)). If more than one
business is identified in the ‘‘Name and
place of business’’ section of the
proprietary Type C medicated feed
label, the drug sponsor would select the
most appropriate of these businesses to
use in the ‘‘Questions/Comments?’’
section to provide additional
information about the Type C medicated
feed and to contact regarding suspected
adverse drug experiences.
The statements in this section of the
proprietary Type C medicated feed label
would be required to be structured as
follows: ‘‘Contact [insert name of
business] at [insert business telephone
number] or [insert business web
address]. To report side effects, contact
[insert name of business] at [insert
business telephone number]. For
additional information about reporting
side effects or other problems with
medicated feeds, contact FDA at [insert
current FDA telephone number for
voluntary reporting of adverse drug
experiences] or [insert current FDA web
address for voluntary reporting of
adverse drug experiences].’’ Sponsors
can search FDA’s website or contact
FDA by telephone to find the current
FDA telephone number or web address
for voluntary reporting of adverse drug
experiences for animal drugs.
p. NADA/ANADA approval
statement. For approved or generic
approved proprietary Type C medicated
feeds, the proposed rule would require
this section of the proprietary Type C
medicated feed label to include an
‘‘NADA approval statement’’ or
‘‘ANADA approval statement,’’
respectively, as described in proposed
§ 201.405(a)(21) for full prescribing
information for Rx new animal drugs
(see proposed § 201.409(e)(16)).
q. Name and place of business. The
proposed rule would require this
section of the proprietary Type C
medicated feed label to identify name
and place of business of the
manufacturer, packer, or distributor, as
described in proposed § 201.405(a)(22)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.409(e)(17)).
r. ‘‘Lot, Batch, or Control Number.’’
The proposed rule would require this
section of the proprietary Type C
medicated feed label to have the
heading ‘‘Lot, Batch, or Control
Number,’’ followed by the identifying
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lot, batch, or control number of the Type
C medicated feed. Alternatively, the
proposed rule would allow for this
section of the proprietary Type C
medicated feed label to refer to the
location on the proprietary Type C
medicated feed label or immediate
container where the lot, batch, or
control number is printed (see proposed
§ 201.409(e)(18)).
s. ‘‘Expiration Date.’’ For Type C
medicated feeds requiring an expiration
date, in accordance with
§ 514.1(b)(5)(x), the proposed rule
would require this section of the
proprietary Type C medicated feed label
to have the heading ‘‘Expiration Date,’’
followed by the expiration date of the
proprietary Type C medicated feed.
Alternatively, the proposed rule would
allow for this section of the proprietary
Type C medicated feed label to refer to
the location on the proprietary Type C
medicated feed label or immediate
container where the expiration date is
printed (see proposed § 201.409(e)(19)).
t. ‘‘Revision Date.’’ The proposed rule
would require this section of the
proprietary Type C medicated feed label
to have the heading ‘‘Revision Date,’’
followed by the date of the most recent
revision of the proprietary Type C
medicated feed label, listing the month
followed by the year (see proposed
§ 201.409(e)(20)).
6. Other Approved Labeling for Type A
Medicated Articles (Proposed
§ 201.409(f))
The proposed rule would establish
content and format requirements for the
information presented on other
approved labeling for Type A medicated
articles approved or conditionally
approved for use in animal feeds. Other
approved labeling for Type A medicated
articles includes, but is not limited to,
labeling on shipping cartons containing
bags of Type A medicated articles (see
proposed § 201.409(f)).
The proposed rule would require the
following information to be presented
on other approved labeling for Type A
medicated articles and in the following
order (see proposed § 201.409(f)). Unless
otherwise indicated, this information
would be the same as that required by
proposed § 201.405(a) for full
prescribing information for approved or
conditionally approved Rx new animal
drugs, or proposed § 201.409(a) for a
Type A medicated article label.
a. Type A medicated article
identification. The proposed rule would
require this section of the other
approved labeling for Type A medicated
articles to include, in order, the
proprietary name and the established
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name of the Type A medicated article
(see proposed § 201.409(f)(1)).
b. VFD cautionary statement. For VFD
new animal drugs, the proposed rule
would require this section of the other
approved labeling for Type A medicated
articles to provide the VFD cautionary
statement, in accordance with
§ 558.6(a)(6), as described in proposed
§ 201.409(a)(2) for the Type A
medicated article label (see proposed
§ 201.409(f)(2)).
c. ‘‘Active Ingredient’’ or ‘‘Active
Ingredients.’’ The proposed rule would
require this section of the other
approved labeling for Type A medicated
articles to have the heading ‘‘Active
Ingredient’’ or ‘‘Active Ingredients,’’
followed by the established name and
concentration of each active ingredient
in the Type A medicated article. If the
Type A medicated article contains one
active ingredient, the proposed rule
would require this section of the other
approved labeling for Type A medicated
articles to be entitled ‘‘Active
Ingredient.’’ If the Type A medicated
article contains more than one active
ingredient, the proposed rule would
require this section of the other
approved labeling for Type A medicated
articles to be entitled ‘‘Active
Ingredients’’ (see proposed
§ 201.409(f)(3)).
d. Conditional approval statement.
For conditionally approved new animal
drugs, the proposed rule would require
this section of the other approved
labeling for Type A medicated articles
to include a conditional approval
statement, as described in proposed
§ 201.405(a)(3) for full prescribing
information for Rx new animal drugs
(see proposed § 201.409(f)(4)).
e. ‘‘Net Contents.’’ The proposed rule
would require this section of the other
approved labeling for Type A medicated
articles to have the heading ‘‘Net
Contents,’’ followed by the contents of
the container to which the other
approved labeling for Type A medicated
articles applies (see proposed
§ 201.409(f)(5)).
f. ‘‘Storage and Handling.’’ The
proposed rule would require this
section of the other approved labeling
for Type A medicated articles to have
the heading ‘‘Storage and Handling,’’
followed by storage information for the
Type A medicated article (see proposed
§ 201.409(f)(6)). Also, any handling
information required for safe and
effective use of the Type A medicated
article would be included in this
section. Information on disposal of the
Type A medicated article would not be
required to be included on other
approved labeling for Type A medicated
articles.
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g. NADA/ANADA approval statement.
For approved or generic approved
proprietary Type A medicated articles,
the proposed rule would require this
section of the other approved labeling
for Type A medicated articles to include
an ‘‘NADA approval statement’’ or
‘‘ANADA approval statement,’’
respectively, as described in proposed
§ 201.405(a)(21) for full prescribing
information for Rx new animal drugs
(see proposed § 201.409(f)(7)).
h. Name and place of business. The
proposed rule would require this
section of the other approved labeling
for Type A medicated articles to identify
name and place of business of the
manufacturer, packer, or distributor, as
described in proposed § 201.405(a)(22)
for full prescribing information for Rx
new animal drugs (see proposed
§ 201.409(f)(8)).
i. ‘‘Lot Number and Expiration Date.’’
The proposed rule would require this
section of the other approved labeling
for Type A medicated articles to have
the heading ‘‘Lot Number and
Expiration Date,’’ followed by the
identifying lot or control number(s) and
the expiration date(s) of the Type A
medicated article within the container
(see proposed § 201.409(f)(9)). The
container may include more than one
lot of the Type A medicated article, and
therefore, more than one lot or control
number and expiration date may be
listed in this section of other approved
labeling for Type A medicated articles.
j. ‘‘Revision Date.’’ The proposed rule
would require this section of the other
approved labeling for Type A medicated
articles to have the heading ‘‘Revision
Date,’’ followed by the date of the most
recent revision of the other approved
labeling for Type A medicated articles,
listing the month followed by the year
(see proposed § 201.409(f)(10)).
G. Exemptions From Labeling
Requirements for Approved or
Conditionally Approved New Animal
Drugs (Proposed § 201.411)
FDA would provide sponsors the
opportunity to request an exemption
from one or more specific requirements
set forth in this proposed subpart on the
basis that the requirements are not
appropriate for the specific approved or
conditionally approved new animal
drug (see proposed § 201.411).
An exemption request would be
required to be submitted to the
corresponding application or
investigational new animal drug file
(INAD) for the new animal drug. A
separate request would be required to be
submitted for each new animal drug for
which an exemption is sought. Requests
for exemptions would be granted or
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denied by the Director of FDA’s Center
for Veterinary Medicine or the Director’s
designee (see proposed § 201.411(a)).
The sponsor seeking an exemption
would be required to: (1) describe why
the particular requirement for which the
exemption is requested was not
appropriate for the new animal drug; (2)
describe why granting the exemption
would not adversely impact the safety
or effectiveness of the use of the new
animal drugs; and (3) include copies of
all draft labeling proposed to be used for
the new animal drug (see proposed
§ 201.411(b)). We anticipate that such
exemptions would be rare.
H. Labeling Requirements for Certain
Approved or Conditionally Approved
New Animal Drugs (Proposed § 201.413)
This section of the proposed
regulations would consolidate, and
where appropriate, update existing
labeling requirements pertaining to
certain approved or conditionally
approved new animal drugs that would
continue to apply in addition to the
other labeling requirements in proposed
subpart H. Currently, the labeling
requirements for these new animal
drugs are dispersed throughout the
regulations. It would be helpful to new
animal drug sponsors and FDA
reviewers if the proposed rule were to
consolidate, and where appropriate,
update the additional labeling
requirements for these specific new
animal drugs in the same subpart of the
CFR as general labeling requirements for
approved or conditionally approved
new animal drugs.
This section also proposes a new
labeling provision for all new animal
drugs approved or conditionally
approved for use in horses and
anthelmintic new animal drugs for
certain species of animals.
We may propose to amend § 201.413
in the future to include additional
labeling requirements for certain
specific new animal drugs as
appropriate.
1. Approved or Conditionally Approved
Corticosteroid-Containing New Animal
Drugs for Oral, Injectable, and/or
Ophthalmic Use
The proposed rule would move
labeling requirements currently
provided in § 510.410 relating to
corticosteroid-containing new animal
drugs intended for oral, injectable, and/
or ophthalmic use to proposed
§ 201.413(a). We also propose a
conforming amendment to remove
current § 510.410.
Section 510.410 was originally issued
by FDA in 1970 as § 135.101 (35 FR
11556, July 18, 1970) and provided
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background information and established
certain labeling requirements for
corticosteroid animal drugs
administered orally or parenterally. The
regulation stated that such
corticosteroid animal drugs must bear
the veterinary prescription legend and
meet the labeling requirements in
§ 201.105 for prescription new animal
drugs. The regulation also required the
labeling of these products to bear a
warning statement regarding potential
adverse reproductive effects to the
treated animals when these drugs are
administered during the last trimester of
pregnancy, specifically premature
parturition followed by dystocia, fetal
death, retained placenta, and metritis.
The regulation was subsequently
revised in 1972 (37 FR 24343, November
16, 1972) to address corticosteroid
animal drugs for oral, injectable, and
intramammary use. In 1984, FDA
amended the regulation on labeling
requirements for use of corticosteroid
animal drugs again to add ophthalmic
products, delete intramammary
products, and to include an additional
warning concerning certain potential
congenital/teratogenic effects (49 FR
48535, December 13, 1984). Ophthalmic
products were added to the regulation
based on the results of a published
study supporting the need for these
warning statements for ophthalmic use
corticosteroid drugs. Intramammary
corticosteroid animal drugs were
removed from the regulation because
intramammary products no longer
included steroids in their formulations.
The proposed rule would redesignate
§ 510.410 as proposed § 201.413(a) and
revise its contents to remove some of the
background information because we
believe it is now well understood.
Furthermore, we propose to update
some of the warning statements to use
more concise language. These animal
drug products would continue to be
subject to the labeling requirements for
prescription new animal drugs.
However, because the labeling
requirements for approved or
conditionally approved prescription
new animal drugs would no longer be
in § 201.105, we would update the
citation to refer to the labeling
requirements for prescription new
animal drugs in proposed subpart H.
The proposed rule would require the
warning statements for adverse
reproductive effects to be included in
the ‘‘Animal Safety Warnings and
Precautions’’ subsection of labeling for
approved or conditionally approved
corticosteroid new animal drugs for
oral, and/or injectable use (see proposed
§ 201.413(a)). For corticosteroid new
animal drugs approved or conditionally
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approved for ophthalmic use, per this
proposal, we may require these
statements to also be included in the
‘‘Animal Safety Warnings and
Precautions’’ subsection of labeling. For
example, the warning statements might
not be necessary for ophthalmic
corticosteroid new animal drugs if data
are provided to us that demonstrate the
intended use is not associated with
adverse reproductive effects in the
treated animal.
2. Anthelmintic New Animal Drugs
The proposed rule would move
labeling requirements currently
provided in § 500.25 for approved or
conditionally approved OTC
anthelmintic new animal drugs to
proposed § 201.413(b)(1). Labeling
requirements currently provided in
§ 500.25 for OTC anthelmintic new
animal drugs that are indexed would be
moved to § 516.155 (21 CFR 516.155),
‘‘Labeling of indexed drugs’’. We also
propose a conforming amendment to
remove current § 500.25. Furthermore,
the proposed rule would require that all
approved or conditionally approved
anthelmintic new animal drugs for use
in sheep, goats, cattle, horses, swine,
and/or poultry include statements on
labeling on appropriate use of these
drugs to minimize anthelmintic
resistance development (see proposed
§ 201.413(b)(2)).
Section 500.25 was originally issued
by FDA in 1974 as § 135.111 (39 FR
7165 at 7166, February 25, 1974) and
required that labeling for anthelmintic
animal drugs not carrying the
prescription statement bear the
following statement ‘‘Consult your
veterinarian for assistance in the
diagnosis, treatment, and control of
parasitism.’’ Labeling of approved
anthelmintic animal drugs not carrying
the prescription statement were to be
revised accordingly by February 25,
1975, and labeling of all subsequently
approved non-prescription anthelmintic
new animal drugs were to bear the
statement. In 2007, § 500.25 was
amended to add the labeling
requirement for indexed nonprescription anthelmintic new animal
drugs (72 FR 69108 at 69120, December
6, 2007).
The proposed rule would redesignate
portions of § 500.25 for approved or
conditionally approved OTC
anthelmintic new animal drugs,
including OTC anthelmintic new animal
drugs for use in animal feeds, as
proposed § 201.413(b)(1) and update
some of its contents. VFD anthelmintic
new animal drugs for use in or on
animal feeds would be excluded from
this requirement. The labeling statement
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would be required to be placed in the
‘‘Additional Recommendations’’ section
of labeling. Reference to being able to
revise labeling without prior approval
would be removed because the labeling
statement would be required for
approval or conditional approval.
Reference to an effective date of
February 25, 1975 would be removed.
Portions of § 500.25 for indexed OTC
anthelmintic new animal drugs would
be redesignated as paragraph (c) in
§ 516.155, ‘‘Labeling of indexed drugs’’.
Reference to an effective date of
February 25, 1975 would be removed.
The current § 516.155(c) would be
redesignated as § 516.155(d).
The proposed rule would also require
all approved or conditionally approved
anthelmintic new animal drugs for use
in sheep, goats, cattle, horses, swine,
and/or poultry to include statements on
their labeling providing information to
end users on appropriate use of these
drugs to minimize anthelmintic
resistance development. FDA’s Center
for Veterinary Medicine held a public
meeting on antiparasitic drug use and
resistance in ruminants and equines on
March 5 and 6, 2012. During that
meeting, a panel of veterinary
parasitology experts discussed the
emerging problem of anthelmintic
resistance cattle, horses, and especially
small ruminants in the United States,
contributing factors to resistance
development, strategies to detect and
manage anthelmintic resistance, and the
importance of educating both
veterinarians and other end users about
how to detect and manage anthelmintic
resistance. Since this meeting,
published reports in the United States
continue to support that anthelmintic
resistance is spreading and is
particularly concerning in grazing
species (cattle, sheep, goats, and horses),
but is also becoming a problem in swine
and poultry.
It is in the interest of animal health to
take a proactive approach to ensure that
anthelmintics are used appropriately to
help maintain the effectiveness of these
drugs. Therefore, the proposed rule
would require that all approved or
conditionally approved anthelmintic
new animal drugs for use in sheep,
goats, cattle, horses, swine, and/or
poultry include statements on their
labeling providing information to end
users on appropriate use of these drugs
to minimize antiparasitic resistance
development. These statements would
include information on appropriate
dosing, anthelmintic drug selection,
effectiveness monitoring, the integration
of anthelmintic drug use with other
parasite management practices, and
other information as needed (see
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proposed § 201.413(b)(2)). The
statements would be required in the
‘‘Other Warnings’’ subsection of
labeling, and if applicable, additional
statements may be required in the
‘‘Dosage and Administration’’ section of
labeling for Rx anthelmintic new animal
drugs, the ‘‘Directions’’ section of
labeling for OTC anthelmintic new
animal drugs, or the ‘‘Feeding
Directions’’ section or subsection of
labeling for anthelmintic new animal
drugs for use in animal feeds. We would
determine specific statements during
review of the new animal drug and its
labeling as part of the approval process
and/or via guidance developed by FDA.
3. Approved or Conditionally Approved
New Animal Drugs for Use in Horses
The proposed rule would require that
all approved or conditionally approved
new animal drugs for use in horses
include in the ‘‘Other Warnings’’
subsection of labeling a statement
advising against the use of the drug in
certain horses (see proposed
§ 201.413(c)). Historically, drugs
approved or conditionally approved for
use in horses do not have tolerance
levels established because FDA does not
consider horses to be food-producing
animals. Therefore, FDA currently does
not require a human food safety
evaluation of new animal drugs
intended for use in horses. Because
there is no human food safety
evaluation of the new animal drug, FDA
does not have the data needed to ensure
that horses that have been treated with
the drugs could safely be used for
human consumption and sponsors may
not label their drugs as appropriate for
use in horses intended for use as human
food. Proposed § 201.413(c) would
require that all new animal drugs
approved or conditionally approved for
use in horses include a statement in the
‘‘Other Warnings’’ subsection of labeling
advising against use of the drug in
horses intended for human
consumption.
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I. Proposed Conforming Amendments
We also propose to amend the
following sections:
• § 201.15 pertaining to foreign
translations of labeling,
• § 201.100 pertaining to prescription
drugs for human use,
• § 201.105 pertaining to prescription
drugs for animal use,
• part 501 pertaining to animal food
labeling,
• § 514.1 pertaining to new animal
drug applications, and
• § 516.155 pertaining to labeling of
indexed drugs.
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Also, we propose to remove the
following sections and incorporate their
requirements in proposed new subpart
H:
• § 500.25 pertaining to OTC
anthelmintic drug use in animals, and
• § 510.410 pertaining to
corticosteroids for oral, injectable, and
ophthalmic use in animals.
We propose to remove the following
sections:
• § 500.55 pertaining to the
exemption of certain drug-labeling
requirements, and
• §§ 510.105 and 510.106 pertaining
to labeling of drugs for use in milkproducing animals.
The proposed rule would establish
translation requirements for approved or
conditionally approved new animal
drug labeling that contains any
representation of a foreign language in
proposed § 201.404(i) and (j). Therefore,
we propose a change to § 201.15,
‘‘Drugs; prominence of required label
statements.’’ We propose adding
paragraph (4) to § 201.15(c). Proposed
paragraph (c)(4) would exempt
approved or conditionally approved
new animal drugs from the
requirements established in § 201.15(c)
and state that foreign translations of the
labeling for approved or conditionally
approved new animal drugs must
comply with § 201.404(i) and (j).
The proposed rule would amend
§ 201.100, ‘‘Prescription drugs for
human use,’’ in paragraph (d) to remove
the words, ‘‘and § 201.105(b)(2)’’ from
the introductory text. This conforming
amendment would be in conjunction
with conforming amendments proposed
for § 201.105, ‘‘Veterinary drugs’’ (see
discussion below), which includes the
removal of § 201.105(f). Paragraph (f)
provides labeling requirements for
prescription drugs intended for both
human and veterinary use.
Current § 201.105, entitled
‘‘Veterinary drugs,’’ provides
requirements, including labeling
requirements, for drugs subject to
section 503(f)(1) of the FD&C Act, which
are prescription drugs for animal use.
These drugs include approved or
conditionally approved prescription
new animal drugs, prescription new
animal drugs listed in the index of
legally marketed unapproved new
animal drugs for minor species, and
prescription animal drugs not subject to
an approved or conditionally approved
application or index listing. Section
201.100, ‘‘Prescription drugs for human
use,’’ serves a similar purpose for
prescription human drugs. The
proposed rule would revise the title of
§ 201.105 to read ‘‘Prescription drugs for
animal use.’’ This would clarify the
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18309
scope of the section and be consistent
with the title of its counterpart for
human prescription drugs in § 201.100.
We propose minor editorial changes
to update § 201.105(a), which provides
requirements, other than labeling
requirements, for prescription animal
drugs.
To accommodate the proposed
content and format requirements in
proposed subpart H for labeling
authorized in approved or conditionally
approved new animal drug applications,
the proposed rule would change
§ 201.105 to provide the labeling
requirements for approved or
conditionally approved prescription
new animal drugs separately from the
labeling requirements for prescription
new animal drugs listed in the index of
legally marketed unapproved new
animal drugs for minor species, and
prescription animal drugs not subject to
an approved or conditionally approved
application or index listing.
Accordingly, we propose to insert a new
paragraph § 201.105(b) that would
provide labeling requirements for
prescription new animal drugs
approved under section 512 of the FD&C
Act or conditionally approved under
section 571 of the FD&C Act. The
provisions in the proposed paragraph
§ 201.105(c) would apply to prescription
new animal drugs listed in the index of
legally marketed unapproved new
animal drugs for minor species
established under section 572 of the
FD&C Act, and prescription animal
drugs not subject to an approved or
conditionally approved application or
index listing.
The proposed rule would provide
requirements for the labeling
components for approved or
conditionally approved prescription
new animal drugs identified in
proposed § 201.405 (see proposed
§ 201.105(b)(1)), which include labeling
providing full prescribing information,
labels, small labels, labeling for
secondary containers that include a
package insert, shipping labeling, and
other approved labeling for prescription
new animal drugs. Such labeling would
be required to contain adequate
information for use of the drug,
including indications for use, dosages,
routes of administration, frequency and
duration of administration, and any
relevant contraindications, warnings,
precautions, and adverse reactions,
under which veterinarians licensed by
law to administer the drug can use the
drug safely and for the purposes for
which it is intended, including all
purposes for which it is advertised or
represented (see proposed
§ 201.105(b)(1)(i)). The labeling
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components identified in proposed
§ 201.405 also would be required to be
the labeling authorized by the approved
new animal drug application or
conditionally approved new animal
drug application for the prescription
new animal drug (see proposed
§ 201.105(b)(1)(ii)).
These requirements for the labeling
components identified in proposed
§ 201.405 would be consistent with
requirements in current paragraph
§ 201.105(c) for labeling on or within
the package from which the approved or
conditionally approved prescription
new animal drugs is dispensed. We also
propose editorial revisions to use more
current terminology regarding the types
of information required to provide
adequate information for use of the drug
by veterinarians. These labeling
components also would be required to
comply with the applicable content and
format requirements of proposed
subpart H (see proposed
§ 201.105(b)(1)(iii)).
The exemption currently provided in
§ 201.105(c)(2) permits, upon written
request to the Commissioner of Food
and Drugs, the labeling information
required by § 201.105(c)(1) (i.e.,
adequate information for use) to be
omitted from the dispensing container
of prescription animal drugs for which
the directions, hazards, warnings, and
use information are commonly known
to licensed veterinarians. Providing an
exemption from the requirement that all
prescription animal drugs must provide
labeling that bears adequate information
for use by veterinarians does not ensure
safe and effective use of these drugs and
is no longer warranted. Additional risks
relating to the use of an animal drug
may become known long after the drug
is first marketed, even when
veterinarians have become familiar with
the directions, hazards, and warnings
concerning its use. Moreover, in some
cases, labeling may need to be revised
to include additional safety information.
Therefore, the proposed rule would
revoke the exemption provided in
current § 201.105(c)(2). As discussed
below, we also propose to remove
§ 500.55, which lists the animal drugs to
which this exemption has been applied.
The proposed rule would set forth
requirements for any labeling, as
defined in section 201(m) of the FD&C
Act, for approved or conditionally
approved prescription new animal
drugs, distributed by or on behalf of the
manufacturer, packer, or distributor of
the drug, that provides or purports to
provide information for use or
prescribes, recommends, or suggests a
dosage for use of the drug (see proposed
§ 201.105(b)(2)), consistent with the
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requirements in current § 201.105(d) for
such prescription new animal drugs.
Labeling, as defined in section 201(m) of
the FD&C Act, means ‘‘all labels and
other written, printed, or graphic matter
(1) upon any article or any of its
containers or wrappers, or (2)
accompanying such article.’’ Thus,
labeling includes material such as
promotional labeling, in addition to the
labeling authorized in the approved new
animal drug application or the
conditionally approved new animal
drug application. Such labeling that
provides or purports to provide
information or a dosage for the drug’s
use would be required to contain
adequate information to ensure licensed
veterinarians can use the drug safely
and for the purposes for which the drug
is intended, including all conditions for
which the drug is advertised or
represented. For the labeling of the
approved or conditionally approved
prescription animal drug to contain
adequate information for use by
veterinarians, proposed § 201.105(b)(2)
would require such labeling to include
the indications for use, dosages, routes
of administration, frequency and
duration of administration, and any
relevant contraindications, warnings,
precautions, and adverse reactions, and
information relevant to compliance with
the new animal drug provisions of the
FD&C Act. It would also require the
labeling components providing such
information for use to be the same in
language and emphasis as the labeling
authorized by the approved or
conditionally approved new animal
drug application, and any other labeling
components would have to be
consistent with and not contrary to such
authorized labeling (see proposed
§ 201.105(b)(2)(i)). The labeling would
be required to contain the same
information concerning the ingredients
of the drug as appears on the labeling
authorized by the approved new animal
drug application or the conditionally
approved new animal drug application
(see proposed § 201.105(b)(2)(ii)).
We propose requirements for the label
of prescription new animal drugs listed
in the index of legally marketed
unapproved new animal drugs for minor
species established under section 572 of
the FD&C Act, and prescription animal
drugs not subject to an approved or
conditionally approved application or
index listing, that are consistent with
those currently provided in § 201.105(b)
(see proposed § 201.105(c)(1)). The
proposed rule includes requirements for
the labeling on or within the package
from which such drugs are to be
dispensed that are consistent with the
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requirements currently provided in
§ 201.105(c) (see proposed
§ 201.105(c)(2)). In addition, the
proposed rule includes editorial
revisions to use more current
terminology to identify the types of
information that would need to be
included on the labeling on or within
the dispensing container in order to
provide adequate information for use of
such drugs by veterinarians (see
proposed § 201.105(c)(2)). The proposed
rule would revoke the exemption
provided in current § 201.105(c)(2) for
the reasons described previously.
Proposed § 201.105(c)(3) would
require that any labeling, as defined in
section 201(m) of the FD&C Act, for
prescription new animal drugs listed in
the index of legally marketed
unapproved new animal drugs for minor
species, or prescription animal drugs
not subject to an approved or
conditionally approved application or
an index listing, that is distributed by or
on behalf of the manufacturer, packer,
or distributor of the drug, that provides
information for use or a dosage for use
of the drug contain adequate
information for use of the drug by
licensed veterinarians. This provision is
consistent with the requirements
currently provided in § 201.105(d) for
these prescription animal drugs. In
addition, all labeling for such
prescription animal drugs, except labels
and cartons, that contain information for
use of the drug would be required to
include the date of the issuance or latest
revision of such labeling, consistent
with the requirements currently
provided in § 201.105(e) (see proposed
§ 201.105(c)(4)).
The proposed rule would replace the
current proviso language in
§ 201.105(d)(2) relating to prescription
animal drug reminder-piece labeling
with a provision that is similar to the
reminder labeling provision at
§ 201.100(f) (21 CFR 201.100(f)) for
human prescription drugs (see proposed
§ 201.105(d)). Specifically, the proposed
provision would replace the term
reminder-piece labeling with the term
reminder labeling and define reminder
labeling for prescription animal drugs in
a manner similar to how that term is
defined for prescription human drugs.
In the past, we have relied on the
definition for reminder labeling in
§ 201.100(f) as a guide when reviewing
such labeling because the current
proviso language in § 201.105 lacks such
a detailed definition. We propose to
modify the definition for reminder
labeling found at § 201.100(f) to
establish a similar definition for
prescription animal drugs. The
proposed use of the term reminder
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labeling for prescription animal drugs
and the proposed inclusion of a
definition for this term that is similar to
the definition in § 201.100(f) is clearer
and more accurate than the current
definition for reminder-piece labeling
(see proposed § 201.105(d)).
Current § 201.105(f) provides labeling
requirements for prescription drugs
intended for both human and veterinary
use. The proposed rule would remove
this provision, which was established in
1960 (as § 1.106(c)(6)); 25 FR 12592) and
is now obsolete. In 1968, section 512 of
the FD&C Act established separate
approval requirements for new animal
drugs, including their labeling.
The proposed rule would remove
§ 500.25, which contains labeling
requirements for OTC anthelmintic new
animal drugs. The requirements for the
labeling of approved or conditionally
approved OTC anthelminthic new
animal drugs contained in current
§ 500.25 would be moved to proposed
§ 201.413(b)(1), ‘‘Labeling requirements
for certain approved or conditionally
approved new animal drugs.’’ This
would further consolidate regulations
pertaining to labeling of approved or
conditionally approved new animal
drugs. The requirements for the labeling
of indexed OTC anthelminthic new
animal drugs contained in current
§ 500.25 would be moved to § 516.155,
‘‘Labeling of indexed drugs.’’
To ensure the safe and effective use of
new animal drugs, the proposed rule
would remove from the provision found
at § 500.55, ‘‘Exemption from certain
drug-labeling requirements,’’ and
proviso language at § 201.105(c)(2) that
permits animal drug sponsors to receive
an exemption from including certain
labeling information required by
§ 201.105(c)(1) on the dispensing
package for their products where the
Commissioner of Food and Drugs has
determined that such information is
already commonly known to
veterinarians. Under § 201.105(c)(1) of
this Agency’s regulations, the labeling
on or within the dispensing package of
prescription new animal drugs must
have adequate information for its use,
including indications, effects, dosages,
routes, methods, and frequency and
duration of administration, and any
relevant hazards, contraindications, side
effects, and precautions, under which
veterinarians licensed by law to
administer the drug can use it safely and
for the purposes for which the drug is
intended, including all purposes for
which the drug is advertised or
represented. Section 201.105(c)(2)
contains certain proviso language that
permits the ‘‘full disclosure’’ labeling
required by § 201.105(c)(1) to be omitted
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from the dispensing package of
prescription new animal drugs if the
directions, hazards, warnings, and use
information are commonly known to
veterinarians. The Commissioner of
Food and Drugs has, upon written
request, offered an opinion that such
information may be omitted from the
dispensing package for the prescription
animal drugs listed in § 500.55. Only
eight animal drugs have received such
an exemption from providing the full
disclosure labeling information
otherwise required by § 201.105(c)(1).
The list of unapproved prescription
animal drugs currently in § 500.55 that
have received an exemption from
providing full disclosure labeling
meeting the requirements of
§ 201.105(c)(1) on their dispensing
package was initially created in 1962.
This list was added to a then-existing
provision at 21 CFR 3.515 that
permitted full disclosure labeling to be
omitted from the dispensing package of
certain prescription drugs for human
use in cases where the Commissioner of
Food and Drugs determined that
directions, hazards, warnings, and use
information for such drugs was
commonly known to physicians (27 FR
5428, June 8, 1962). In 1971, when FDA
issued regulations implementing the
Animal Drug Amendments of 1968, the
human and animal drug provisions were
recodified in separate sections of FDA’s
regulations. As a result, the list of
animal drugs exempt from the
requirement to have full disclosure
labeling on their dispensing package
was moved to § 135.107 and the list of
human prescription drugs exempt from
similar labeling requirements was
moved to § 201.160. In the mid-1970s,
as part of the Agency’s reorganization of
its regulations, the animal drug list was
moved again to § 500.55.
In 1979, FDA removed § 201.160, the
human drug provision similar to
§ 500.55, because the Agency’s
experience had shown that risks from
the use of a drug may be uncovered long
after the drug is first marketed, even for
long-used drugs for which physicians
had become familiar with the directions,
hazards, and warnings concerning their
use. FDA concluded that current full
disclosure labeling should be provided
for all human prescription drugs to
ensure that physicians have the
information they need to use these
drugs safely. For similar reasons, full
disclosure labeling is needed for all
prescription new animal drugs to ensure
veterinarians are able to use these
products safely and effectively. In
addition, none of the eight products
listed in § 500.55 received FDA
approval for the uses in animals for
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18311
which they were generally employed by
veterinarians at the time the list of
exempt drugs was initially established
in 1962, and several are no longer used
in veterinary medicine. Therefore, we
propose to remove § 500.55 and the
proviso language at § 201.105(c)(2).
In part 501 subpart A, we propose to
add a new section, § 501.19, ‘‘Animal
food; labeling of animal food containing
new animal drugs.’’ Proposed § 501.19
would require labeling of animal food
containing an approved or conditionally
approved new animal drug to comply
with proposed § 201.409. The
requirements in part 501 would apply
only as specified in proposed § 201.409.
The proposed rule would remove
§ 510.105, ‘‘Labeling of drugs for use in
milk-producing animals’’, and
§ 510.106, ‘‘Labeling of antibiotic and
antibiotic-containing drugs intended for
use in milk-producing animals’’, which
provide statements required to appear
on the labeling of such drugs for use in
milk-producing animals. The
requirements in proposed
§ § 201.405(a)(10)(i), 201.407(a)(7)(i),
and 201.409(a)(10)(i) would supersede
the requirements in §§ 510.105 and
510.106.
Section 510.105 was originally issued
by FDA in 1960 as 21 CFR 3.18 (25 FR
8321, August 31, 1960) and was
recodified as § 135.103 (21 CFR 135.103)
in 1971 (36 FR 18375 at 18393,
September 14, 1971). In 1975 § 135.103
was redesignated as § 510.105 (40 FR
13802, March 27, 1975).
Section 510.106 was originally issued
by FDA in 1960 as § 146.14 (21 CFR
146.14) (25 FR 8321 at 8322, August 31,
1960). In 1964, § 146.14 was
redesignated as § 148.5 (21 CFR 148.5)
(29 FR 15672, November 21, 1964) and
subsequently amended in 1965 (30 FR
7040 at 7041, May 26, 1965) to update
the warning statements. In 1975 § 148.5
was redesignated as § 510.106 (40 FR
13802, March 27, 1975).
Both §§ 510.105 and 510.106 were
amended in 1998 to update the warning
statements in those provisions to reflect
current practices in the dairy industry
(63 FR 32978, June 17, 1998).
The proposed rule would remove
§§ 510.105 and 510.106 because the
labeling requirements proposed for the
subsection entitled ‘‘Withdrawal
Periods and Residue Warnings’’ or
‘‘Withdrawal Periods’’ would supersede
such requirements in §§ 510.105 and
510.106. The labeling requirements for
the proposed ‘‘Withdrawal Periods and
Residue Warnings’’ or ‘‘Withdrawal
Periods’’ subsection would provide
flexibility to have more targeted and
informative statements with respect to
human food safety warnings, including
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milk discard times, withdrawal periods,
and residue warning statements for the
labeling of all new animal drugs
intended for use in food-producing
animals (see proposed
§ § 201.405(a)(10)(i), 201.407(a)(7)(i),
and 201.409(a)(10)(i)).
The proposed rule would remove
§ 510.410. The requirements in current
§ 510.410 would be moved to proposed
§ 201.413, ‘‘Labeling requirements for
certain approved or conditionally
approved new animal drugs.’’ The
warning language would be clarified
and updated in proposed § 201.413(a).
This would further consolidate
regulations pertaining to labeling of
approved or conditionally approved
new animal drugs.
The proposed rule would amend
§ 514.1, which describes the
requirements for applications for new
animal drugs. Current § 514.1(b)(3)
describes the labeling that must be
included in a new animal drug
application. Paragraphs (ii) through (vi)
of current § 514.1(b)(3) describe the
labeling required in a new animal drug
application for prescription and
nonprescription new animal drugs and
new animal drugs intended for use in
the manufacture of medicated feeds.
The proposed rule would insert a
paragraph after § 514.1(b)(3)(i) to
indicate that the content and format of
all proposed labeling must comply with
subpart H of part 201 of this chapter.
Paragraphs (ii) through (vi) of
§ 514.1(b)(3) would be redesignated as
paragraphs (iii) through (vii). The
current text ‘‘prescription veterinary
drugs’’ in redesignated paragraphs (iv)
and (vii) would be changed to
‘‘prescription new animal drugs’’ to be
consistent with the text used in
proposed subpart H.
VI. Proposed Effective/Compliance
Dates
If finalized, sponsors of new animal
drugs would need to comply with these
proposed regulations within 6 years of
the effective date of the final rule,
according to the compliance schedule
provided in the General Requirements
section of this proposed rule, discussed
in section V.C. The compliance
schedule is based on application
number, with approved NADAs with
higher application numbers having the
earliest compliance date because they
are more recently approved and
therefore likely to need the fewest
labeling revisions. The 6-year
compliance period would begin on the
effective date of the final rule (see
proposed § 201.404(a)(4)).
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VII. Preliminary Economic Analysis of
Impacts
We have examined the impacts of the
proposed rule under Executive Order
12866, Executive Order 13563,
Executive Order 14094, the Regulatory
Flexibility Act (5 U.S.C. 601–612), and
the Unfunded Mandates Reform Act of
1995 (Pub. L. 104–4).
Executive Orders 12866, 13563, and
14094 direct us to assess all benefits,
costs, and transfers of available
regulatory alternatives and, when
regulation is necessary, to select
regulatory approaches that maximize
net benefits (including potential
economic, environmental, public health
and safety, and other advantages;
distributive impacts; and equity). Rules
are ‘‘significant’’ under Executive Order
12866 Section 3(f)(1) (as amended by
Executive Order 14094) if they ‘‘have an
annual effect on the economy of $200
million or more (adjusted every 3 years
by the Administrator of [the Office of
Information and Regulatory Affairs
(OIRA)] for changes in gross domestic
product); or adversely affect in a
material way the economy, a sector of
the economy, productivity, competition,
jobs, the environment, public health or
safety, or State, local, territorial, or tribal
governments or communities.’’ OIRA
has determined that this proposed rule
is not a significant regulatory action as
defined by Executive Order 12866
Section 3(f)(1).
The Regulatory Flexibility Act
requires us to analyze regulatory options
that would minimize any significant
impact of a rule on small entities.
Because net annualized compliance
costs of the proposed rule are less than
2 percent of average annual revenues for
the smallest firms in the industry, we
propose to certify that the proposed rule
will not have a significant economic
impact on a substantial number of small
entities.
The Unfunded Mandates Reform Act
of 1995 (section 202(a)) requires us to
prepare a written statement, which
includes an assessment of anticipated
impacts, before proposing ‘‘any rule that
includes any Federal mandate that may
result in the expenditure by State, local,
and tribal governments, in the aggregate,
or by the private sector, of $100,000,000
or more (adjusted annually for inflation)
in any one year.’’ The current threshold
after adjustment for inflation is $177
million, using the most current (2022)
Implicit Price Deflator for the Gross
Domestic Product. This proposed rule
would not result in an expenditure in
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any year that meets or exceeds this
amount.
The proposed rule, if finalized, would
require that sponsors follow specific
content and format requirements for
labeling of approved or conditionally
approved new animal drugs. A
comprehensive set of standardized
requirements for the content and format
of information on labeling of such drugs
currently does not exist. Veterinarians,
pet owners, livestock owners, and other
users of new animal drugs may more
easily locate the information they need
with standardized labeling.
We quantify potential cost savings to
industry and FDA from a reduction in
the quantity and time burden of new
animal drug labeling amendments and
informal communications related to
new animal drug labeling. There may be
additional benefits to users of approved
or conditionally approved new animal
drugs from greater predictability and
ease of reading new animal drug
labeling in the form of time saved
searching for content, which we are
unable to quantify. Additionally, animal
or human health benefits may result
from reductions in medication errors or
improvements in adverse event
reporting, which we cannot quantify.
We expect that new animal drug
sponsors would incur one-time costs to
read and understand the rule, revise
standard operating procedures (SOPs)
related to labeling, and train employees
on the revised SOPs. New animal drug
sponsors would also bear costs to
update labeling and prepare
supplemental labeling applications to
conform to the proposed requirements.
FDA would incur costs to review these
supplemental applications.
We summarize the quantified benefits
and costs in table 2. We estimate that
the annualized benefits over 10 years
would range from $0.143 million to
$0.243 million at a 2 percent discount
rate, with a primary estimate of $0.193
million. The annualized costs would
range from $2.16 million to $2.77
million at a 2 percent discount rate,
with a primary estimate of $2.45
million.
The present value of total benefits
over 10 years would range from $1.31
million to $2.23 million at a 2 percent
discount rate, with a primary estimate of
$1.77 million. At a 2 percent discount
rate, the present value of total costs
would range from $19.78 million to
$25.38 million, with a primary estimate
of $22.48 million.
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18313
TABLE 2—SUMMARY OF BENEFITS, COSTS, AND DISTRIBUTIONAL EFFECTS OF THE PROPOSED RULE
[Millions of 2022 dollars]
Primary
estimate
Category
Benefits:
Annualized monetized benefits ............................
Annualized quantified, but non-monetized, benefits.
Unquantified benefits ...........................................
COSTS:
Annualized monetized costs ................................
Annualized quantified, but non-monetized, costs
Unquantified costs ...............................................
Transfers:
Annualized monetized Federal budgetary transfers.
Bearers of transfer gain and loss? ......................
Other annualized monetized transfers ................
Bearers of transfer gain and loss? ......................
Net Benefits:
Annualized monetized net benefits .....................
High
estimate
2022
2
10
..................
..................
..................
..................
..................
..................
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Cost savings to industry and
FDA.
Information search cost savings to users of new animal drugs and potential
benefits to animal or human health.
2.45
..................
..................
2.16
..................
..................
2.77
..................
..................
2022
..................
..................
2
..................
..................
10
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
..................
¥2.02
¥2.53
2022
2
¥2.26
None.
Quantified effects of less than 2 percent of average annual revenues for
the smallest firms.
None.
None.
IX. Paperwork Reduction Act of 1995
This proposed rule contains
information collection provisions that
are subject to review by the OMB under
the Paperwork Reduction Act of 1995
(44 U.S.C. 3501–3521). A description of
these provisions is given in the
Description section of this document
with an estimate of the annual reporting
Time
horizon
$0.243
Effects on State, local, or Tribal governments ...........
Effects on small businesses .......................................
VIII. Analysis of Environmental Impact
The Agency has determined under
§ 25.30(k) that this action is of a type
that does not individually or
cumulatively have a significant effect on
the human environment. Therefore,
neither an environmental assessment
nor an environmental impact statement
is required.
Discount
rate
$0.143
Effects
We have developed a comprehensive
Preliminary Economic Analysis of
Impacts that assesses the impacts of the
proposed rule. The full preliminary
analysis of economic impacts is
available in the docket for this proposed
rule (Ref. 2) and at https://www.fda.gov/
about-fda/economics-staff/regulatoryimpact-analyses-ria.
Dollar
year
$0.193
Category
Effects on wages ........................................................
Effects on growth ........................................................
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Low
estimate
Notes (e.g., Risk
assumptions; source
citations; whether inclusion
of capital effects differs
across low, primary, high
estimates; etc.)
burden. Included in the estimate is the
time for reviewing instructions,
searching existing data sources,
gathering and maintaining the data
needed, and completing and reviewing
each collection of information.
FDA invites comments on these
topics: (1) whether the proposed
collection of information is necessary
for the proper performance of FDA’s
functions, including whether the
information will have practical utility;
(2) the accuracy of FDA’s estimate of the
burden of the proposed collection of
information, including the validity of
the methodology and assumptions used;
(3) ways to enhance the quality, utility,
and clarity of the information to be
collected; and (4) ways to minimize the
burden of the collection of information
on respondents, including through the
use of automated collection techniques,
when appropriate, and other forms of
information technology.
Title: Reporting Associated With New
Animal Drug Applications and
Veterinary Master Files; OMB control
number 0910–0032—Revision.
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10
Notes
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Description: The proposed rule, if
finalized, would revise the existing
requirements for the content and format
of labeling for approved or conditionally
approved new animal drugs that
sponsors submit as part of NADAs or
CNADAs, respectively. The proposed
rule would also place labeling
requirements that are specific to
approved or conditionally approved
new animal drugs in a single location in
the CFR. The proposed rule would
apply to the labeling of both Rx and
OTC new animal drugs, as well as new
animal drugs for use in animal feeds.
The proposed regulations would
provide the following for the content
and format elements of labeling for
approved or conditionally approved
new animal drugs:
Description of Respondents:
Respondents include persons
developing, manufacturing, and/or
researching new animal drugs,
commonly referred to as new animal
drug sponsors.
We estimate the burden of the
information collection as follows:
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Federal Register / Vol. 89, No. 49 / Tuesday, March 12, 2024 / Proposed Rules
TABLE 3—ESTIMATED ONE-TIME REPORTING BURDEN
21 CFR section; activity
Number of
respondents
Number of
responses per
respondent
Total
responses
Average
burden per
response
Total hours
514.8 and 514.8(c)(2); supplements and changes to an
approved application ........................................................
66
1 12.55
2 828
20
16,560
1 Decimal
rounded up.
2 Decimal rounded down.
To ease the burden of the information
collection on respondents, we have
established a 6-year implementation
period. We estimate 828 supplemental
labeling applications of approved and
marketed new animal drugs over the
course of 6 years to comply with the
labeling regulations, if finalized. Based
an application for an approved and
marketed new animal drug, for an
average of 12.55 submissions per
respondent. We further assume it takes
an average of 20 hours to prepare each
submission for a total of 16,560 hours.
on internal data, there were 78 unique
firms with an approved or conditionally
approved new animal drug application
(sponsors) in September 2023. Sixty-six
of these sponsors currently had an
approved and marketed new animal
drug. We assume 828 submissions
regarding supplements and changes to
TABLE 4—ESTIMATED ONE-TIME RECORDKEEPING BURDEN
Number of
Recordkeepers
Activity
Total
annual
records
Average
burden per
recordkeeping
Total hours
Reading and understanding the rule .................................
Writing new labeling SOPs ................................................
Training ..............................................................................
156
156
156
1
1
1
156
156
156
6
2.14
0.89
1 334
Total ............................................................................
..........................
........................
........................
........................
1,409
1 Decimal
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Number of
records per
recordkeeper
936
1 139
rounded up.
We estimate that approved new
animal drug sponsors will incur onetime burden attributable to reading and
understanding the rule, revising SOPs
related to labeling, and training
employees on the revised SOPs. We
estimate the average time to read and
understand the proposed rule is 6 hours
(156 × 6 = 936 hours). We estimate that
small businesses will spend 4 hours and
large business will spend 8 hours
revising SOPs related to labeling. Based
on data from the 2017 Statistics of U.S.
Businesses, there are 72 small business
entities and 6 large business entities.
((72 × 4) + (6 × 8) ÷ 156 = 2.14 hours
per record). We also estimate that small
businesses will spend 1 hour and large
businesses will spend 12 hours to train
employees on the revised SOPs ((72 × 1)
+ (6 × 12) ÷ 156 = 0.89 hours per record).
We assume at least two recordkeepers
per drug sponsor.
To ensure that comments on
information collection are received,
OMB recommends that written
comments be submitted through
reginfo.gov (see ADDRESSES). All
comments should be identified with the
title of the information collection.
In compliance with the Paperwork
Reduction Act of 1995 (44 U.S.C.
3407(d)), we have submitted the
information collection provisions of this
proposed rule to OMB for review. These
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information collection requirements
will not be effective until FDA
publishes a final rule, OMB approves
the information collection requirements,
and the rule goes into effect. FDA will
announce OMB approval of these
requirements in the Federal Register.
X. Federalism
We have analyzed this proposed rule
in accordance with the principles set
forth in Executive Order 13132:
Federalism. The Order requires Federal
Agencies to examine actions carefully to
determine if they contain policies that
have federalism implications or that
preempt State law. As defined in the
Order, ‘‘policies that have federalism
implications’’ refers to regulations,
legislative comments or proposed
legislation, and other policy statements
or actions that have substantial direct
effects on the States, on the relationship
between the Federal Government and
the States, or on the distribution of
power and responsibilities among the
various levels of government.
Section 4(a) of the Order requires
Agencies to ‘‘construe . . . a Federal
statute to preempt State law only where
the statute contains an express
preemption provision or there is some
other clear evidence that the Congress
intended preemption of State law, or
where the exercise of State authority
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conflicts with the exercise of Federal
authority under the Federal statute.’’
The sole statutory provision giving
preemptive effect to this proposed rule
is section 751 of the FD&C Act (21
U.S.C. 379r), which would apply only
with respect to nonprescription animal
drugs. There are no express preemption
provisions of the FD&C Act applicable
to prescription animal drugs.
We have complied with all of the
applicable requirements under the
Executive order and have determined
that the preemptive effect of this
proposed rule, if finalized, would be
consistent with Executive Order 13132.
Through publication of this proposed
rule, we are providing notice and an
opportunity for State and local officials
to comment on this rulemaking.
XI. Consultation and Coordination With
Indian Tribal Governments
We have analyzed this proposed rule
in accordance with the principles set
forth in Executive Order 13175. We
have tentatively determined that the
rule does not contain policies that
would have a substantial direct effect on
one or more Indian Tribes, on the
relationship between the Federal
Government and Indian Tribes, or on
the distribution of power and
responsibilities between the Federal
Government and Indian Tribes. The
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Agency solicits comments from tribal
officials on any potential impact on
Indian Tribes from this proposed action.
XII. References
The following references are on
display in the Dockets Management
Staff (see ADDRESSES) and are available
for viewing by interested persons
between 9 a.m. and 4 p.m. Monday
through Friday; they are also available
electronically at https://
www.regulations.gov. Although FDA has
verified the website addresses in this
document, please note that websites are
subject to change over time.
1. FDA, Preliminary Regulatory Impact,
Initial Regulatory Flexibility, and
Unfunded Mandates Reform Act
Analyses, 2023; Docket No. FDA–2023–
N–5160; https://www.fda.gov/about-fda/
economics-staff/regulatory-impactanalyses-ria.
List of Subjects
21 CFR Part 201
Drugs, Labeling, Reporting and
Recordkeeping requirements.
21 CFR Part 500
Animal drugs, Animal feeds, Cancer,
Labeling, Packaging and containers,
Polychlorinated biphenyls (PCB’s).
21 CFR Part 501
Animal foods, Packaging and
containers, Reporting and recordkeeping
requirements.
21 CFR Part 510
Administrative practice and
procedure, Animal drugs, Labeling,
Reporting and recordkeeping
requirements.
21 CFR Parts 514 and 516
Administrative practice and
procedure, Animal drugs, Confidential
business information, Reporting and
recordkeeping requirements.
Therefore, under the Federal Food,
Drug, and Cosmetic Act and under
authority delegated to the Commissioner
of Food and Drugs, we propose that 21
CFR parts 201, 500, 501, 510, 514, and
516 be amended as follows:
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PART 201—LABELING
1. The authority citation for part 201
is revised to read as follows:
■
Authority: 21 U.S.C. 321, 331, 343, 351,
352, 353, 354, 355, 358, 360, 360b, 360ccc,
360ccc–1, 360ee, 360gg–360ss, 371, 374,
379e; 42 U.S.C. 216, 241, 262, 264.
2. In § 201.15, add paragraph (c)(4) to
read as follows:
■
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§ 201.15 Drugs; prominence of required
label statements.
*
*
*
*
*
(c) * * *
(4) Approved or conditionally
approved new animal drugs are
exempted from the requirements in
paragraph (c). Foreign language
translations of the labeling for approved
or conditionally approved new animal
drugs must comply with § 201.404(i)
and (j).
§ 201.100
[Amended].
3. In § 201.100, in paragraph (d)
introductory text remove the words,
‘‘and § 201.105(b)(2)’’.
■ 4. Revise § 201.105 to read as follows:
■
§ 201.105
use.
Prescription drugs for animal
A drug subject to the requirements of
section 503(f)(1) of the Federal Food,
Drug, and Cosmetic Act is exempt from
section 502(f)(1) of the Federal Food,
Drug, and Cosmetic Act if all the
following conditions are met:
(a) The prescription animal drug is:
(1)(i) In the possession of a person, or
the person’s agents or employees,
regularly and lawfully engaged in the
manufacture, transportation, storage, or
wholesale distribution of drugs that are
to be used only by or on the prescription
or other order of a licensed veterinarian;
or
(ii) In the possession of a retail,
hospital, or clinic pharmacy, or other
person authorized under State law to
dispense prescription animal drugs,
who is regularly and lawfully engaged
in dispensing drugs that are to be used
only by or on the prescription or other
order of a licensed veterinarian; or
(iii) In the possession of a licensed
veterinarian for use in the course of his
or her professional practice; and
(2) To be dispensed in accordance
with section 503(f) of the Federal Food,
Drug, and Cosmetic Act.
(b) For prescription new animal drugs
approved under section 512 of the
Federal Food, Drug, and Cosmetic Act
or conditionally approved under section
571 of the Federal Food, Drug, and
Cosmetic Act:
(1) The labeling components
identified in § 201.405 for the
prescription new animal drug:
(i) Contain adequate information for
its use, including indications for use,
dosages, routes of administration,
frequency and duration of
administration, and any relevant
contraindications, warnings,
precautions, and adverse reactions,
under which veterinarians licensed by
law to administer the drug can use the
drug safely and for the purposes for
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18315
which it is intended, including all
purposes for which it is advertised or
represented;
(ii) Are authorized by the approved
new animal drug application or the
conditionally approved new animal
drug application for the prescription
new animal drug; and
(iii) Comply with the applicable
content and format requirements of
subpart H of this part.
(2) Any labeling, as defined in section
201(m) of the Federal Food, Drug, and
Cosmetic Act, for the approved or
conditionally approved prescription
new animal drug, distributed by or on
behalf of the manufacturer, packer, or
distributor of the drug, that provides or
purports to provide information for its
use or a dosage for its use contains:
(i) Adequate information for such use,
including indications for use, dosages,
routes of administration, frequency and
duration of administration, and any
relevant contraindications, warnings,
precautions, and adverse reactions, and
information relevant to compliance with
the new animal drug provisions of the
Federal Food, Drug, and Cosmetic Act,
under which veterinarians licensed by
law to administer the drug can use the
drug safely and for the purposes for
which it is intended, including all
conditions for which it is advertised or
represented, and the labeling
components providing such information
for use are the same in language and
emphasis as labeling authorized by the
approved new animal drug application
or the conditionally approved new
animal drug application, and any other
labeling components are consistent with
and not contrary to such authorized
labeling; and
(ii) The same information concerning
the ingredients of the drug as appears on
the labeling authorized by the approved
new animal drug application or the
conditionally approved new animal
drug application.
(c) For prescription new animal drugs
listed in the index of legally marketed
unapproved new animal drugs for minor
species established under section 572 of
the Federal Food, Drug, and Cosmetic
Act, or prescription animal drugs not
subject to an approved or conditionally
approved application or indexed listing:
(1) The label of the drug bears:
(i) The statement, ‘‘Caution: Federal
law restricts this drug to use by or on
the order of a licensed veterinarian’’;
(ii) The recommended or usual
dosage;
(iii) The route of administration, if it
is not for oral use;
(iv) The quantity or proportion of
each active ingredient as well as the
information required by section 502(e)
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of the Federal Food, Drug, and Cosmetic
Act; and
(v) If it is for other than oral use, the
names of all inactive ingredients, except
that:
(A) Flavorings and perfumes may be
designated as such without naming their
components;
(B) Color additives may be designated
as coloring without naming specific
color components unless the naming of
such components is required by a color
additive regulation prescribed in
subchapter A of this chapter; and
(C) Trace amounts of harmless
substances added solely for individual
product identification need not be
named.
(vi) If it is intended for administration
by parenteral injection, the quantity or
proportion of all inactive ingredients,
except that ingredients added to adjust
the pH or to make the drug isotonic may
be declared by name and a statement of
their effect; and if the vehicle is water
for injection, it need not be named.
(vii) An identifying lot or control
number from which it is possible to
determine the complete manufacturing
history of the package of the drug.
(viii) In the case of containers too
small or otherwise unable to
accommodate a label with sufficient
space to bear all of the information
required by paragraph (c)(1) of this
section, but which are packaged within
an outer container from which they are
removed for dispensing or use, the
information required by paragraphs
(c)(1)(ii), (iii), (v), and (vi) of this section
may be contained in other labeling on
or within the package from which the
drug is to be so dispensed, and the
information referred to in paragraph
(c)(1)(i) of this section may be placed on
such outer container only, and the
information required by paragraph
(c)(1)(vii) of this section may be placed
on the crimp of the dispensing tube.
(2) The labeling on or within the
package from which the drug is to be
dispensed:
(i) Bears adequate information for its
use, including indications for use,
dosages, routes of administration,
frequency and duration of
administration, and any relevant
contraindications, warnings,
precautions, and adverse reactions,
under which veterinarians licensed by
law to administer the drug can use the
drug safely and for the purposes for
which it is intended, including all
purposes for which it is advertised or
represented; and
(ii) For prescription new animal drugs
listed in the index of legally marketed
unapproved new animal drugs for minor
species established under section 572 of
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the Federal Food, Drug, and Cosmetic
Act, the labeling bearing such
information is the labeling contained in
the index listing.
(3) Any labeling, as defined in section
201(m) of the Federal Food, Drug, and
Cosmetic Act, whether or not it is on or
within a package from which the drug
is to be dispensed, distributed by or on
behalf of the manufacturer, packer, or
distributor of the drug, that provides or
purports to provide information for use
or which prescribes, recommends, or
suggests a dosage for the use of the drug
(other than dose information required
by paragraph (c)(1)(ii) of this section)
contains:
(i) Adequate information for such use,
including indications for use, dosages,
routes of administration, frequency and
duration of administration, and any
relevant contraindications, warnings,
precautions, and adverse reactions,
including information relevant to
compliance with the new animal drug
provisions of the Federal Food, Drug,
and Cosmetic Act, under which
veterinarians licensed by law to
administer the drug can use the drug
safely and for the purposes for which it
is intended, including all conditions for
which it is advertised or represented; for
prescription new animal drugs listed in
the index of legally marketed
unapproved new animal drugs for minor
species established under section 572 of
the Federal Food, Drug, and Cosmetic
Act, the labeling components providing
such information are the same in
language and emphasis as labeling
indexed under the provisions of section
572 of the Federal Food, Drug, and
Cosmetic Act, and any other labeling
components are consistent with and not
contrary to such indexed labeling; and
(ii) The same information concerning
the ingredients of the drug as appears on
the label and labeling on or within the
package from which the drug is to be
dispensed.
(4) All labeling, except labels and
cartons, bearing information for use of
the drug also bears the date of the
issuance or the date of the latest
revision of such labeling.
(d) Reminder labeling, which calls
attention to the name of the prescription
animal drug product but does not
include indications or dosage
recommendations for use of the drug
product, is exempted from the
provisions of paragraphs (b) and (c) of
this section. This reminder labeling
must contain only the proprietary name
of the drug product, if any; the
established name of the drug product, if
any; the established name of each active
ingredient in the drug product; and,
optionally, information relating to
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quantitative ingredient statements,
dosage form, quantity of package
contents, price, the name and address of
the manufacturer, packer, or distributor
or other written, printed, or graphic
matter containing no representation or
suggestion relating to the drug product.
If the Commissioner finds that there is
evidence of significant incidence of
fatalities or serious injury associated
with the use of a particular prescription
animal drug, the Commissioner may
withdraw this exemption by so
notifying the manufacturer, packer, or
distributor of the drug by letter.
Reminder labeling, other than price lists
and catalogs solely intended to convey
price information, is not permitted for a
prescription animal drug product whose
labeling contains a boxed warning
relating to a serious hazard associated
with the use of the drug product.
■ 5. Add subpart H, consisting of
§§ 201.401 through 201.413, to read as
follows:
Subpart H—Labeling Requirements for
Approved or Conditionally Approved New
Animal Drugs
Sec.
201.401 Scope.
201.403 Definitions.
201.404 General requirements.
201.405 Content and format for prescription
new animal drug labeling.
201.407 Content and format for over-thecounter (OTC) new animal drug labeling.
201.409 Content and format of labeling for
new animal drugs for use in animal
feeds.
201.411 Exemptions from labeling
requirements for approved or
conditionally approved new animal
drugs.
201.413 Labeling requirements for certain
approved or conditionally approved new
animal drugs.
Subpart H—Labeling Requirements for
Approved or Conditionally Approved
New Animal Drugs
§ 201.401
Scope.
(a) This subpart establishes
requirements for content and format of
labeling for the following categories of
prescription (Rx) new animal drugs,
over-the-counter (OTC) new animal
drugs other than those for use in animal
feeds in accordance with part 558 of this
chapter, and new animal drugs for use
in animal feeds that are subject to part
558 of this chapter, including veterinary
feed directive (VFD) drugs:
(1) New animal drugs that are the
subject of a new animal drug
application (NADA) approved or
submitted pursuant to section 512 of the
Federal Food, Drug, and Cosmetic Act;
(2) New animal drugs that are the
subject of an application for conditional
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approval (CNADA) conditionally
approved or submitted pursuant to
section 571 of the Federal Food, Drug,
and Cosmetic Act;
(3) Generic new animal drugs that are
the subject of an abbreviated new
animal drug application (ANADA)
approved or submitted pursuant to
section 512(n) of the Federal Food,
Drug, and Cosmetic Act that references
a new animal drug for which the NADA
has been voluntarily withdrawn for
reasons other than safety or
effectiveness, or that references a new
animal drug for which the NADA has
been withdrawn on the basis of one or
more of the grounds included under
section 512(e) of the Federal Food, Drug,
and Cosmetic Act and for which the
generic new animal drug’s approval was
not affected by the withdrawal; and
(4) New animal drugs for use in
proprietary medicated feeds for which
the labeling is maintained in a
Veterinary Master File (VMF).
Proprietary medicated feeds for which
the labeling is maintained in an NADA
or CNADA are included within the
categories of drugs described in
paragraphs (a)(1) and (2) of this section.
(b) The provisions of this subpart
apply to the applications described in
paragraphs (a)(1) through (4) of this
section for new animal drugs that are
approved before the [EFFECTIVE DATE
OF THE FINAL RULE], pending on the
[EFFECTIVE DATE OF THE FINAL
RULE], or submitted on or after the
[EFFECTIVE DATE OF THE FINAL
RULE], in accordance with the schedule
in § 201.404(a)(4).
(c) Any new animal drug subject to
this subpart that does not fully comply
with the applicable requirements of this
subpart in accordance with the schedule
in § 201.404(a)(4) is deemed to be
misbranded under section 502 of the
Federal Food, Drug, and Cosmetic Act
and, if that drug is a VFD drug, also
under section 504(b) of the Federal
Food, Drug, and Cosmetic Act.
(d) The provisions of this subpart do
not apply to:
(1) Legally marketed unapproved new
animal drugs for minor species that are
indexed in accordance with section 572
of the Federal Food, Drug, and Cosmetic
Act;
(2) Heritable intentional genomic
alterations in animals; and
(3) Promotional labeling or
advertising.
§ 201.403
Definitions.
The following definitions apply to
this subpart H.
Active ingredient has the same
meaning as given in § 210.3(b)(7) of this
chapter.
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Active moiety means the molecule or
ion, excluding those appended portions
of the molecule that cause the drug to
be an ester, salt (including a salt with
hydrogen or coordination bonds), or
other noncovalent derivative (such as a
complex, chelate, or clathrate) of the
molecule, responsible for the
physiological or pharmacological action
of the drug substance.
Adverse drug experience has the same
meaning as given in § 514.3 of this
chapter.
Adverse reaction means an
undesirable effect, reasonably associated
with the use of the drug product, that
may occur as part of the
pharmacological action of the drug or
that may be unpredictable in
occurrence.
ANADA has the same meaning as
given in § 514.3 of this chapter.
Boxed warning means certain
contraindications or serious warnings,
particularly those that may lead to death
or serious injury to animals or humans
that must be presented in a box on
labeling. The box and its contents must
be bolded. The boxed warning is
ordinarily based on data from the target
animal, but data from other species may
also be used.
Contraindication means any situation
in which the new animal drug should
not be used because the risk of use (e.g.,
certain potentially fatal adverse
reactions) clearly outweighs any
possible benefit to the animal. Those
situations may include use of the drug
in animals that, because of their
particular species, class, breed, age, sex,
concomitant therapy, disease state, or
other condition such as pregnancy or
lactation, have a substantial risk of
being harmed by the drug and for which
no potential benefit makes the risk
acceptable. Contraindications include
only known hazards.
Drug product has the same meaning
as given in § 210.3(b)(4) of this chapter.
Environmental warning means a
warning that identifies any potential
hazard to the human environment
associated with the use of the new
animal drug.
Established name has the same
meaning as given in section 502(e)(3) of
the Federal Food, Drug, and Cosmetic
Act.
Extralabel use has the same meaning
as given in § 530.3(a) of this chapter.
Field study means a type of adequate
and well-controlled study designed to
assess the effectiveness and/or safety of
a new animal drug in the target animal
under conditions that closely
approximate the actual conditions of
use.
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Free-choice medicated feed has the
same meaning as given in § 510.455(a)
of this chapter.
Full prescribing information means all
information necessary for the safe and
effective use of a Rx new animal drug.
Full product information means all
information necessary for the safe and
effective use of an OTC new animal
drug.
Immediate container means the
container in contact with the new
animal drug. The term ‘‘immediate
container’’ does not include package
liners (section 201(l) of the Federal
Food, Drug, and Cosmetic Act).
Inactive ingredient has the same
meaning as given in § 210.3(b)(8) of this
chapter.
Indication means the use for which
the new animal drug is approved or
conditionally approved.
Label has the same meaning as given
in section 201(k) of the Federal Food,
Drug, and Cosmetic Act.
Labeling has the same meaning as
given in section 201(m) of the Federal
Food, Drug, and Cosmetic Act.
Lot number, control number, or batch
number has the same meaning as given
in § 210.3(b)(11) of this chapter.
Milk discard time means the interval
between the time of the last
administration of a new animal drug
and the time when the milk can be
safely consumed.
NADA has the same meaning as given
in § 514.3 of this chapter.
New animal drug has the same
meaning as given in section 201(v) of
the Federal Food, Drug, and Cosmetic
Act.
Package insert means a labeling
component that contains full
prescribing information for Rx new
animal drugs or full product
information for OTC new animal drugs
and is included with the immediate
container or secondary container or is
attached to the label.
Precaution means any special care to
be exercised for safe and effective use of
the new animal drug. This may include
recommended screening, monitoring, or
diagnostic tests.
Representative Type B medicated feed
labeling means template labeling (also
known as ‘‘Blue Bird labels,’’ 64 FR
63197, November 19, 1999) approved by
FDA as part of the new animal drug
application or an application for
conditional approval for a Type A
medicated article for the preparation of
final printed labels (for medicated feed
bags) or labeling (accompanying bulk
medicated feed) for Type B medicated
feeds containing the new animal drug.
Representative Type B medicated feed
labeling provides the minimum
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information that must be included on
the final printed labels or labeling for
Type B medicated feeds.
Representative Type C medicated feed
labeling means template labeling (also
known as ‘‘Blue Bird labels,’’ 64 FR
63197, November 19, 1999) approved by
FDA as part of the new animal drug
application or an application for
conditional approval for a Type A
medicated article or proprietary Type B
medicated feed for the preparation of
final printed labels (for medicated feed
bags) or labeling (accompanying bulk
medicated feed) for Type C medicated
feeds containing the new animal drug.
Representative Type C medicated feed
labeling provides the minimum
information that must be included on
the final printed labels or labeling for
Type C medicated feeds.
Residue warning statement means a
statement that warns against the use of
the new animal drug in animals for
which the withdrawal period and/or
milk discard time has not been
determined, and/or provides other
information to prevent illegal drug
residues in food products from animals
treated with the new animal drug.
Secondary container means the
packaging that surrounds the immediate
container for a new animal drug.
Shipping labeling means labeling
associated with the outermost carton
containing immediate containers,
secondary containers, and/or multiple
unit (multi-unit) cartons of a new
animal drug and intended for shipment,
but not display, of the product.
Small label means a label on an
immediate container for a new animal
drug that has insufficient space to
accommodate the information required
for a label by § 201.405(b) for Rx new
animal drugs or § 201.407(b) for OTC
new animal drugs.
Sponsor has the same meaning as
given in § 510.3(k) of this chapter.
Strength has the same meaning as
given in § 210.3(b)(16) of this chapter.
Target animal means the species, or
collection of species, of animals, and, if
applicable, the specific subset(s) of
animals (e.g., life stage, production
class, age, gender) for which the new
animal drug is approved or
conditionally approved.
Type A medicated article has the
same meaning as given in § 558.3(b)(2)
of this chapter.
Type B medicated feed has the same
meaning as given in § 558.3(b)(3) of this
chapter.
Type C medicated feed has the same
meaning as given in § 558.3(b)(4) of this
chapter.
User safety warning means a warning
that identifies any serious adverse
reaction or potential hazard to human
health associated with human exposure
during use of a new animal drug via
contact, inhalation, ingestion, injection,
or by other means.
Veterinary feed directive (VFD) has
the same meaning as given in
§ 558.3(b)(7) of this chapter.
VFD drug has the same meaning as
given in § 558.3(b)(6) of this chapter.
Warning means any serious adverse
reaction or potential hazard associated
with the use of the new animal drug.
Withdrawal period means the interval
between the time of the last
administration of a new animal drug
and the time when the animal can be
safely slaughtered for food.
§ 201.404
General requirements.
(a) The labeling of a new animal drug
subject to these regulations as identified
in § 201.401(a):
(1) Must conform to an application
approved under section 512 of the
Federal Food, Drug, and Cosmetic Act
or conditionally approved under section
571 of the Federal Food, Drug, and
Cosmetic Act.
(2) Must be informative and accurate
and neither promotional in tone nor
false or misleading in any particular.
(3) Must be updated if new
information becomes available that
causes the labeling to become
inaccurate, false, or misleading, in
accordance with § 514.8 of this chapter.
(4) Must conform to this subpart in
accordance with the earliest applicable
compliance date provided in the
following schedule, unless paragraphs
(b), (c), or (d) of this section are
applicable.
TABLE 1 TO PARAGRAPH (a)(4)
Application No. and/or status
All conforming labeling must be submitted:
(i) NADA, CNADA, or a supplement to an NADA or CNADA subject to
§ 514.8(c)(2) submitted after [effective date of the final rule plus 180
days].
(ii) NADA, CNADA, or a supplement to an NADA or CNADA subject
to § 514.8(c)(2) pending on [effective date of the final rule] or submitted between [effective date of the final rule] and [effective date of
the final rule plus 180 days].
(iii) NADA number 141–300 or greater and originally approved before
[effective date of the final rule]; or ANADA that references an NADA
(1) voluntarily withdrawn for reasons other than safety and effectiveness, or (2) withdrawn under section 512(e) of the Federal Food,
Drug, and Cosmetic Act and the ANADA’s approval was not affected by the withdrawal.
(iv) NADA number 141–000 to 141–299 ................................................
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(v) NADA number 115–000 to 140–999 .................................................
(vi) NADA number 45–000 to 114–999 ..................................................
(vii) NADA number 1 to 44–999 .............................................................
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As part of the application or supplemental application.
As part of the application or supplemental application; or, as a supplement to an approved application or supplemental application no
later than 180 days after the approval date of the application or
supplemental application.
As a supplement to an approved application between [effective date
of the final rule plus 1 year] and [effective date of the final rule plus
2 years].
As a supplement to an
of the final rule plus
plus 3 years].
As a supplement to an
of the final rule plus
plus 4 years].
As a supplement to an
of the final rule plus
plus 5 years].
As a supplement to an
of the final rule plus
plus 6 years].
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approved application between [effective date
2 years] and [effective date of the final rule
approved application between [effective date
3 years] and [effective date of the final rule
approved application between [effective date
4 years] and [effective date of the final rule
approved application between [effective date
5 years] and [effective date of the final rule
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(b) For proprietary Type B or Type C
medicated feeds in which the
underlying data and labeling are
maintained in a VMF, a submission
containing the conforming labeling must
be made to the VMF within 180 days
after all conforming labeling has been
approved for the NADA or CNADA that
is the approved or conditionally
approved source of the new animal drug
used to manufacture the proprietary
medicated feed.
(c) Unless a supplement subject to
§ 514.8(c)(2) of this chapter is submitted
to a CNADA after the [effective date of
the final rule], new animal drugs
conditionally approved before [effective
date of the final rule] are not required
to conform to this subpart until an
application for full approval is
submitted.
(d) For combination new animal drugs
subject to section 512(d)(4) of the
Federal Food, Drug, and Cosmetic Act
that are approved for use in animal feed
or drinking water on or before [effective
date of the final rule], a supplement
containing the conforming labeling for
the combination new animal drug must
be submitted within 180 days after all
conforming labeling has been approved
for the individual new animal drugs in
the combination.
(e) In those circumstances where it
may not be clear how a requirement in
this subpart applies to a particular new
animal drug, or whether it applies, the
final determination will be made by
FDA.
(f) When submitting labeling for the
purposes of conforming to the
requirements of subpart H according to
the schedule in paragraph (a)(4) of this
section, all labeling components for the
approved or conditionally approved
new animal drug must be provided in
one submission. FDA will refuse to file
labeling submissions intended to
conform to this subpart if they are
incomplete.
(g) All labeling for an approved or
conditionally approved new animal
drug must comply with the general
formatting requirements described in
this paragraph in addition to all content
and formatting requirements described
in this subpart.
(1) Placement of the established name
relative to the proprietary name on
labeling for approved or conditionally
approved Rx new animal drugs must
comply with § 201.10(g)(1). Size and
prominence of the established name
relative to the proprietary name must
comply with section 502(e)(1)(B) of the
Federal Food, Drug, and Cosmetic Act
and § 201.10(g)(2).
(2) Placement, size, and prominence
of the established name relative to the
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proprietary name on the labeling for
approved or conditionally approved
OTC new animal drugs and the labeling
for approved or conditionally approved
new animal drugs for use in animal
feeds (Type A medicated article label,
proprietary Type B medicated feed
label, proprietary Type C medicated
feed label, other approved labeling
associated with a Type A medicated
article), excluding representative Type B
and Type C medicated feed labeling,
must comply with the following
requirements:
(i) The proprietary name of the new
animal drug must be accompanied by
the established name each time the
proprietary name is featured on the
labeling, except in running text.
Running text includes detailed
information such as found in warnings
and directions. On any panel or page of
a component of labeling in which the
proprietary name is not featured
elsewhere but is used in the running
text, the established name must be
placed in conjunction with the
proprietary name at least with the first
presentation of the proprietary name in
running text.
(ii) Where the established name
accompanies the proprietary name, it
must be placed directly to the right of,
or directly below, the proprietary name.
Except for trademark symbols associated
with the proprietary name, the
proprietary name and the established
name must not be separated by
placement of intervening matter that, in
any way, detracts from, obfuscates, or
de-emphasizes the established name of
the product, or obscures the relationship
between the proprietary name and the
established name. The established name
must be presented entirely within
parentheses.
(iii) Except in running text, where the
established name accompanies the
proprietary name, the smallest letter of
the established name (upper or lower
case letters) must be printed in letters at
least half the size of the largest letter of
the proprietary name (upper or lower
case letters). Within running text, the
established name accompanying the
proprietary name must be printed in
letters the same size of the letters in the
proprietary name (upper and lower case
letters). The prominence of the
established name must be consistent
with the prominence of the proprietary
name, taking into account all pertinent
factors including typography, layout,
contrast, and other printing features.
(3) For representative Type B and
Type C medicated feed labeling for
approved or conditionally approved
new animal drugs for use in animal
feeds, the established name of the Type
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18319
B or Type C medicated feed presented
below the description of the Type B or
Type C medicated feed must comply
with the following requirements:
(i) The established name must be
presented directly below the description
of the Type B or Type C medicated feed
and must not be separated by placement
of intervening matter.
(ii) The established name must be
printed in lower case letters except for
‘‘Type B’’ or ‘‘Type C’’.
(iii) The established name must be
printed in non-bold font of the same
size letters as the name of the Type B
or Type C medicated feed (upper and
lower case letters).
(iv) The established name must be
presented entirely within parentheses.
(4) All labeling text and type style
must be easy to read, and letters must
not touch.
(5) Running text, section headings,
and subsection headings on package
inserts and representative Type B and
Type C medicated feed labeling must be
in black and on a white background and
use a single type style. For other
labeling components, other color
combinations may be used if there is
sufficient contrast between text and the
background colors to ensure readability
of the text.
(6) Representative Type B and Type C
medicated feed labeling must not
contain any logos, graphics, or designs
other than illustrations or tables that
FDA determines are necessary for
proper use of the medicated feed. For
other labeling components for approved
or conditionally approved new animal
drugs, in accordance with § 201.15(b)(1),
graphics or designs associated with the
labeling must not take up space needed
for information required by this subpart.
In accordance with paragraph (a)(2) of
this section, graphics or diagrams must
not be promotional in tone. If graphics
are incorporated into the background,
for any text appearing over the graphics,
there must be sufficient contrast
between the text and the graphics colors
to ensure readability of the text. The use
of compressed arrows on labeling is
limited to the subsection entitled either
‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods,’’ in
accordance with paragraph (g)(8)(iii) of
this section.
(7) The following minimum letter
height or type size must be used for
specific components of labeling, subject
to the provisions of paragraph (g)(2) of
this section:
(i) Immediate container label,
secondary container labeling, package
inserts, and labeling of multiple unit
cartons and display cartons: 8 points.
(ii) Small label: 6 points.
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(iii) Type A medicated article label,
representative Type B medicated feed
labeling, representative Type C
medicated feed labeling, proprietary
Type B medicated feed label, and
proprietary Type C medicated feed
label: 10 points.
(iv) Additional labeling for Rx new
animal drugs that is to be provided to
the animal owner: 12 points.
(v) Shipping labeling for Rx and OTC
new animal drugs and other approved
labeling for Type A medicated articles:
16 points.
(8) Section headings and subsection
headings must be formatted as follows:
(i) All section headings and
subsection headings must be in bold
type that prominently distinguishes
them from other approved labeling
information.
(ii) Section headings must be either
left justified or centered.
(iii) For the subsection entitled either
‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods,’’
the subsection heading, and the
contents of the subsection, must be
centered within compressed arrows.
(iv) All other subsection headings
must be left justified.
(h) If the National Drug Code (NDC)
is included on labeling, it must appear
in accordance with § 207.33 of this
chapter.
(i) All words, statements, and other
information required on the labeling for
approved or conditionally approved
new animal drugs must appear in the
English language. Additional
translations of labeling for approved or
conditionally approved new animal
drugs into foreign languages must
comply with the following
requirements:
(1) For approved or conditionally
approved Rx new animal drugs, if a
labeling component contains any
section or wording translated into a
foreign language, then the entire full
prescribing information must be
translated into the foreign language and
must comply with the format and
content requirements in § 201.405(a).
FDA also may require additional
wording on other labeling components
for the Rx new animal drug to be
translated into the foreign language
when necessary to ensure its safe and
effective use.
(2) For approved or conditionally
approved OTC new animal drugs other
than new animal drugs for use in animal
feeds, if a labeling component contains
any section or wording translated into a
foreign language, then the entire full
product information must be translated
into the foreign language and must
comply with the format and content
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requirements in § 201.407(a). FDA also
may require additional wording on
other labeling components for the OTC
new animal drug to be translated into
the foreign language when necessary to
ensure its safe and effective use.
(3) For approved or conditionally
approved new animal drugs for use in
animal feeds, if the labeling contains
any section or wording translated into a
foreign language, then all labeling must
be translated into the foreign language
and must comply with the format and
content requirements in § 201.409.
(4) FDA may limit the number of
languages into which labeling
information is translated to ensure
clarity of information and the safe and
effective use of the new animal drug.
(j) For approved or conditionally
approved new animal drugs distributed
solely in the Commonwealth of Puerto
Rico or in a Territory where the
predominant language is other than
English, the predominant language may
be substituted for English. Such new
animal drugs may be exempt from
paragraph (i) of this section.
§ 201.405 Content and format for
prescription (Rx) new animal drug labeling.
This section describes specific
content and format requirements for the
labeling of approved or conditionally
approved Rx new animal drugs. This
section does not apply to new animal
drugs approved or conditionally
approved as veterinary feed directive
(VFD) drugs. See § 201.409 for content
and format requirements for the labeling
of approved or conditionally approved
new animal drugs for use in animal
feeds that are subject to part 558 of this
chapter, including VFD drugs. Omit
labeling sections or subsections that do
not apply to the Rx new animal drug.
The final content of each applicable
component and section of labeling is
determined by FDA. In addition to the
content and format requirements in this
section, the labeling of approved or
conditionally approved Rx new animal
drugs must comply with other
applicable requirements in this subpart.
(a) Labeling providing full prescribing
information. All approved or
conditionally approved Rx new animal
drugs must provide full prescribing
information as described in this
paragraph. The package insert must
include full prescribing information. If
no package insert is provided, a
secondary container is required, and its
labeling must include full prescribing
information as described in this
paragraph. The following information,
as applicable, must appear in the order
listed on the labeling component
providing full prescribing information.
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If full prescribing information is
provided on the secondary container
labeling, in accordance with section
201(k) of the Federal Food, Drug, and
Cosmetic Act, the secondary container
labeling may exclude any of the
information described in this subsection
that is required by paragraphs (b) or (c)
of this section to appear on the label if
such information is easily legible
through the secondary container.
Section headings, subsection headings,
and other text presented in quotations
in this paragraph must appear verbatim
on the labeling providing full
prescribing information. Sections and
subsections are not numbered on full
prescribing information.
(1) Drug product identification. This
section of full prescribing information
must include:
(i) The proprietary name of the
finished drug product;
(ii) The established name of the drug
product;
(iii) The route(s) of administration, if
not included as part of the established
name of the drug product;
(iv) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(v) The established name and strength
or concentration of each active
ingredient, except that the strength or
concentration may be excluded from
full prescribing information provided on
a package insert that applies to multiple
strengths or concentrations;
(vi) The pharmacological class of the
new animal drug, if required to facilitate
the drug’s safe and effective use; and
(vii) For controlled substances, the
required controlled substance symbol,
in accordance with part 1302 of this title
designating the schedule for the drug
substance.
(2) Prescription statement. This
section of full prescribing information
must include the following statement:
‘‘Caution: Federal law restricts this drug
to use by or on the order of a licensed
veterinarian’’.
(3) Conditional approval statement.
All conditionally approved new animal
drugs must include the following
statement in this section of full
prescribing information in accordance
with section 571(f)(1)(A) of the Federal
Food, Drug, and Cosmetic Act:
‘‘conditionally approved by FDA
pending a full demonstration of
effectiveness under application number
[insert number]’’. This statement must
be prominent and conspicuous.
(4) Boxed warnings. All Rx new
animal drugs with boxed warnings must
include the boxed warning in this
section of full prescribing information.
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The box must contain, in upper case
letters, the heading ‘‘WARNING’’. The
contents of the box must briefly explain
the risk and, if appropriate, refer to
more detailed information in other
sections of full prescribing information.
The box, heading, and contents must be
bolded.
(5) Extralabel use prohibition
statement. An approved new animal
drug that is prohibited from extralabel
use as listed under § 530.41 of this
chapter must include in this section of
full prescribing information an
extralabel use prohibition statement that
begins with the phrase: ‘‘Federal law
prohibits the extralabel use of this drug
. . .’’ and concludes with a description
of the prohibition as described in
§ 530.41 of this chapter.
(6) ‘‘Description’’. This section of full
prescribing information must include:
(i) The proprietary name of the
finished drug product;
(ii) The established name of the drug
product;
(iii) The route(s) of administration, if
not included as part of the established
name of the drug product;
(iv) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(v) A description of the identifying
characteristics of the dosage form, such
as color, shape, coating, scoring, and
imprinting;
(vi) The established name and
strength or concentration of each active
ingredient, including all available
strengths or concentrations to which full
prescribing information applies;
(vii) If applicable, a statement that the
product is sterile; and
(viii) The established name of each
inactive ingredient presented in
decreasing order of predominance, by
weight or concentration.
(A) If exemption from listing one or
more inactive ingredients is granted, in
accordance with § 201.411, to avoid
disclosure of trade secret information,
this section of full prescribing
information must also state the
following: ‘‘Certain inactive ingredients
are not listed to avoid disclosing trade
secret information.’’
(B) If exemption from listing one or
more inactive ingredients is granted, in
accordance with § 201.411, because
their listing would be impracticable,
this section of full prescribing
information must also state the
following: ‘‘Certain inactive ingredients
are not listed because their listing
would be impracticable.’’
(7) ‘‘Indications for Use’’. Include the
following information in this section of
full prescribing information in order:
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(i) The approved or conditionally
approved indication(s) and target
animal(s) in the following format: ‘‘For
[indication(s)] in [target animal(s)]’’;
(ii) A statement indicating that the
new animal drug is approved or
conditionally approved for use only
under specific conditions, if applicable;
and
(iii) A statement(s) indicating animals
for which the new animal drug is not
approved or conditionally approved, if
FDA determines such a statement(s) is
required for safety and/or effectiveness
reasons.
(8) ‘‘Dosage and Administration’’.
This section of full prescribing
information must include for each
indication and target animal:
(i) The statement, ‘‘Always provide
[additional labeling] with each
prescription’’ for Rx new animal drugs
requiring additional labeling, in
accordance with paragraph (a)(14) of
this section, inserting the title of the
additional labeling in the location
indicated by the bracketed text;
(ii) The route(s) of administration, and
specific site(s) of administration, if
applicable;
(iii) The dose (or dose range);
(iv) The intervals between doses, if
applicable;
(v) The duration of treatment;
(vi) The maximum volume per
injection site, if required to facilitate the
drug’s safe and effective use;
(vii) Any modification of the
information required in paragraphs
(a)(8)(i) through (vi) of this section that
is needed for special animal populations
(e.g., neonatal, reproducing, lactating,
geriatric, or those with specific disease
states); and
(viii) Other information regarding
dosage and administration, if required
to facilitate the drug’s safe and effective
use.
(9) ‘‘Contraindications’’. All Rx new
animal drugs with contraindications
must include the contraindications in
this section of full prescribing
information.
(10) ‘‘Warnings and Precautions’’.
This section of full prescribing
information is required for all approved
or conditionally approved Rx new
animal drugs. Include in the following
order all applicable subsections,
headings, and information:
(i) ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods’’.
This subsection of full prescribing
information is required for all new
animal drugs approved or conditionally
approved for use in food-producing
animals and must include all human
food safety warnings, including milk
discard times, withdrawal periods, and
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residue warning statements, as
applicable. The order of the human food
safety warnings in this subsection of full
prescribing information must be as
described in paragraphs (a)(10)(i)(B)
through (G) of this section, as
applicable.
(A) If there is a residue warning
statement(s), this subsection of full
prescribing information must be entitled
‘‘Withdrawal Periods and Residue
Warnings’’. If there is no residue
warning statement, this subsection of
full prescribing information must be
entitled ‘‘Withdrawal Periods’’. The title
of this subsection and all information in
this subsection of full prescribing
information must be centered and
placed entirely within compressed
arrows, in accordance with
§ 201.404(g)(8). The compressed arrows
must be black for package inserts or a
color that clearly contrasts from
background colors for other approved
labeling.
(B) If the new animal drug is
approved or conditionally approved for
use in food-producing animals
excluding female animals that produce
milk for human consumption, include
in this subsection of full prescribing
information the withdrawal period(s)
followed by any residue warning
statements.
(C) If the new animal drug is
approved or conditionally approved for
use in food-producing animals
excluding female animals that produce
milk for human consumption and there
is no withdrawal period, include in this
subsection of full prescribing
information the statement ‘‘No
withdrawal period is required when
used according to labeling.’’, followed
by any residue warning statements.
(D) If the new animal drug is
approved or conditionally approved for
use in female animals that produce milk
for human consumption, include in this
subsection of full prescribing
information the milk discard time(s),
followed by the withdrawal period(s),
followed by any residue warning
statements.
(E) If the new animal drug is approved
or conditionally approved for use in
female animals that produce milk for
human consumption and there is a milk
discard time(s) but no withdrawal
period, include in this subsection of full
prescribing information the milk discard
time(s), followed by the statement ‘‘No
withdrawal period is required when
used according to labeling.’’, followed
by any residue warning statements.
(F) If the new animal drug is approved
or conditionally approved for use in
female animals that produce milk for
human consumption and there is no
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milk discard time but there is a
withdrawal period(s), include in this
subsection of full prescribing
information the withdrawal period(s),
followed by the statement ‘‘No milk
discard time is required when used
according to labeling.’’, followed by any
residue warning statements.
(G) If the new animal drug is
approved or conditionally approved for
use in female animals that produce milk
for human consumption and there is no
milk discard time and no withdrawal
period, include in this subsection of full
prescribing information the statement
‘‘No milk discard time and no
withdrawal period is required when
used according to labeling.’’, followed
by any residue warning statements.
(ii) ‘‘User Safety Warnings’’. This
subsection of full prescribing
information is required for all new
animal drugs and must include in the
following order:
(A) ‘‘Not for use in humans. Keep out
of reach of children.’’
(B) All additional user safety
warnings listed in decreasing order of
severity or frequency; and
(C) ‘‘To obtain a Safety Data Sheet(s),
contact [insert name of manufacturer] at
[insert manufacturer’s telephone
number] or [insert manufacturer’s
website].’’
(iii) ‘‘Animal Safety Warnings and
Precautions’’. All target animal safety
warnings that identify any serious
adverse reaction or potential hazard to
the target animal(s) associated with the
use of the new animal drug and all
precautions must be included in this
subsection of full prescribing
information. These items must be listed
in decreasing order of severity or
frequency.
(iv) ‘‘Environmental Warnings’’. All
environmental warnings applicable to
the new animal drug that are included
in an approved or conditionally
approved application must be provided
in this subsection of full prescribing
information.
(v) ‘‘Other Warnings’’. Any other
required warnings must be included in
this subsection of full prescribing
information.
(11) ‘‘Adverse Reactions’’. Include in
this section of full prescribing
information the adverse reactions, as
determined by FDA, that occur with use
of the Rx new animal drug and with use
of drugs in the same pharmacologically
active and chemically related class, if
applicable. Include information
necessary to interpret the adverse
reactions (e.g., for field studies include
total number of animals exposed, extent
and nature of exposure). Within the
following categories, as applicable,
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present the adverse reactions in
decreasing order of severity or
frequency.
(i) ‘‘Pre-approval experience’’. Include
adverse reactions observed in laboratory
or field studies in the target animal(s).
(ii) ‘‘Foreign market experience’’. If
the drug product has been commercially
marketed outside the United States,
include information from foreign
adverse drug experience reports known
prior to U.S. approval.
(iii) ‘‘Post-approval experience’’.
Include the adverse reactions identified
from domestic and foreign adverse drug
experience reports.
(12) ‘‘Contact Information’’. The
following statements must be included
in this section of full prescribing
information: ‘‘Contact [insert name of
business] at [insert business telephone
number] or [insert business web
address]. To report suspected adverse
drug experiences, contact [insert name
of business] at [insert business
telephone number]. For additional
information about reporting adverse
drug experiences for animal drugs,
contact FDA at [insert current FDA
telephone number for voluntary
reporting of adverse drug experiences]
or [insert current FDA web address for
voluntary reporting of adverse drug
experiences].’’ Use as the name of the
business the manufacturer, packer, or
distributor identified in the ‘‘Name and
place of business’’ section of full
prescribing information according to
paragraph (a)(22) of this section. If more
than one business is identified in the
‘‘Name and place of business’’ section of
full prescribing information, select the
most appropriate to identify as the
‘‘business’’ in the ‘‘Contact Information’’
section of full prescribing information to
provide additional information about
the Rx new animal drug and to contact
regarding suspected adverse drug
experiences.
(13) ‘‘Information for Animal Owner’’.
Any specific information that FDA
determines is necessary for the animal
owner or person treating the animal to
use the Rx new animal drug safely and
effectively must be included in this
section of full prescribing information.
If FDA requires additional labeling (e.g.,
a client information sheet), a printed
copy must be attached to, or
accompany, the package insert or
secondary container labeling if no
package insert is provided.
(14) ‘‘Clinical Pharmacology’’. If
required by FDA to facilitate the drug’s
safe and effective use, include a
summary of the clinical pharmacology
of the Rx new animal drug in the target
animal(s) in this section of full
prescribing information, including the
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following three subsections, as
applicable:
(i) ‘‘Mechanism of action’’;
(ii) ‘‘Pharmacodynamics’’; and
(iii) ‘‘Pharmacokinetics’’.
(15) ‘‘Microbiology’’. This section of
full prescribing information is required
for all antimicrobial Rx new animal
drugs and must include a description of
microbiologic data associated with the
studies used to support the effectiveness
of the drug against the indicated
pathogens. Microbiology data must be
restricted to organisms named in the
approved or conditionally approved
indications. If in vitro data for
antimicrobial new animal drugs are
included in this section of full
prescribing information that have not
been correlated to clinical effectiveness,
the data must be immediately preceded
by the statement: ‘‘The following in
vitro data are available, but their clinical
significance is unknown.’’
(16) ‘‘Target Animal Safety’’. This
section of full prescribing information
must include a summary of the basis for
the conclusion that the new animal drug
is safe in the target animal(s) when used
as approved or conditionally approved.
(17) ‘‘Effectiveness’’. This section of
full prescribing information must
include a summary of the basis for the
conclusion that the new animal drug is
effective in the target animal(s) when
used as approved. For a conditionally
approved new animal drug, include a
summary of the basis for the reasonable
expectation of effectiveness.
(18) ‘‘Net Contents’’. This section of
full prescribing information must
identify the contents of the secondary
container. Exclude this section from
package inserts.
(19) ‘‘How Supplied’’. This section of
full prescribing information must
include information on the available
drug strengths, concentrations, and
container sizes to which the labeling
applies. Revise this section of full
prescribing information if new
strengths, concentrations, or container
sizes are added.
(20) ‘‘Storage, Handling, and
Disposal’’. This section of full
prescribing information must include
drug storage information. Also include
any required handling and drug
disposal information in this section.
(21) NADA/ANADA approval
statement. In accordance with section
502(w)(3) of the Federal Food, Drug, and
Cosmetic Act, approved new animal
drugs must include the following
statement in this section of full
prescribing information: ‘‘Approved by
FDA under NADA # xxx–xxx’’.
Approved generic new animal drugs
must include the following statement in
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this section of full prescribing
information: ‘‘Approved by FDA under
ANADA # xxx-xxx’’. This statement
must appear in this section of full
prescribing information and:
(i) Appear on one straight line unless
there is insufficient space, in which case
the statement may appear on two
straight lines;
(ii) Not be incorporated into a seal,
stamp, logo or other graphic;
(iii) Be of consistent type size, color,
and contrast and be of no greater
prominence than the rest of the labeling
text; and
(iv) Not obscure or otherwise render
less conspicuous any word, statement,
or other information required by FDA.
(22) Name and place of business. This
section of full prescribing information
must include the name and place of
business of the manufacturer, packer, or
distributor.
(23) ‘‘Lot Number and Expiration
Date’’. This section is required when
full prescribing information is provided
on the secondary container labeling.
This section must include the
identifying lot or control number of the
Rx new animal drug within the
secondary container. This section must
also include the expiration date of the
Rx new animal drug within the
secondary container, in accordance with
§ 201.17. Alternatively, this section
must refer to the location on the
secondary container labeling or
secondary container where the lot or
control number and expiration date are
printed. In accordance with § 201.17, an
expiration date may be excluded from
the secondary container labeling or
secondary container if the expiration
date provided on the label or immediate
container is easily legible through the
secondary container.
(24) ‘‘Revision Date’’. This section of
full prescribing information must
include the date of the most recent
revision of the component of labeling
that provides full prescribing
information, listing the month followed
by the year.
(b) Prescription new animal drug label
(Rx label). All approved or conditionally
approved Rx new animal drugs must
provide a label (Rx label). The following
information, as applicable, must appear
in the order listed on the Rx label. If
there is insufficient space on the
immediate container for a label to
provide for all of the following
information, then an Rx small label is
required instead. The requirements for
an Rx small label are provided in
paragraph (c) of this section. Section
headings and other text presented in
quotations in this paragraph must
appear verbatim on the Rx label.
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Sections are not numbered on the Rx
label. For Rx labels with a front panel
and one side or back panel, the
information identified in paragraph
(b)(1) of this section must be provided
on the front panel in the order listed,
and the information identified in
paragraph (b)(2) of this section must be
provided on the side or back panel in
the order listed. If the Rx label consists
of a single panel, the information
identified in paragraph (b)(1) must be
provided on the Rx label in the order
listed followed by the information
identified in paragraph (b)(2) in the
order listed. For Rx labels with a front
panel and multiple side and/or back
panels, the information identified in
paragraph (b)(1) must be provided on
the Rx label in the order listed followed
by the information identified in
paragraph (b)(2) in the order listed,
starting on the front panel, continuing
on the panel immediately to the right of
the front panel, and continuing to fill
the panels to the right until all of the
information is presented. In all
instances, the information specified in
paragraphs (b)(2)(iii) and (iv) must
appear on the same panel.
(1) Front panel. The following
information must appear on the front
panel of the Rx label in the order listed.
(i) Drug product identification. This
section of the Rx label must include:
(A) The proprietary name of the
finished drug product;
(B) The established name of the drug
product;
(C) The route(s) of administration, if
not included as part of the established
name of the drug product;
(D) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(E) The established name and strength
or concentration of each active
ingredient;
(F) If applicable, a statement that the
product is sterile;
(G) The pharmacological class of the
new animal drug, if required to facilitate
the drug’s safe and effective use; and
(H) For controlled substances, the
required controlled substance symbol,
in accordance with part 1302 of this title
designating the schedule for the drug
substance.
(ii) Prescription statement. This
section of the Rx label must include the
following statement, in accordance with
section 503(f)(4) of the Federal Food,
Drug, and Cosmetic Act: ‘‘Caution:
Federal law restricts this drug to use by
or on the order of a licensed
veterinarian.’’
(iii) Conditional approval statement.
For conditionally approved new animal
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drugs, the requirements of paragraph
(a)(3) of this section apply.
(iv) Boxed warnings. For Rx new
animal drugs that have boxed warnings,
the requirements of paragraph (a)(4) of
this section apply.
(v) ‘‘Indications for Use’’. The
requirements of paragraph (a)(7) of this
section apply. However, if there is
insufficient space on the Rx label for the
complete ‘‘Indications for Use’’ section
as specified in paragraph (a)(7), then
include the statement required in
paragraph (a)(7)(i) or, if there is
insufficient space on the Rx label for the
statement in paragraph (a)(7)(i), then
include the statement, ‘‘For [abbreviated
indication(s)] in [target animal(s)]’’. In
either situation where there is
insufficient space on the Rx label for the
complete ‘‘Indications for Use’’ section
as specified in paragraph (a)(7), the
required statement must be followed by,
‘‘See package insert for complete
‘Indications for Use’’’ if full prescribing
information is provided on a package
insert, or ‘‘See package labeling for
complete ‘Indications for Use’’’ if full
prescribing information is provided on
the secondary container labeling.
(vi) Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use as
listed under § 530.41 of this chapter, the
requirements of paragraph (a)(5) of this
section apply.
(vii) ‘‘Withdrawal Periods and
Residue Warnings’’ or ‘‘Withdrawal
Periods’’. For new animal drugs
approved or conditionally approved for
use in food-producing animals, the
requirements of paragraph (a)(10)(i) of
this section apply. If there is insufficient
space on the front panel of Rx labels
consisting of only a front panel and one
side or back panel for the information
required in paragraph (a)(10)(i), this
section must be provided on the side or
back panel of the Rx label immediately
following the full prescribing
information statement specified in
paragraph (b)(2)(i) of this section.
(viii) ‘‘Net Contents’’. This section of
the Rx label must identify the contents
of the immediate container, in
accordance with § 201.5.
(ix) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of paragraph
(a)(21) of this section apply.
(2) Side or back panel. The following
information must appear on the side or
back panel of the Rx label in the order
listed.
(i) Full prescribing information
statement. This section of the Rx label
must include one of two statements. If
full prescribing information is provided
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on the package insert, the following
statement must be used: ‘‘Before using
this drug, read package insert for full
prescribing information.’’ If full
prescribing information is provided on
the secondary container labeling, the
following statement must be used:
‘‘Before using this drug, read package
labeling for full prescribing
information.’’
(ii) ‘‘Dosage and Administration’’.
The requirements of paragraph (a)(8) of
this section apply. If there is insufficient
space on the Rx label for the complete
requirements as specified in paragraph
(a)(8) or if it is necessary for additional
information provided in full prescribing
information that is not provided on the
Rx label to be read before administering
the drug, FDA may allow this section to
be excluded from the Rx label.
(iii) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the Rx
label must provide the established name
and strength or concentration of each
active ingredient. If the Rx new animal
drug contains one active ingredient, this
section of the Rx label must be entitled
‘‘Active Ingredient’’. If the Rx new
animal drug contains more than one
active ingredient, this section of the Rx
label must be entitled ‘‘Active
Ingredients.’’
(iv) ‘‘Inactive Ingredients’’. The
requirements of paragraph (a)(6)(viii) of
this section apply.
(v) ‘‘Storage, Handling, and
Disposal’’. The requirements of
paragraph (a)(20) of this section apply.
(vi) Name and place of business. This
section of the Rx label must include the
name and place of business of the
manufacturer, packer, or distributor, in
accordance with section 502(b) of the
Federal Food, Drug, and Cosmetic Act.
(vii) ‘‘Lot Number and Expiration
Date’’ or ‘‘Lot Number’’. This section of
the Rx label must include the
identifying lot or control number of the
Rx new animal drug within the
immediate container. This section of the
Rx label must also include the
expiration date of the Rx new animal
drug within the immediate container, in
accordance with § 201.17. Alternatively,
this section must refer to the location on
the Rx label or immediate container
where the lot or control number and
expiration date are printed. In
accordance with § 201.17, if the
immediate container provides a single
dose of the Rx new animal drug and is
packaged individually in a secondary
container that provides an expiration
date on the secondary container labeling
or secondary container, an expiration
date is not required on the Rx label or
immediate container. If an expiration
date is not provided on the Rx label or
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immediate container per this provision,
then this section of the Rx label must be
entitled ‘‘Lot Number.’’
(viii) ‘‘Revision Date’’. This section of
the Rx label must include the date of the
most recent revision of the Rx label,
listing the month followed by the year.
(c) Prescription new animal drug
small label (Rx small label). The
following information, as applicable,
must appear in the order listed on the
Rx small label. FDA will make the final
determination as to whether an
immediate container lacks sufficient
space for the label to include all of the
information required by paragraph (b) of
this section, taking into consideration
readability and legibility of the
information. Section headings and other
text presented in quotations in this
paragraph must appear verbatim on the
Rx small label. Sections are not
numbered on the Rx small label.
(1) Proprietary name. This section of
the Rx small label must provide the
proprietary name of the finished drug
product.
(2) Established name. This section of
the Rx small label must provide the
established name of the drug product.
(3) Active ingredient(s). This section
of the Rx small label must provide the
established name and strength or
concentration of each active ingredient.
(4) Controlled substance symbol. For
controlled substances, this section of the
Rx small label must include the
required controlled substance symbol,
in accordance with part 1302 of this title
designating the schedule for the drug
substance.
(5) Prescription statement. This
section of the Rx small label must
include the following: ‘‘Rx Animal
Use’’.
(6) Target animals. This section of the
Rx small label must include the
statement: ‘‘For [target animal(s)] only’’.
(7) Full prescribing information
statement. This section of the Rx small
label must include one of two
statements. If full prescribing
information is provided on the package
insert, the following statement must be
used: ‘‘Read package insert for full
prescribing information.’’ If full
prescribing information is provided on
the secondary container labeling, the
following statement must be used:
‘‘Read package labeling for full
prescribing information.’’
(8) ‘‘Net Contents’’. This section of the
Rx small label must identify the
contents of the immediate container, in
accordance with § 201.51.
(9) Name and place of business. This
section of the Rx small label must
include the name and place of business
of the manufacturer, packer, or
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distributor, in accordance with section
502(b) of the Federal Food, Drug, and
Cosmetic Act.
(10) ‘‘Lot, Exp. and Storage’’ or ‘‘Lot
and Storage’’. This section of the Rx
small label must include the identifying
lot or control number of the Rx new
animal drug within the immediate
container. This section of the Rx small
label must also include the expiration
date of the Rx new animal drug within
the immediate container, in accordance
with § 201.17. Drug storage information
for the Rx new animal drug must also
be included in this section of the Rx
small label. In accordance with § 201.17,
if the immediate container provides a
single dose of the Rx new animal drug
and is packaged individually in a
secondary container that provides an
expiration date on the secondary
container labeling or secondary
container, an expiration date is not
required on the Rx small label or
immediate container. If an expiration
date is not provided on the Rx small
label or immediate container per this
provision, then this section of the Rx
small label must be entitled ‘‘Lot and
Storage.’’
(11) ‘‘Revision Date’’. This section of
the Rx small label must include the date
of the most recent revision of the Rx
small label, listing the month followed
by the year.
(d) Labeling for secondary containers
for Rx new animal drugs that include a
package insert (Rx secondary container
labeling). If a secondary container is
provided for an approved or
conditionally approved Rx new animal
drug and the Rx new animal drug
includes a package insert, the following
information, as applicable, must appear
in the order listed on the secondary
container labeling (Rx secondary
container labeling). In accordance with
section 201(k) of the Federal Food,
Drug, and Cosmetic Act, the Rx
secondary container labeling may
exclude any of the information
described in this subsection that is
required by paragraphs (b) or (c) of this
section to appear on the label if such
information is easily legible through the
Rx secondary container. Section
headings, subsection headings, and
other text presented in quotations in
this paragraph must appear verbatim on
the Rx secondary container labeling.
Sections and subsections are not
numbered on the Rx secondary
container labeling. For Rx secondary
container labeling with a front panel
and one side or back panel, the
information identified in paragraph
(d)(1) of this section must be provided
on the front panel in the order listed,
and the information identified in
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paragraph (d)(2) of this section must be
provided on the side or back panel in
the order listed. For Rx secondary
container labeling with a front panel
and multiple side and/or back panels,
the information identified in paragraph
(d)(1) must be provided on the Rx
secondary container labeling in the
order listed followed by the information
identified in paragraph (d)(2) in the
order listed, starting on the front panel,
continuing on the panel immediately to
the right of the front panel, and
continuing to fill the panels to the right
until all of the information is presented.
In all instances, the information
specified in paragraphs (d)(2)(v) and (vi)
of this section must appear on the same
panel.
(1) Front panel. The following
information must appear on the front
panel of the Rx secondary container
labeling in the order listed.
(i) Drug product identification. This
section of the Rx secondary container
labeling must include:
(A) The proprietary name of the
finished drug product;
(B) The established name of the drug
product;
(C) The route(s) of administration, if
not included as part of the established
name of the drug product;
(D) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(E) The established name and strength
or concentration of each active
ingredient;
(F) If applicable, a statement that the
product is sterile;
(G) The pharmacological class of the
new animal drug, if required to facilitate
the drug’s safe and effective use; and
(H) For controlled substances, the
required controlled substance symbol,
in accordance with part 1302 of this title
designating the schedule for the drug
substance.
(ii) Prescription statement. The
requirements of paragraph (a)(2) of this
section apply.
(iii) Conditional approval statement.
The requirements of paragraph (a)(3) of
this section apply.
(iv) Boxed warnings. The
requirements of paragraph (a)(4) of this
section apply.
(v) ‘‘Indications for Use’’. The
requirements of paragraph (a)(7) of this
section apply.
(vi) Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use as
listed under § 530.41 of this chapter, the
requirements of paragraph (a)(5) of this
section apply.
(vii) ‘‘Net Contents’’. This section of
the Rx secondary container labeling
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must identify the contents of the
secondary container.
(viii) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of paragraph
(a)(21) of this section apply.
(2) Side or back panel. The following
information must appear on the side or
back panel of the Rx secondary
container labeling in the order listed.
(i) Full prescribing information
statement. This section of the Rx
secondary container labeling must
include the following statement: ‘‘Before
using this drug, read package insert for
full prescribing information.’’
(ii) ‘‘Dosage and Administration’’.
The requirements of paragraph (a)(8) of
this section apply.
(iii) ‘‘Contraindications’’. The
requirements of paragraph (a)(9) of this
section apply.
(iv) ‘‘Warnings and Precautions’’. The
requirements of paragraph (a)(10) of this
section apply.
(v) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. The requirements of
paragraph (b)(2)(iii) of this section
apply.
(vi) ‘‘Inactive Ingredients’’. The
requirements of paragraph (a)(6)(viii) of
this section apply.
(vii) ‘‘Storage, Handling, and
Disposal’’. The requirements of
paragraph (a)(20) of this section apply.
(viii) Name and place of business.
The requirements of paragraph (a)(22) of
this section apply.
(ix) ‘‘Lot Number and Expiration
Date’’. This section of the Rx secondary
container labeling must include the
identifying lot or control number of the
Rx new animal drug within the
secondary container. This section of the
Rx secondary container labeling must
also include the expiration date of the
Rx new animal drug within the
secondary container, in accordance with
§ 201.17. Alternatively, this section
must refer to the location on the Rx
secondary container labeling or
secondary container where the lot or
control number and expiration date are
printed. In accordance with § 201.17, an
expiration date may be excluded from
the Rx secondary container labeling or
secondary container if the expiration
date provided on the Rx label, Rx small
label, or immediate container is easily
legible through the secondary container.
(x) ‘‘Revision Date’’. This section of
the Rx secondary container labeling
must include the date of the most recent
version of the Rx secondary container
labeling, listing the month followed by
the year.
(e) Shipping labeling for Rx new
animal drugs (Rx shipping labeling). If
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shipping labeling is provided for an
approved or conditionally approved Rx
new animal drug (Rx shipping labeling),
the following information, as applicable,
must appear in the order listed on the
Rx shipping labeling. Section headings
and other text presented in quotations
in this paragraph must appear verbatim
on the Rx shipping labeling. Sections
are not numbered on the Rx shipping
labeling.
(1) Proprietary name. This section of
the Rx shipping labeling must provide
the proprietary name of the finished
drug product, unless the Rx new animal
drug is a controlled substance.
(2) Established name. This section of
the Rx shipping labeling must provide
the established name of the drug
product, unless the Rx new animal drug
is a controlled substance.
(3) Active ingredient(s). This section
of the Rx shipping labeling must
provide the established name and
strength or concentration of each active
ingredient, unless the Rx new animal
drug is a controlled substance.
(4) Conditional approval statement.
The requirements of paragraph (a)(3) of
this section apply, unless the Rx new
animal drug is a controlled substance.
(5) ‘‘Net Contents’’. This section of the
Rx shipping labeling must identify the
contents of the shipping carton.
(6) ‘‘Storage and Handling’’. This
section of the Rx shipping labeling must
include drug storage information. If
required by FDA to facilitate the drug’s
safe and effective use, also include
handling information.
(7) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of paragraph
(a)(21) of this section apply, unless the
Rx new animal drug is a controlled
substance.
(8) Name and place of business. The
requirements of paragraph (a)(22) of this
section apply.
(9) ‘‘Lot Number and Expiration
Date’’. This section of the Rx shipping
labeling must include the identifying lot
or control number(s) and the expiration
date(s) of the Rx new animal drug
within the shipping carton.
(10) ‘‘Revision Date’’. This section of
the Rx shipping labeling must include
the date of the most recent revision of
the Rx shipping labeling, listing the
month followed by the year.
(f) Other approved labeling for Rx new
animal drugs (Rx other approved
labeling). If other approved labeling is
provided for an approved or
conditionally approved Rx new animal
drug (Rx other approved labeling), such
as labeling on display cartons and
multi-unit cartons (excluding shipping
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cartons), the following information, as
applicable, must appear in the order
listed on the Rx other approved
labeling. Section headings and other
text presented in quotations in this
paragraph must appear verbatim on the
Rx other approved labeling. Sections are
not numbered on the Rx other approved
labeling.
(1) Proprietary name. This section of
the Rx other approved labeling must
provide the proprietary name of the
finished drug product.
(2) Established Name. This section of
the Rx other approved labeling must
provide the established name of the
drug product.
(3) Active ingredient(s). This section
of the Rx other approved labeling must
provide the established name and
strength or concentration of each active
ingredient.
(4) Controlled substance symbol. For
controlled substances, this section of the
Rx other approved labeling must
include the required controlled
substance symbol, in accordance with
part 1302 of this title designating the
schedule for the drug substance.
(5) Prescription statement. The
requirements of paragraph (a)(2) of this
section apply.
(6) Conditional approval statement.
The requirements of paragraph (a)(3) of
this section apply.
(7) Boxed warnings. The requirements
of paragraph (a)(4) of this section apply.
(8) Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use as
listed under § 530.41 of this chapter, the
requirements of paragraph (a)(5) of this
section apply.
(9) ‘‘Net Contents’’. This section of the
Rx other approved labeling must
identify the contents of the container to
which the Rx other approved labeling
applies.
(10) ‘‘Storage, Handling, and
Disposal’’. The requirements of
paragraph (a)(20) of this section apply.
(11) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of paragraph
(a)(21) of this section apply.
(12) Name and place of business. The
requirements of paragraph (a)(22) of this
section apply.
(13) ‘‘Lot Number and Expiration
Date’’. This section of the Rx other
approved labeling must include the
identifying lot or control number of the
Rx new animal drug within the
container to which the Rx other
approved labeling applies. This section
of the Rx other approved labeling must
also include the expiration date of the
Rx new animal drug within the
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container to which the Rx other
approved labeling applies. In
accordance with § 201.17, an expiration
date may be excluded from the Rx other
approved labeling if the expiration date
provided on containers within or their
labeling is easily legible through the
container to which the Rx other
approved labeling applies.
(14) ‘‘Revision Date’’. This section of
the Rx other approved labeling must
include the date of the most recent
revision of the Rx other approved
labeling, listing the month followed by
the year.
§ 201.407 Content and format for over-thecounter (OTC) new animal drug labeling.
This section describes specific
content and format requirements for the
labeling of approved or conditionally
approved OTC new animal drugs other
than those for use in animal feeds that
are subject to part 558 of this chapter.
See § 201.409 for content and format
requirements for the labeling of
approved or conditionally approved
new animal drugs for use in animal
feeds that are subject to part 558 of this
chapter. Omit labeling sections or
subsections that do not apply to the
OTC new animal drug. The final content
of each applicable component and
section of labeling is determined by
FDA. In addition to the content and
format requirements in this section, the
labeling of approved or conditionally
approved OTC new animal drugs must
comply with other applicable
requirements in this subpart.
(a) Labeling providing full product
information. All approved or
conditionally approved OTC new
animal drugs must provide full product
information as described in this
paragraph. The package insert must
include full product information. If no
package insert is provided, the
secondary container labeling must
include full product information as
described in this paragraph. If neither a
package insert nor a secondary
container is provided, the label must
include full product information as
described in this paragraph. The
following information, as applicable,
must appear in the order listed on the
labeling component providing full
product information. If full product
information is provided on the
secondary container labeling, in
accordance with section 201(k) of the
Federal Food, Drug, and Cosmetic Act,
the secondary container labeling may
exclude any of the information
described in this subsection that is
required by paragraphs (b) or (c) of this
section to appear on the label if such
information is easily legible through the
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secondary container. Section headings,
subsection headings, and other text
presented in quotations in this
paragraph must appear verbatim on the
labeling providing full product
information. Sections and subsections
are not numbered on full product
information.
(1) Drug product identification. This
section of full product information must
include:
(i) The proprietary name of the
finished drug product;
(ii) The established name of the drug
product;
(iii) The route(s) of administration, if
not included as part of the established
name of the drug product;
(iv) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(v) The established name and strength
or concentration of each active
ingredient, except that the strength or
concentration may be excluded from
full product information provided on a
package insert that applies to multiple
strengths or concentrations; and
(vi) The pharmacological class of the
new animal drug, if required to facilitate
the drug’s safe and effective use.
(2) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(3) ‘‘Uses’’. Include the following
information in this section of full
product information in order:
(i) The approved or conditionally
approved indication(s) and target
animal(s) in the following format: ‘‘For
[indication(s)] in [target animal(s)]’’;
(ii) A statement indicating that the
new animal drug is approved or
conditionally approved for use only
under specific conditions, if applicable;
(iii) A statement describing the
relative effectiveness of doses within the
approved range of doses, if required by
FDA to facilitate the drug’s safe and
effective use; and
(iv) A statement(s) indicating animals
for which the new animal drug is not
approved or conditionally approved, if
FDA determines such a statement(s) is
required for safety and/or effectiveness
reasons.
(4) Extralabel use statement. This
section of full product information must
include the following extralabel use
statement: ‘‘It is a violation of Federal
law to use this drug product other than
as directed in the labeling or as directed
by your veterinarian.’’
(5) Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use as
listed under § 530.41 of this chapter, the
requirements of § 201.405(a)(5) apply.
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(6) ‘‘Description’’. This section of full
product information must include:
(i) The proprietary name of the
finished drug product;
(ii) The established name of the drug
product;
(iii) The route(s) of administration, if
not included as part of the established
name of the drug product;
(iv) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(v) A description of the identifying
characteristics of the dosage form, such
as color, shape, coating, scoring, and
imprinting;
(vi) The established name and
strength or concentration of each active
ingredient, including all available
strengths or concentrations to which full
product information applies;
(vii) If applicable, a statement that the
product is sterile; and
(viii) When inactive ingredients are
provided on full product information,
the requirements of § 201.405(a)(6)(viii)
apply.
(7) ‘‘Warnings’’. This section of full
product information is required for all
approved or conditionally approved
new animal drugs. Include in the
following order all applicable
subsections, headings, and information:
(i) ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods’’.
The requirements of § 201.405(a)(10)(i)
apply.
(ii) ‘‘User Safety Warnings’’. The
requirements of § 201.405(a)(10)(ii)
apply.
(iii) ‘‘Animal Safety Warnings’’. All
contraindications, target animal safety
warnings that identify any serious
adverse reaction or potential hazard to
the target animal(s) associated with the
use of the new animal drug, adverse
reactions, and post-approval adverse
drug experiences must be included in
this subsection of full product
information. These items must be listed
in decreasing order of severity or
frequency.
(iv) ‘‘Environmental Warnings’’. The
requirements of § 201.405(a)(10)(iv)
apply.
(v) ‘‘Other Warnings’’. The
requirements of § 201.405(a)(10)(v)
apply.
(8) ‘‘Additional Recommendations’’.
This section of full product information
must include all precautions.
(9) ‘‘Other Effects You May Notice’’.
This section of full product information
must include all statements required by
FDA that identify any effects of the OTC
new animal drug on the target animal(s)
that are not considered
contraindications, target animal safety
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warnings, adverse reactions, or postapproval adverse drug experiences.
(10) ‘‘Directions’’. This section of full
product information must include for
each indication and target animal:
(i) The route(s) of administration, and
specific site(s) of administration, if
applicable;
(ii) The dose (or dose range);
(iii) The intervals between doses, if
applicable;
(iv) The duration of treatment;
(v) The maximum volume per
injection site, if required to facilitate the
drug’s safe and effective use; and
(vi) Other information regarding
administration, if required by FDA to
facilitate the drug’s safe and effective
use.
(11) ‘‘Net Contents’’. This section of
full product information, when
presented on the label or the secondary
container labeling, must identify the
contents of the immediate container, in
accordance with § 201.62, or the
secondary container, respectively.
Exclude this section from package
inserts.
(12) ‘‘How Supplied’’. The
requirements of § 201.405(a)(19) apply.
(13) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(14) ‘‘Questions/Comments?’’. The
following statements must be included
in this section of full product
information: ‘‘Contact [insert name of
business] at [insert business telephone
number] or [insert business web
address]. To report side effects, contact
[insert name of business] at [insert
business telephone number]. For
additional information about reporting
side effects for animal drugs, contact
FDA at [insert current FDA telephone
number for voluntary reporting of
adverse drug experiences] or [insert
current FDA web address for voluntary
reporting of adverse drug experiences].’’
Use as the name of the business the
manufacturer, packer, or distributor
identified in the ‘‘Name and place of
business’’ section of full product
information according to paragraph
(a)(16) of this section. If more than one
business is identified in the ‘‘Name and
place of business’’ section of full
product information, select the most
appropriate to identify as the ‘‘business’’
in the ‘‘Questions/Comments?’’ section
of full product information to provide
additional information about the OTC
new animal drug and to contact
regarding suspected adverse drug
experiences.
(15) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
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drugs, the requirements of
§ 201.405(a)(21) apply.
(16) Name and place of business. The
requirements of § 201.405(a)(22) apply.
(17) ‘‘Lot Number and Expiration
Date’’. This section is required when
full product information is provided on
the secondary container labeling or the
label. This section must include the
identifying lot or control number of the
OTC new animal drug within the
secondary container or immediate
container. This section must also
include the expiration date of the OTC
new animal drug within the secondary
container or immediate container, in
accordance with § 201.17. Alternatively,
this section must refer to the location on
the secondary container labeling,
secondary container, label, or
immediate container where the lot or
control number and expiration date are
printed. If full product information is
provided on the secondary container
labeling, in accordance with § 201.17,
an expiration date may be excluded
from the secondary container labeling or
secondary container if the expiration
date provided on the label or immediate
container is easily legible through the
secondary container.
(18) ‘‘Revision Date’’. This section of
full product information must include
the date of the most recent revision of
the component of labeling that provides
full product information, listing the
month followed by the year.
(b) OTC new animal drug label not
providing full product information (OTC
label). All approved or conditionally
approved OTC new animal drugs must
provide a label. If a package insert or
secondary container labeling with full
product information is provided for an
approved or conditionally approved
OTC new animal drug and the label
does not provide full product
information in accordance with
paragraph (a) of this section, the
following information, as applicable,
must appear in the order listed on the
label for approved or conditionally
approved OTC new animal drugs (OTC
label). If there is insufficient space on
the immediate container for a label to
provide for all of the following
information, then an OTC small label is
required instead. The requirements for
an OTC small label are provided in
paragraph (c) of this section. Section
headings and other text presented in
quotations in this paragraph must
appear verbatim on the OTC label.
Sections are not numbered on the OTC
label. For OTC labels with a front panel
and one side or back panel, the
information identified in paragraph
(b)(1) of this section must be provided
on the front panel in the order listed,
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and the information identified in
paragraph (b)(2) of this section must be
provided on the side or back panel in
the order listed. If the OTC label
consists of a single panel, the
information identified in paragraph
(b)(1) of this section must be provided
on the OTC label in the order listed
followed by the information identified
in paragraph (b)(2) in the order listed.
For OTC labels with a front panel and
multiple side and/or back panels, the
information identified in paragraph
(b)(1) must be provided on the OTC
label in the order listed followed by the
information identified in paragraph
(b)(2) in the order listed, starting on the
front panel, continuing on the panel
immediately to the right of the front
panel, and continuing to fill the panels
to the right until all of the information
is presented. In all instances, the
information specified in paragraphs
(b)(2)(iii) and (iv) of this section must
appear on the same panel.
(1) Front panel. The following
information must appear on the front
panel of the OTC label in the order
listed.
(i) Drug product identification. This
section of the OTC label must include:
(A) The proprietary name of the
finished drug product;
(B) The established name of the drug
product;
(C) The route(s) of administration, if
not included as part of the established
name of the drug product;
(D) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(E) The established name and strength
or concentration of each active
ingredient;
(F) If applicable, a statement that the
product is sterile; and
(G) The pharmacological class of the
new animal drug, if required to facilitate
the drug’s safe and effective use.
(ii) Conditional approval statement.
For conditionally approved new animal
drugs, the requirements of
§ 201.405(a)(3) apply.
(iii) ‘‘Uses’’. The requirements of
paragraph (a)(3) of this section apply.
However, if there is insufficient space
on the OTC label for the complete
‘‘Uses’’ section as specified in paragraph
(a)(3), then include the statement
required in paragraph (a)(3)(i) or, if
there is insufficient space on the OTC
label for the statement in paragraph
(a)(3)(i), then include the statement,
‘‘For [abbreviated indication(s)] in
[target animal(s)]’’). In either situation
where there is insufficient space on the
OTC label for the complete ‘‘Uses’’
section as specified in paragraph (a)(3),
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the required statement must be followed
by, ‘‘See package insert for complete
‘Uses’ ’’ if full product information is
provided on a package insert, or ‘‘See
package labeling for complete ‘Uses’ ’’ if
full product information is provided on
the secondary container labeling.
(iv) Extralabel use statement. The
requirements of paragraph (a)(4) of this
section apply.
(v) Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use as
listed under § 530.41 of this chapter, the
requirements of § 201.405(a)(5) apply.
(vi) ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods’’.
For new animal drugs approved or
conditionally approved for use in foodproducing animals, the requirements of
§ 201.405(a)(10)(i) apply. If there is
insufficient space on the front panel of
OTC labels consisting of only a front
panel and one side or back panel for the
information required in
§ 201.405(a)(10)(i), this section must be
provided on the side or back panel of
the OTC label immediately following
the complete product information
statement specified in paragraph
(b)(2)(i) of this section.
(vii) ‘‘Net Contents’’. This section of
the OTC label must identify the contents
of the immediate container, in
accordance with § 201.62.
(viii) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of
§ 201.405(a)(21) apply.
(2) Side or back panel. The following
information must appear on the side or
back panel of the OTC label in the order
listed.
(i) Complete product information
statement. This section of the OTC label
must include one of two statements. If
full product information is provided on
the package insert, the following
statement must be used: ‘‘Before using
this drug, read package insert for
complete product information.’’ If full
product information is provided on the
secondary container labeling, the
following statement must be used:
‘‘Before using this drug, read package
labeling for complete product
information.’’
(ii) ‘‘Directions’’. The requirements of
paragraph (a)(10) of this section apply.
If there is insufficient space on the OTC
label for complete requirements as
specified in paragraph (a)(10) of this
section or if it is necessary for
additional information provided in full
product information that is not provided
on the OTC label to be read before
administering the drug, FDA may allow
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this section to be excluded from the
OTC label.
(iii) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the OTC
label must provide the established name
and strength or concentration of each
active ingredient. If the OTC new
animal drug contains one active
ingredient, this section of the OTC label
must be entitled ‘‘Active Ingredient’’. If
the OTC new animal drug contains more
than one active ingredient, this section
of the OTC label must be entitled
‘‘Active Ingredients.’’
(iv) ‘‘Inactive Ingredients’’. When
inactive ingredients are provided on the
OTC label, the requirements of
§ 201.405(a)(6)(viii) apply.
(v) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(vi) Name and place of business. This
section of the OTC label must include
the name and place of business of the
manufacturer, packer, or distributor, in
accordance with section 502(b) of the
Federal Food, Drug, and Cosmetic Act.
(vii) ‘‘Lot Number and Expiration
Date’’ or ‘‘Lot Number’’. This section of
the OTC label must include the
identifying lot or control number of the
OTC new animal drug within the
immediate container. This section of the
OTC label must also include the
expiration date of the OTC new animal
drug within the immediate container, in
accordance with § 201.17. Alternatively,
this section must refer to the location on
the OTC label or immediate container
where the lot or control number and
expiration date are printed. In
accordance with § 201.17, if the
immediate container provides a single
dose of the OTC new animal drug and
is packaged individually in a secondary
container that provides an expiration
date on the secondary container labeling
or secondary container, an expiration
date is not required on the OTC label or
immediate container. If an expiration
date is not provided on the OTC label
or immediate container per this
provision, then this section of the OTC
label must be titled ‘‘Lot Number.’’
(viii) ‘‘Revision Date’’. This section of
the OTC label must include the date of
the most recent revision of the OTC
label, listing the month followed by the
year.
(c) OTC new animal drug small label
(OTC small label). The following
information must appear in the order
listed on the OTC small label. FDA will
make the final determination as to
whether an immediate container lacks
sufficient space for the label to include
all of the information required by
paragraph (b) of this section, taking into
consideration readability and legibility
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of the information. Section headings
and other text presented in quotations
in this paragraph must appear verbatim
on the OTC small label. Sections are not
numbered on the OTC small label.
(1) Proprietary name. This section of
the OTC small label must provide the
proprietary name of the finished drug
product.
(2) Established name. This section of
the OTC small label must provide the
established name of the drug product.
(3) Active ingredient(s). This section
of the OTC small label must provide the
established name and strength or
concentration of each active ingredient.
(4) Target animals. This section of the
OTC small label must include the
statement: ‘‘For [target animal(s)] only.’’
(5) Complete product information
statement. This section of the OTC
small label must include one of two
statements. If full product information is
provided on the package insert, the
following statement must be used:
‘‘Read package insert for complete
product information.’’ If full product
information is provided on the
secondary container labeling, the
following statement must be used:
‘‘Read package labeling for complete
product information.’’
(6) ‘‘Net Contents’’. This section of the
OTC small label must identify the
contents of the immediate container, in
accordance with § 201.62.
(7) Name and place of business. This
section of the OTC small label must
include the name and place of business
of the manufacturer, packer, or
distributor, in accordance with section
502(b) of the Federal Food, Drug, and
Cosmetic Act.
(8) ‘‘Lot, Exp. and Storage’’ or ‘‘Lot
and Storage’’. This section of the OTC
small label must include the identifying
lot or control number of the OTC new
animal drug within the immediate
container. This section of the OTC small
label must also include the expiration
date of the OTC new animal drugs
within the immediate container, in
accordance with § 201.17. Drug storage
information for the OTC new animal
drug must also be included in this
section of the OTC small label. In
accordance with § 201.17, if the
immediate container provides a single
dose of the OTC new animal drug and
is packaged individually in a secondary
container that provides an expiration
date on the secondary container labeling
or secondary container, an expiration
date is not required on the OTC small
label or immediate container. If an
expiration date is not provided on the
OTC small label or immediate container
per this provision, then this section of
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the OTC small label must be entitled
‘‘Lot and Storage.’’
(9) ‘‘Revision Date’’. This section of
the OTC small label must include the
date of the most recent revision of the
OTC small label, listing the month
followed by the year.
(d) Labeling for secondary containers
for OTC new animal drugs that include
a package insert (OTC secondary
container labeling). If a secondary
container is provided for an approved or
conditionally approved OTC new
animal drug and the OTC new animal
drug includes a package insert, the
following information, as applicable,
must appear in the order listed on the
secondary container labeling (OTC
secondary container labeling). In
accordance with section 201(k) of the
Federal Food, Drug, and Cosmetic Act,
the OTC secondary container labeling
may exclude any of the information
described in this subsection that is
required by paragraphs (b) or (c) of this
section to appear on the label if such
information is easily legible through the
OTC secondary container. Section
headings, subsection headings, and
other text presented in quotations in
this paragraph must appear verbatim on
the OTC secondary container labeling.
Sections and subsections are not
numbered on the OTC secondary
container labeling. For OTC secondary
container labeling with a front panel
and one side or back panel, the
information identified in paragraph
(d)(1) of this section must be provided
on the front panel in the order listed,
and the information identified in
paragraph (d)(2) of this section must be
provided on the side or back panel in
the order listed. For OTC secondary
container labeling with a front panel
and multiple side and/or back panels,
the information identified in paragraph
(d)(1) of this section must be provided
on the OTC secondary container
labeling in the order listed followed by
the information identified in paragraph
(d)(2) of this section in the order listed,
starting on the front panel, continuing
on the panel immediately to the right of
the front panel, and continuing to fill
the panels to the right until all of the
information is presented. In all
instances, the information specified in
paragraphs (d)(2)(iv) and (v) of this
section must appear on the same panel.
(1) Front panel. The following
information must appear on the front
panel of the OTC secondary container
labeling in the order listed.
(i) Drug product identification. This
section of the OTC secondary container
labeling must include:
(A) The proprietary name of the
finished drug product;
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(B) The established name of the drug
product;
(C) The route(s) of administration, if
not included as part of the established
name of the drug product;
(D) The dosage form of the finished
drug product, if not included as part of
the established name of the drug
product;
(E) The established name and strength
or concentration of each active
ingredient;
(F) If applicable, a statement that the
product is sterile; and
(G) The pharmacological class of the
new animal drug, if required to facilitate
the drug’s safe and effective use.
(ii) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(iii) ‘‘Uses’’. The requirements of
paragraph (a)(3) of this section apply.
(iv) Extralabel use statement. The
requirements of paragraph (a)(4) of this
section apply.
(v) Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use as
listed under § 530.41 of this chapter, the
requirements of § 201.405(a)(5) apply.
(vi) ‘‘Net Contents’’. This section of
the OTC secondary container labeling
must identify the contents of the
secondary container.
(vii) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of
§ 201.405(a)(21) apply.
(2) Side or back panel. The following
information must appear on the side or
back panel of the OTC secondary
container labeling in the order listed.
(i) Complete product information
statement. This section of the OTC
secondary container labeling must
include the following statement: ‘‘Before
using this drug, read package insert for
complete product information.’’
(ii) ‘‘Directions’’. The requirements of
paragraph (a)(10) of this section apply.
(iii) ‘‘Warnings’’. The requirements of
paragraph (a)(7) of this section apply.
(iv) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. The requirements of
paragraph (b)(2)(iii) of this section
apply.
(v) ‘‘Inactive Ingredients’’. When
inactive ingredients are provided on the
OTC secondary container labeling, the
requirements of § 201.405(a)(6)(viii)
apply.
(vi) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(vii) Name and place of business. The
requirements of § 201.405(a)(22) apply.
(viii) ‘‘Lot Number and Expiration
Date’’. This section of the OTC
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secondary container labeling must
include the identifying lot or control
number of the OTC new animal drug
within the secondary container. This
section of the OTC secondary container
labeling must also include the
expiration date of the OTC new animal
drug within the secondary container, in
accordance with § 201.17. Alternatively,
this section must refer to the location on
the OTC secondary container labeling or
secondary container where the lot or
control number and expiration date are
printed. In accordance with § 201.17, an
expiration date may be excluded from
the OTC secondary container labeling or
secondary container if the expiration
date provided on the OTC label, OTC
small label, or immediate container is
easily legible through the secondary
container.
(ix) ‘‘Revision Date’’. This section of
the OTC secondary container labeling
must include the date of the most recent
revision of the OTC secondary container
labeling, listing the month followed by
the year.
(e) Shipping labeling for OTC new
animal drugs (OTC shipping labeling). If
shipping labeling is provided for an
approved or conditionally approved
OTC new animal drug (OTC shipping
labeling), the following information, as
applicable, must appear in the order
listed on the OTC shipping labeling.
Section headings and other text
presented in quotations in this
paragraph must appear verbatim on the
OTC shipping labeling. Sections are not
numbered on the OTC shipping
labeling.
(1) Proprietary name. This section of
the OTC shipping labeling must provide
the proprietary name of the finished
drug product.
(2) Established name. This section of
the OTC shipping labeling must provide
the established name of the drug
product.
(3) Active ingredient(s). This section
of the OTC shipping labeling must
provide the established name and
strength or concentration of each active
ingredient.
(4) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(5) ‘‘Net Contents’’. This section of the
OTC shipping labeling must identify the
contents of the shipping carton.
(6) ‘‘Storage and Handling’’. This
section of the OTC shipping labeling
must include drug storage information.
If required by FDA to facilitate the
drug’s safe and effective use, also
include handling information.
(7) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
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drugs, the requirements of
§ 201.405(a)(21) apply.
(8) Name and place of business. The
requirements of § 201.405(a)(22) apply.
(9) ‘‘Lot Number and Expiration
Date’’. This section of the OTC shipping
labeling must include the identifying lot
or control number(s) and the expiration
date(s) of the OTC new animal drug
within the shipping carton.
(10) ‘‘Revision Date’’. This section of
the OTC shipping labeling must include
the date of the most recent revision of
OTC shipping labeling, listing the
month followed by the year.
(f) Other approved labeling for OTC
new animal drugs (OTC other approved
labeling). If other approved labeling is
provided for an approved or
conditionally approved OTC new
animal drug (OTC other approved
labeling), such as labeling on display
cartons and multi-unit cartons
(excluding shipping cartons), the
following information, as applicable,
must appear in the order listed on the
OTC other approved labeling. Section
headings and other text presented in
quotations in this paragraph must
appear verbatim on the OTC other
approved labeling. Sections are not
numbered on the OTC other approved
labeling.
(1) Proprietary name. This section of
the OTC other approved labeling must
provide the proprietary name of the
finished drug product.
(2) Established name. This section of
the OTC other approved labeling must
provide the established name of the
drug product.
(3) Active ingredient(s). This section
of the OTC other approved labeling
must provide the established name and
strength or concentration of each active
ingredient.
(4) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(5) Extralabel use statement. The
requirements of paragraph (a)(4) of this
section apply.
(6) Extralabel use prohibition
statement. For approved new animal
drugs prohibited from extralabel use as
listed under § 530.41 of this chapter, the
requirements of § 201.405(a)(5) apply.
(7) ‘‘Net Contents’’. This section of the
OTC other approved labeling must
identify the contents of the container to
which the OTC other approved labeling
applies.
(8) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(9) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
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drugs, the requirements of
§ 201.405(a)(21) apply.
(10) Name and place of business. The
requirements of § 201.405(a)(22) apply.
(11) ‘‘Lot Number and Expiration
Date’’. This section of the OTC other
approved labeling must include the
identifying lot or control number of the
OTC new animal drug within the
container to which the OTC other
approved labeling applies. This section
of the OTC other approved labeling
must also include the expiration date of
the OTC new animal drug within the
container to which the OTC other
approved labeling applies. In
accordance with § 201.17, an expiration
date may be excluded from the OTC
other approved labeling if the expiration
date on containers within or their
labeling is easily legible through the
container to which the OTC other
approved labeling applies.
(12) ‘‘Revision Date’’. This section of
the OTC other approved labeling must
include the date of the most recent
revision of the OTC other approved
labeling, listing the month followed by
the year.
§ 201.409 Content and format of labeling
for new animal drugs for use in animal
feeds.
This section describes specific
content and format requirements for the
labeling of approved or conditionally
approved new animal drugs for use in
animal feeds and that are subject to part
558 of this chapter, including VFD
drugs. Omit labeling sections or
subsections that do not apply to the new
animal drug for use in animal feeds. The
final content of each applicable
component and section of labeling is
determined by FDA. In addition to the
content and format requirements in this
section, the labeling of approved or
conditionally approved new animal
drugs for use in animal feeds and that
are subject to part 558 of this chapter
must comply with other applicable
requirements in this subpart.
(a) Type A medicated article label. All
approved or conditionally approved
Type A medicated articles must provide
a Type A medicated article label as
described in this paragraph. The
following information, as applicable,
must appear in the order listed on the
Type A medicated article label. Section
headings, subsection headings, and
other text presented in quotations in
this paragraph must appear verbatim on
the Type A medicated article label.
Sections and subsections are not
numbered on the Type A medicated
article label.
(1) Type A medicated article
identification. This section of the Type
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A medicated article label must include
in order:
(i) The proprietary name of the Type
A medicated article;
(ii) The established name of the Type
A medicated article; and
(iii) The phrase ‘‘Type A medicated
article’’ or ‘‘Type A liquid medicated
article,’’ as applicable, if not included as
part of the established name of the Type
A medicated article.
(2) VFD cautionary statement. For
VFD drugs, this section of the Type A
medicated article label must
prominently and conspicuously display
the cautionary statement, in accordance
with § 558.6(a)(6) of this chapter.
(3) Manufacturing statement. This
section of the Type A medicated article
label must include the statement: ‘‘For
further manufacturing only.’’
(4) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(5) ‘‘Indications for Use’’. The
requirements of § 201.407(a)(3) apply.
(6) Extralabel use statement. This
section of the Type A medicated article
label must include the following
extralabel use statement: ‘‘It is a
violation of Federal law to use other
than as directed in the labeling.’’
(7) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the Type A
medicated article label must provide the
established name and concentration of
each active ingredient in the Type A
medicated article. If the Type A
medicated article contains one active
ingredient, this section of the Type A
medicated article label must be entitled
‘‘Active Ingredient.’’ If the Type A
medicated article contains more than
one active ingredient, this section of the
Type A medicated article label must be
entitled ‘‘Active Ingredients.’’
(8) ‘‘Inactive Ingredients’’. When
inactive ingredients are provided on the
Type A medicated article label, the
requirements of § 201.405(a)(6)(viii)
apply.
(9) ‘‘Directions’’. This section of the
Type A medicated article label must
include the following three subsections
in order:
(i) ‘‘Approved Concentration(s) of
[Active Ingredient or Active Moiety] in
Type C Medicated Feeds’’. This
subsection of the Type A medicated
article label must provide the approved
concentration(s) of each active
ingredient in Type C medicated feeds to
be manufactured from the Type A
medicated article for each approved or
conditionally approved indications for
use. If an active ingredient is a salt or
other noncovalent derivative and its
concentration(s) in paragraph (a)(7) of
this section is expressed based on the
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active moiety, the approved
concentration(s) in the Type C
medicated feeds must be expressed
based on the active moiety, and the title
of this subsection must include the
name of the active moiety instead of the
active ingredient.
(ii) ‘‘Mixing Directions’’. This
subsection of the Type A medicated
article label must provide the approved
mixing directions for the manufacture of
approved medicated feeds from this
Type A medicated article for each
approved or conditionally approved
indications for use, including an
intermediate mixing step (i.e., preblend
step) if required.
(iii) ‘‘Feeding Directions’’. This
subsection of the Type A medicated
article label must provide the approved
feeding directions for each approved or
conditionally approved indications for
use for Type C medicated feeds
manufactured from this Type A
medicated article.
(10) ‘‘Warnings’’. This section of the
Type A medicated article label is
required for all Type A medicated
articles. Include in the following order
all applicable subsections, headings,
and information:
(i) ‘‘Withdrawal Periods and Residue
Warnings’’ or ‘‘Withdrawal Periods’’.
The requirements of § 201.405(a)(10)(i)
apply.
(ii) ‘‘User Safety Warnings’’. The
requirements of § 201.405(a)(10)(ii)
apply.
(iii) ‘‘Animal Safety Warnings’’. The
requirements of § 201.407(a)(7)(iii)
apply.
(iv) ‘‘Environmental Warnings’’. The
requirements of § 201.405(a)(10)(iv)
apply.
(v) ‘‘Other Warnings’’. The
requirements of § 201.405(a)(10)(v)
apply.
(11) ‘‘Additional Recommendations’’.
The requirements of § 201.407(a)(8)
apply.
(12) ‘‘Other Effects You May Notice’’.
The requirements of § 201.407(a)(9)
apply.
(13) ‘‘Net Weight’’. This section of the
Type A medicated article label must list
the net weight of the Type A medicated
article in the immediate container.
(14) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(15) ‘‘Questions/Comments?’’. The
following statements must be included
in this section of the Type A medicated
article label: ‘‘Contact [insert name of
business] at [insert business telephone
number] or [insert business web
address]. To report side effects, contact
[insert name of business] at [insert
business telephone number]. For
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additional information about reporting
side effects for animal drugs, contact
FDA at [insert current FDA telephone
number for voluntary reporting of
adverse drug experiences] or [insert
current FDA web address for voluntary
reporting of adverse drug experiences].’’
Use as the name of the business the
manufacturer, packer, or distributor
identified in the ‘‘Name and place of
business’’ section of the Type A
medicated article label according to
paragraph (a)(17) of this section. If more
than one business is identified in the
‘‘Name and place of business’’ section of
the Type A medicated article label,
select the most appropriate to identify
as the ‘‘business’’ in the ‘‘Questions/
Comments?’’ section of the Type A
medicated article label to provide
additional information about the Type A
medicated article and to contact
regarding suspected adverse drug
experiences.
(16) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of
§ 201.405(a)(21) apply.
(17) Name and place of business. The
requirements of § 201.405(a)(22) apply.
(18) ‘‘Lot Number and Expiration
Date’’. This section of the Type A
medicated article label must include the
identifying lot or control number of the
Type A medicated article within the
immediate container. In accordance
with § 226.58(d) of this chapter, this
section of the Type A medicated article
label must also include the expiration
date of the Type A medicated article
within the immediate container.
Alternatively, this section must refer to
the location on the Type A medicated
article label or immediate container
where the lot or control number and
expiration date are printed.
(19) ‘‘Revision Date’’. This section of
the Type A medicated article label must
include the date of the most recent
revision of the Type A medicated article
label, listing the month followed by the
year.
(b) Representative Type B medicated
feed labeling. The following
information, as applicable, must appear
in the order listed on the representative
Type B medicated feed labeling. Section
headings, subsection headings, and
other text presented in quotations in
this paragraph must appear verbatim on
the representative Type B medicated
feed labeling. Sections and subsections
are not numbered on the representative
Type B medicated feed labeling.
(1) Description of the Type B
medicated feed. This section of the
representative Type B medicated feed
labeling serves as a placeholder for the
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proprietary name to be added by the
feed manufacturer to the label of the
final Type B medicated feed
manufactured in accordance with the
approved representative Type B
labeling. The description of the Type B
medicated feed must:
(i) Distinguish the Type B medicated
feed from any other Type B medicated
feeds approved or conditionally
approved within the same application;
and
(ii) Not include the proprietary name
of a Type A medicated article.
(2) Established name of the Type B
medicated feed. The established name
of the Type B medicated feed must
include in the following order:
(i) The active moiety or active
ingredient of each new animal drug, as
determined by FDA; and
(ii) One of the following statements,
as applicable: ‘‘Type B medicated feed’’
or ‘‘Type B liquid medicated feed’’.
(3) VFD cautionary statement. The
requirements of paragraph (a)(2) of this
section apply.
(4) Undiluted statement. This section
of the representative Type B medicated
feed labeling must include the
statement: ‘‘Do Not Feed Undiluted.’’
(5) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(6) ‘‘Indications for Use’’. The
requirements of § 201.407(a)(3) apply.
Include only the approved or
conditionally approved indications for
use for the specific Type B medicated
feed to which the representative Type B
medicated feed labeling applies.
(7) Extralabel use statement. The
requirements of paragraph (a)(6) of this
section apply.
(8) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the
representative Type B medicated feed
labeling must include the following
information for the specific Type B
medicated feed to which the
representative Type B medicated feed
labeling applies. If the Type B
medicated feed contains one active
ingredient, this section of the
representative Type B medicated feed
labeling must be entitled ‘‘Active
Ingredient.’’ If the Type B medicated
feed contains more than one active
ingredient, this section of the
representative Type B medicated feed
labeling must be entitled ‘‘Active
Ingredients.’’
(i) The established name of each
active ingredient; and
(ii) The concentration or range of
concentrations of each active ingredient
as approved by FDA. If included as a
range, the active ingredient
concentrations must reference a footnote
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at the bottom of this page of the
representative Type B labeling
indicating that each final printed Type
B medicated feed label must only
include a single concentration of each
active ingredient.
(9) ‘‘Guaranteed Analysis’’. This
section of the representative Type B
medicated feed labeling must provide
for the nutritional content guarantees of
the Type B medicated feed appropriate
for the target animal(s) in addition to
any other required specifications.
(10) ‘‘Ingredients’’. This section of the
representative Type B medicated feed
labeling must include the following:
(i) A statement that feed ingredients
must be listed on each final printed
Type B medicated feed label by their
common or usual names in descending
order of predominance by weight, in
accordance with § 501.4(a) of this
chapter, including their collective
names where permitted, in accordance
with § 501.4(b)(13) of this chapter; and
(ii) A statement that spices, flavorings,
colorings, and chemical preservatives, if
used, must be declared on each final
printed Type B medicated feed label, in
accordance with § 501.22 of this
chapter.
(11) ‘‘Mixing Directions’’. This section
of the representative Type B medicated
feed labeling must provide the approved
mixing directions for the manufacture of
a Type C medicated feed(s) or another
Type B medicated feed(s), as applicable,
from the Type B medicated feed for
which the representative Type B
medicated feed labeling applies.
(12) ‘‘Warnings’’. The requirements of
paragraph (a)(10) of this section apply.
Include only the warnings for the
specific Type B medicated feed to
which the representative Type B
medicated feed labeling applies.
(13) ‘‘Additional Recommendations’’.
The requirements of § 201.407(a)(8)
apply. Include only the precautions for
the specific Type B medicated feed to
which the representative Type B
medicated feed labeling applies.
(14) ‘‘Other Effects You May Notice’’.
The requirements of § 201.407(a)(9)
apply. Include only statements of other
effects for the specific Type B medicated
feed to which the representative Type B
medicated feed labeling applies.
(15) Name and place of business. This
section of the representative Type B
medicated feed labeling must provide
for the name and place of business of
the manufacturer, packer, or distributor
of the final Type B medicated feed, in
accordance with § 501.5 of this chapter.
(16) ‘‘Net Weight’’. This section of the
representative Type B medicated feed
labeling must provide for the statement
on the final printed Type B medicated
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feed label of the net weight of the Type
B medicated feed in the immediate
container.
(17) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(18) ‘‘Questions/Comments?’’. The
following statements must be included
in this section of the representative
Type B medicated feed labeling:
‘‘Contact [name of business] at [business
telephone number] or [business web
address]. For additional information
about reporting problems with
medicated feeds, contact FDA at [insert
current FDA telephone number for
voluntary reporting of adverse drug
experiences] or [insert current FDA web
address for voluntary reporting of
adverse drug experiences].’’ The
information in the bracketed areas of the
first statement are placeholders for the
business of the manufacturer, packer, or
distributor of the final Type B
medicated feed to insert their name and
contact information. The information in
the bracketed areas of the second
statement must be inserted by the
sponsor of the new animal drug
application.
(19) ‘‘Lot, Batch, or Control Number’’.
This section of the representative Type
B medicated feed labeling must provide
for an identifying lot, batch, or control
number on the final printed Type B
medicated feed label.
(20) ‘‘Expiration Date’’. If an
expiration date is required, in
accordance with § 514.1(b)(5)(x) of this
chapter, then this section of the
representative Type B medicated feed
labeling must provide for the expiration
date to be printed on the final printed
Type B medicated feed label. The
approved expiration period must also be
included in this section of the
representative Type B medicated feed
labeling.
(21) ‘‘Revision Date’’. This section of
the representative Type B medicated
feed labeling must include the date of
the most recent revision of the
representative Type B medicated feed
labeling, listing the month followed by
the year.
(c) Representative Type C medicated
feed labeling. The following
information, as applicable, must appear
in the order listed on the representative
Type C medicated feed labeling. Section
headings, subsection headings, and
other text presented in quotations in
this paragraph must appear verbatim on
the representative Type C medicated
feed labeling. Sections and subsections
are not numbered on the representative
Type C medicated feed labeling.
(1) Description of the Type C
medicated feed. This section of the
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representative Type C medicated feed
labeling serves as a placeholder for the
proprietary name to be added by the
feed manufacturer to the label of the
final Type C medicated feed
manufactured in accordance with the
approved representative Type C
medicated feed labeling. The
description of the Type C medicated
feeds must:
(i) Distinguish the Type C medicated
feed from any other Type C medicated
feeds approved or conditionally
approved within the same application;
and
(ii) Not include the proprietary name
of a Type A medicated article.
(2) Established name of the Type C
medicated feed. The established name
of the Type C medicated feed must
include in the following order:
(i) The active moiety or active
ingredient of each new animal drug, as
determined by FDA; and
(ii) One of the following statements,
as applicable: ‘‘Type C medicated feed,’’
‘‘Type C liquid medicated feed,’’ ‘‘Type
C top-dress medicated feed,’’ ‘‘Type C
free-choice medicated feed,’’ or ‘‘Type C
liquid free-choice medicated feed’’.
(3) VFD cautionary statement. The
requirements of paragraph (a)(2) of this
section apply.
(4) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(5) ‘‘Indications for Use’’. The
requirements of § 201.407(a)(3) apply.
Include only the approved or
conditionally approved indications for
use for the specific Type C medicated
feed to which the representative Type C
medicated feed labeling applies.
(6) Extralabel use statement. The
requirements of paragraph (a)(6) of this
section apply.
(7) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the
representative Type C medicated feed
labeling must include the following
information for the specific Type C
medicated feed to which the
representative Type C medicated feed
labeling applies. If the Type C
medicated feed contains one active
ingredient, this section of the
representative Type C medicated feed
labeling must be entitled ‘‘Active
Ingredient.’’ If the Type C medicated
feed contains more than one active
ingredient, this section of the
representative Type C medicated feed
labeling must be entitled ‘‘Active
Ingredients.’’
(i) The established name of each
active ingredient; and
(ii) The concentration or range of
concentrations of each active ingredient
as approved by FDA. If included as a
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range, the active ingredient
concentrations must reference a footnote
at the bottom of this page of the
representative Type C medicated feed
labeling indicating that each final
printed Type C medicated feed label
must only include a single
concentration of each active ingredient.
(8) ‘‘Guaranteed Analysis’’. The
requirements of paragraph (b)(9) of this
section apply.
(9) ‘‘Ingredients’’. This section of the
representative Type C medicated feed
labeling must include the following:
(i) For Type C medicated feeds that
are not Type C free-choice medicated
feeds:
(A) A statement that feed ingredients
must be listed on each final printed
Type C medicated feed label by their
common or usual names in descending
order of predominance by weight, in
accordance with § 501.4(a) of this
chapter, including their collective
names where permitted, in accordance
with § 501.4(b)(13) of this chapter; and
(B) A statement that spices, flavorings,
colorings, and chemical preservatives, if
used, must be declared on each final
printed Type C medicated feed label, in
accordance with § 501.22 of this
chapter.
(ii) For Type C free-choice medicated
feeds, a list of the feed ingredients and
their inclusion rates, including the drug
concentrations exactly as they appear in
the approved non-proprietary formula
published for the specific new animal
drug in part 558 of this chapter.
(10) ‘‘Feeding Directions’’. The
requirements of paragraph (a)(9)(iii) of
this section apply. This section of the
representative Type C medicated feed
labeling must include the approved
feeding directions for the specific Type
C medicated feed for which the
representative Type C medicated feed
labeling applies.
(11) ‘‘Warnings’’. The requirements of
paragraph (a)(10) of this section apply.
Include only the warnings for the
specific Type C medicated feed to
which the representative Type C
medicated feed labeling applies.
(12) ‘‘Additional Recommendations’’.
The requirements of § 201.407(a)(8)
apply. Include only the precautions for
the specific Type C medicated feed to
which the representative Type C
medicated feed labeling applies.
(13) ‘‘Other Effects You May Notice’’.
The requirements of § 201.407(a)(9)
apply. Include only statements of other
effects for the specific Type C medicated
feed to which the representative Type C
medicated feed labeling applies.
(14) Name and place of business. This
section of the representative Type C
medicated feed labeling must provide
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for the name and place of business of
the manufacturer, packer, or distributor
of the final Type C medicated feed, in
accordance with § 501.5 of this chapter.
(15) ‘‘Net Weight’’. This section of the
representative Type C medicated feed
labeling must provide for the statement
of net weight on the final printed Type
C medicated feed label of the Type C
medicated feed in the immediate
container.
(16) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(17) ‘‘Questions/Comments?’’. The
following statements must be included
in this section of the representative
Type C medicated feed labeling:
‘‘Contact [name of business] at [business
telephone number] or [business web
address]. For additional information
about reporting side effects or other
problems with medicated feeds, contact
FDA at [insert current FDA telephone
number for voluntary reporting of
adverse drug experiences] or [insert
current FDA web address for voluntary
reporting of adverse drug experiences].’’
The information in the bracketed areas
of the first statement are placeholders
for the business of the manufacturer,
packer, or distributor of the final Type
C medicated feed to insert their name
and contact information. The
information in the bracketed areas of the
second statement must be inserted by
the sponsor of the new animal drug
application.
(18) ‘‘Lot, Batch, or Control Number’’.
This section of the representative Type
C medicated feed labeling must provide
for an identifying lot, batch, or control
number on the final printed Type C
medicated feed label.
(19) ‘‘Expiration Date’’. If an
expiration date is required, in
accordance with § 514.1(b)(5)(x) of this
chapter, then this section of the
representative Type C medicated feed
labeling must provide for the expiration
date to be printed on the final printed
Type C medicated feed label. The
approved expiration period must also be
included in this section of the
representative Type C medicated feed
labeling.
(20) ‘‘Revision Date’’. This section of
representative Type C medicated feed
labeling must include the date of the
most recent revision of the
representative Type C medicated feed
labeling, listing the month followed by
the year.
(d) Proprietary Type B medicated feed
label. The following information, as
applicable, must appear in the order
listed on the proprietary Type B
medicated feed label. Section headings,
subsection headings, and other text
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presented in quotations in this
paragraph must appear verbatim on the
proprietary Type B medicated feed
label. Sections and subsections are not
numbered on the proprietary Type B
medicated feed label.
(1) Proprietary Type B medicated feed
identification. This section of the
proprietary Type B medicated feed label
must include in order:
(i) Proprietary name of the Type B
medicated feed; and
(ii) Established name of the Type B
medicated feed. The established name
of the Type B medicated feed must
include in the following order:
(A) The active moiety or active
ingredient of each new animal drug, as
determined by FDA; and
(B) One of the following statements,
as applicable: ‘‘Type B medicated feed’’
or ‘‘Type B liquid medicated feed’’.
(2) VFD cautionary statement. The
requirements of paragraph (a)(2) of this
section apply.
(3) Undiluted statement. This section
of the proprietary Type B medicated
feed label must include the statement:
‘‘Do Not Feed Undiluted’’.
(4) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(5) ‘‘Indications for Use’’. The
requirements of § 201.407(a)(3) apply.
(6) Extralabel use statement. The
requirements of paragraph (a)(6) of this
section apply.
(7) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the
proprietary Type B medicated feed label
must include the established name and
concentration of each active ingredient
in the proprietary Type B medicated
feed. If the proprietary Type B
medicated feed contains one active
ingredient, this section of the
proprietary Type B medicated feed label
must be entitled ‘‘Active Ingredient.’’ If
the proprietary Type B medicated feed
contains more than one active
ingredient, this section of the
proprietary Type B medicated feed label
must be entitled ‘‘Active Ingredients.’’
(8) ‘‘Guaranteed Analysis’’. This
section of the proprietary Type B
medicated feed label must provide the
nutritional content guarantees of the
proprietary Type B medicated feed
appropriate for the target animal(s) in
addition to any other required
specifications.
(9) ‘‘Ingredients’’. This section of the
proprietary Type B medicated feed label
must include:
(i) A listing of the feed ingredients in
the proprietary Type B medicated feed
by their common or usual names in
descending order of predominance by
weight, in accordance with § 501.4(a) of
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this chapter, including their collective
names where permitted, in accordance
with § 501.4(b)(13) of this chapter; and
(ii) A declaration of spices, flavorings,
colorings, and chemical preservatives, if
used, in accordance with § 501.22 of
this chapter.
(10) ‘‘Mixing Directions’’. This section
of the proprietary Type B medicated
feed label must provide the approved
mixing directions for the manufacture of
a Type C medicated feed(s) or another
Type B medicated feed(s), as applicable,
from the proprietary Type B medicated
feed.
(11) ‘‘Warnings’’. The requirements of
paragraph (a)(10) of this section apply.
(12) ‘‘Additional Recommendations’’.
The requirements of § 201.407(a)(8)
apply.
(13) ‘‘Other Effects You May Notice’’.
The requirements of § 201.407(a)(9)
apply.
(14) ‘‘Net Weight’’. This section of the
proprietary Type B medicated feed label
must list the net weight of the Type B
medicated feed in the immediate
container.
(15) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(16) ‘‘Questions/Comments?’’. The
following statements must be included
in this section of the proprietary Type
B medicated feed label: ‘‘Contact [insert
name of business] at [insert business
telephone number] or [insert business
web address]. For additional
information about reporting problems
with medicated feeds, contact FDA at
[insert current FDA telephone number
for voluntary reporting of adverse drug
experiences] or [insert current FDA web
address for voluntary reporting of
adverse drug experiences].’’ Use as the
name of the business the manufacturer,
packer, or distributor identified in the
‘‘Name and place of business’’ section of
the proprietary Type B medicated feed
label according to paragraph (d)(18) of
this section. If more than one business
is identified in the ‘‘Name and place of
business’’ section of the proprietary
Type B medicated feed label, select the
most appropriate to identify as the
‘‘business’’ in the ‘‘Questions/
Comments?’’ section of the proprietary
Type B medicated feed label to provide
additional information about the Type B
medicated feed and to contact regarding
problems with this medicated feed.
(17) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of
§ 201.405(a)(21) apply.
(18) Name and place of business. The
requirements of § 201.405(a)(22) apply.
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(19) ‘‘Lot, Batch, or Control Number’’.
This section of the proprietary Type B
medicated feed label must include the
identifying lot, batch, or control number
of the Type B medicated feed.
Alternatively, this section must refer to
the location on the proprietary Type B
medicated feed label or immediate
container where the lot, batch, or
control number is printed.
(20) ‘‘Expiration Date’’. If an
expiration date is required, in
accordance with § 514.1(b)(5)(x) of this
chapter, this section must be included
on the proprietary Type B medicated
feed label and must provide the
expiration date of the proprietary Type
B medicated feed. Alternatively, this
section must refer to the location on the
proprietary Type B medicated feed label
or immediate container where the
expiration date is printed.
(21) ‘‘Revision Date’’. This section of
the proprietary Type B medicated feed
label must include the date of the most
recent revision of the proprietary Type
B medicated feed label, listing the
month followed by the year.
(e) Proprietary Type C medicated feed
label. The following information, as
applicable, must appear in the order
listed on the proprietary Type C
medicated feed label. Section headings,
subsection headings, and other text
presented in quotations in this
paragraph must appear verbatim on the
proprietary Type C medicated feed
label. Sections and subsections are not
numbered on the proprietary Type C
medicated feed label.
(1) Proprietary Type C medicated feed
identification. This section of the
proprietary Type C medicated feed label
must include in order:
(i) Proprietary name of the Type C
medicated feed; and
(ii) Established name of the Type C
medicated feed. The established name
of the Type C medicated feed must
include in the following order:
(A) The active moiety or active
ingredient of each new animal drug, as
determined by FDA; and
(B) One of the following statements,
as applicable: ‘‘Type C medicated feed,’’
‘‘Type C liquid medicated feed,’’ ‘‘Type
C top-dress medicated feed,’’ ‘‘Type C
free-choice medicated feed,’’ or ‘‘Type C
liquid free-choice medicated feed.’’
(2) VFD cautionary statement. The
requirements of paragraph (a)(2) of this
section apply.
(3) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(4) ‘‘Indications for Use’’. The
requirements of § 201.407(a)(3) apply.
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(5) Extralabel use statement. The
requirements of paragraph (a)(6) of this
section apply.
(6) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the
proprietary Type C medicated feed label
must include the established name and
concentration of each active ingredient
in the proprietary Type C medicated
feed. If the proprietary Type C
medicated feed contains one active
ingredient, this section of the
proprietary Type C medicated feed label
must be entitled ‘‘Active Ingredient.’’ If
the proprietary Type C medicated feed
contains more than one active
ingredient, this section of the
proprietary Type C medicated feed label
must be entitled ‘‘Active Ingredients.’’
(7) ‘‘Guaranteed Analysis’’. The
requirements of paragraph (d)(8) of this
section apply.
(8) ‘‘Ingredients’’. The requirements of
paragraph (d)(9) of this section apply.
(9) ‘‘Feeding Directions’’. This section
of the proprietary Type C medicated
feed label must include the approved
feeding directions for the proprietary
Type C medicated feed.
(10) ‘‘Warnings’’. The requirements of
paragraph (a)(10) of this section apply.
(11) ‘‘Additional Recommendations’’.
The requirements of § 201.407(a)(8)
apply.
(12) ‘‘Other Effects You May Notice’’.
The requirements of § 201.407(a)(9)
apply.
(13) ‘‘Net Weight’’. This section of the
proprietary Type C medicated feed label
must list the net weight of the Type C
medicated feed in the immediate
container.
(14) ‘‘Storage, Handling, and
Disposal’’. The requirements of
§ 201.405(a)(20) apply.
(15) ‘‘Questions/Comments?’’. The
following statements must be included
in this section of the proprietary Type
C medicated feed label: ‘‘Contact [insert
name of business] at [insert business
telephone number] or [insert business
web address]. For additional
information about reporting side effects
or other problems with medicated feeds,
contact FDA at [insert current FDA
telephone number for voluntary
reporting of adverse drug experiences]
or [insert current FDA web address for
voluntary reporting of adverse drug
experiences].’’ Use as the name of the
business the manufacturer, packer, or
distributor identified in the ‘‘Name and
place of business’’ section of the
proprietary Type C medicated feed label
according to paragraph (e)(17) of this
section. If more than one business is
identified in the ‘‘Name and place of
business’’ section of the proprietary
Type C medicated feed label, select the
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most appropriate to identify as the
‘‘business’’ in the ‘‘Questions/
Comments?’’ section of the proprietary
Type C medicated feed label to provide
additional information about the Type C
medicated feed and to contact regarding
suspected adverse drug experiences.
(16) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of
§ 201.405(a)(21) apply.
(17) Name and place of business. The
requirements of § 201.405(a)(22) apply.
(18) ‘‘Lot, Batch, or Control Number’’.
This section of the proprietary Type C
medicated feed label must include the
identifying lot, batch, or control number
of the Type C medicated feed.
Alternatively, this section must refer to
the location on the proprietary Type C
medicated feed label or immediate
container where the lot, batch, or
control number is printed.
(19) ‘‘Expiration Date’’. If an
expiration date is required, in
accordance with § 514.1(b)(5)(x) of this
chapter, this section must be included
on the proprietary Type C medicated
feed label and must provide the
expiration date of the proprietary Type
C medicated feed label. Alternatively,
this section must refer to the location on
the proprietary Type C medicated feed
label or immediate container where the
expiration date is printed.
(20) ‘‘Revision Date’’. This section of
the proprietary Type C medicated feed
label must include the date of the most
recent revision of the proprietary Type
C medicated feed label, listing the
month followed by the year.
(f) Other approved labeling for Type A
medicated articles. If other approved
labeling associated with approved or
conditionally approved Type A
medicated articles is provided (other
approved labeling for Type A medicated
articles), such as shipping labeling, the
following information, as applicable,
must appear in the order listed on the
other approved labeling for Type A
medicated articles. Section headings
and other text presented in quotations
in this paragraph must appear verbatim
on the other approved labeling for Type
A medicated articles. Sections are not
numbered on other approved labeling
for Type A medicated articles.
(1) Type A medicated article
identification. This section of the other
approved labeling for Type A medicated
articles must include in order:
(i) Proprietary name of the Type A
medicated article; and
(ii) Established name of the Type A
medicated article.
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(2) VFD cautionary statement. The
requirements of paragraph (a)(2) of this
section apply.
(3) ‘‘Active Ingredient’’ or ‘‘Active
Ingredients’’. This section of the other
approved labeling for Type A medicated
articles must provide the established
name and concentration of each active
ingredient in the Type A medicated
article. If the Type A medicated article
contains one active ingredient, this
section of the other approved labeling
for Type A medicated articles must be
entitled ‘‘Active Ingredient.’’ If the Type
A medicated article contains more than
one active ingredient, this section of the
other approved labeling for Type A
medicated articles must be entitled
‘‘Active Ingredients.’’
(4) Conditional approval statement.
The requirements of § 201.405(a)(3)
apply.
(5) ‘‘Net Contents’’. This section of the
other approved labeling for Type A
medicated articles must identify the
contents of the container to which the
other approved labeling for Type A
medicated articles applies.
(6) ‘‘Storage and Handling’’. This
section of the other approved labeling
for Type A medicated articles must
include storage information for the Type
A medicated article. If required by FDA
to facilitate the drug’s safe and effective
use, also include handling information.
(7) NADA/ANADA approval
statement. For approved new animal
drugs or approved generic new animal
drugs, the requirements of
§ 201.405(a)(21) apply.
(8) Name and place of business. The
requirements of § 201.405(a)(22) apply.
(9) ‘‘Lot Number and Expiration
Date’’. This section of the other
approved labeling for Type A medicated
articles must include the identifying lot
or control number(s) and the expiration
date(s) of the Type A medicated article
within the container.
(10) ‘‘Revision Date’’. This section of
the other approved labeling for Type A
medicated articles must include the date
of the most recent revision of the other
approved labeling for Type A medicated
articles, listing the month followed by
the year.
§ 201.411 Exemptions from labeling
requirements for approved or conditionally
approved new animal drugs.
(a) In response to a request from the
sponsor that includes the information in
paragraph (b) of this section, FDA may
exempt, based on the circumstances
presented, one or more specific
requirements set forth in this subpart. A
separate request must be submitted for
each approved or conditionally
approved new animal drug for which an
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exemption is sought. Sponsors must
submit such requests to the application
or the investigational new animal drug
file (INAD) for the new animal drug.
Requests will be granted or denied by
the Director of FDA’s Center for
Veterinary Medicine or the Director’s
designee.
(b) Exemption requests must:
(1) Describe why the particular
requirement for which the exemption is
requested is not appropriate for the new
animal drug;
(2) Describe why granting the
exemption would not adversely impact
the safety or effectiveness of the use of
the new animal drug; and
(3) Include copies of all draft labeling
proposed to be used for the new animal
drug.
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§ 201.413 Labeling requirements for
certain approved or conditionally approved
new animal drugs.
In addition to labeling requirements
elsewhere in this subpart, the labeling
requirements in this section apply to the
following approved or conditionally
approved new animal drugs:
(a) Approved or conditionally
approved corticosteroid-containing new
animal drugs for oral, injectable, and/or
ophthalmic use. Approved or
conditionally approved corticosteroidcontaining new animal drugs for oral,
injectable, and/or ophthalmic use are
subject to the labeling requirements for
Rx new animal drugs in this subpart. In
view of adverse reproductive effects
associated with use of certain
corticosteroid drugs in animals,
approved or conditionally approved
corticosteroid new animal drugs
intended for oral and/or injectable use
must also include the following
statements in the ‘‘Animal Safety
Warnings and Precautions’’ subsection
of labeling: ‘‘Clinical and experimental
data have demonstrated that
corticosteroids administered orally or by
injection to animals may induce the first
stage of parturition if used during the
last trimester of pregnancy and may
precipitate premature parturition
followed by dystocia, fetal death,
retained placenta, and metritis.
Additionally, corticosteroids
administered during pregnancy can be
teratogenic.’’ These statements must
also be included in the ‘‘Animal Safety
Warnings and Precautions’’ subsection
of labeling for approved or conditionally
approved corticosteroid new animal
drugs intended for ophthalmic use, if
required by FDA to facilitate the drug’s
safe and effective use.
(b) Anthelmintic new animal drugs—
(1) OTC anthelmintic new animal drugs.
To ensure that OTC anthelmintic new
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animal drugs provide adequate
directions for their effective use, all
approved or conditionally approved
OTC anthelmintic new animal drugs,
including OTC anthelmintic new animal
drugs for use in animal feeds, must
include the following statement in the
‘‘Additional Recommendations’’ section
of labeling: ‘‘Consult your veterinarian
for assistance in the diagnosis,
treatment, and control of parasitism.’’
(2) Anthelmintic new animal drugs for
use in sheep, goats, cattle, horses, swine,
and/or poultry. All approved or
conditionally approved anthelmintic
new animal drugs for use in sheep,
goats, cattle, horses, swine, and/or
poultry must include statements on
their labeling providing information to
end users to minimize antiparasitic
resistance development, including
information on appropriate dosing,
anthelmintic drug selection,
effectiveness monitoring, the integration
of anthelmintic drug use with other
parasite management practices, and
other information as needed. The
statements must be included in the
‘‘Other Warnings’’ subsection of
labeling, and if applicable, additional
statements may be required in the
‘‘Dosage and Administration’’ section of
labeling for Rx anthelmintic new animal
drugs, the ‘‘Directions’’ section of
labeling for OTC anthelmintic new
animal drugs, or the ‘‘Feeding
Directions’’ section or subsection of
labeling for anthelmintic new animal
drugs for use in animal feeds.
(c) New animal drugs for use in
horses. All new animal drugs approved
or conditionally approved for use in
horses must include in the ‘‘Other
Warnings’’ subsection of labeling a
statement advising against the use of the
drug in horses intended for human
consumption.
PART 500—GENERAL
6. The authority citation for part 500
continues to read as follows:
■
Authority: 21 U.S.C. 321, 331, 342, 343,
348, 351, 352, 353, 360b, 371, 379e.
§§ 500.25 and 500.55
■
[Removed]
7. Remove §§ 500.25 and 500.55.
PART 501—ANIMAL FOOD LABELING
8. The authority citation for part 501
continues to read as follows:
■
Authority: 15 U.S.C. 1453, 1454, 1455; 21
U.S.C. 321, 331, 342, 343, 348, 371.
9. Add § 501.19 to subpart A to read
as follows:
■
PO 00000
Frm 00076
Fmt 4701
Sfmt 4702
§ 501.19 Animal food; labeling of animal
food containing new animal drugs.
The requirements for the labeling of
animal food containing an approved or
conditionally approved new animal
drug are found in § 201.409 of this
chapter. Requirements of this part apply
only as specified in § 201.409.
PART 510—NEW ANIMAL DRUGS
10. The authority citation for part 510
continues to read as follows:
■
Authority: 21 U.S.C. 321, 331, 351, 352,
353, 360b, 371, 379e.
§§ 510.105, 510.106, and 510.410
[Removed]
11. Remove §§ 510.105, 510.106, and
510.410.
■
PART 514—NEW ANIMAL DRUG
APPLICATIONS
12. The authority citation for part 514
continues to read as follows:
■
Authority: 21 U.S.C. 321, 331, 351, 352,
354, 356a, 360b, 360ccc, 371, 379e, 381.
13. In § 514.1, revise paragraph (b)(3)
to read as follows:
■
§ 514.1
Applications.
*
*
*
*
*
(b) * * *
(3) Labeling. Three copies of each
piece of all labeling to be used for the
article (total of 9).
(i) All labeling should be identified to
show its position on, or the manner in
which it is to accompany the market
package.
(ii) The content and format of all
proposed labeling must comply with
subpart H of part 201 of this chapter.
(iii) Labeling for nonprescription new
animal drugs should include adequate
directions for use by the layperson
under all conditions of use for which
the new animal drug is intended,
recommended, or suggested in any of
the labeling or advertising sponsored by
the applicant.
(iv) Labeling for prescription new
animal drugs should bear adequate
information for use under which
veterinarians can use the new animal
drug safely and for the purposes for
which it is intended, including those
purposes for which it is to be advertised
or represented, in accord with § 201.105
of this chapter.
(v) All labeling for prescription or
nonprescription new animal drugs must
be submitted with any necessary use
restrictions prominently and
conspicuously displayed.
(vi) Labeling for new animal drugs
intended for use in the manufacture of
medicated feeds must include:
E:\FR\FM\12MRP3.SGM
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Federal Register / Vol. 89, No. 49 / Tuesday, March 12, 2024 / Proposed Rules
khammond on DSKJM1Z7X2PROD with PROPOSALS3
(A) Specimens of labeling to be used
for such new animal drug with adequate
directions for the manufacture and use
of finished feeds for all conditions for
which the new animal drug is intended,
recommended, or suggested in any of
the labeling, including advertising,
sponsored by the applicant. Ingredient
labeling may utilize collective names as
provided in § 501.110 of this chapter.
(B) Representative labeling proposed
to be used for Type B and Type C
medicated feeds containing the new
animal drug.
(vii) Draft labeling may be submitted
for preliminary consideration of an
application. Final printed labeling will
ordinarily be required prior to approval
of an application. Proposed advertising
VerDate Sep<11>2014
21:04 Mar 11, 2024
Jkt 262001
for prescription new animal drugs may
be submitted for comment or approval.
*
*
*
*
*
PART 516—NEW ANIMAL DRUGS FOR
MINOR USE AND MINOR SPECIES
14. The authority citation for part 516
continues to read as follows:
■
Authority: 21 U.S.C. 360ccc–1, 360ccc–2,
371.
15. In § 516.155, redesignate
paragraph (c) as paragraph (d) and add
a new paragraph (c) to read as follows:
■
§ 516.155
Labeling of indexed drugs.
*
*
*
*
*
(c) To ensure that OTC anthelmintic
new animal drugs provide adequate
directions for their effective use, the
PO 00000
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18337
labeling of all OTC indexed
anthelmintic drugs, including those
used in animal feeds, must include the
following statement: ‘‘Consult your
veterinarian for assistance in the
diagnosis, treatment, and control of
parasitism.’’ The labeling revisions
required for compliance with this
section may be placed into effect
without prior granting of a request for a
modification, as provided for in
§ 516.161(b)(1).
*
*
*
*
*
Dated: March 1, 2024.
Robert M. Califf,
Commissioner of Food and Drugs.
[FR Doc. 2024–04840 Filed 3–8–24; 8:45 am]
BILLING CODE 4164–01–P
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]]>Agencies
[Federal Register Volume 89, Number 49 (Tuesday, March 12, 2024)]
[Proposed Rules]
[Pages 18262-18337]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-04840]
[[Page 18261]]
Vol. 89
Tuesday,
No. 49
March 12, 2024
Part V
Department of Health and Human Services
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Food and Drug Administration
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21 CFR Parts 201, 500, 501, et al.
Labeling Requirements for Approved or Conditionally Approved New Animal
Drugs; Proposed Rule
Federal Register / Vol. 89 , No. 49 / Tuesday, March 12, 2024 /
Proposed Rules
[[Page 18262]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 201, 500, 501, 510, 514, and 516
[Docket No. FDA-2023-N-5160]
RIN 0910-AI43
Labeling Requirements for Approved or Conditionally Approved New
Animal Drugs
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is proposing to revise
the requirements for the content and format of labeling for approved or
conditionally approved new animal drugs to provide for a more
comprehensive set of requirements in one location in the Code of the
Federal Register (CFR). As part of this revision, certain current
requirements would be updated and moved, and certain obsolete
requirements would be removed. The proposed requirements would apply to
the labeling of prescription and over-the-counter (OTC) new animal
drugs, as well as new animal drugs for use in animal feeds.
DATES: Either electronic or written comments on the proposed rule must
be submitted by June 10, 2024. Submit written comments (including
recommendations) on information collection issues under the Paperwork
Reduction Act of 1995 by April 11, 2024.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of June 10, 2024. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2023-N-5160 for ``Labeling Requirements for Approved or
Conditionally Approved New Animal Drugs.'' Received comments, those
filed in a timely manner (see ADDRESSES), will be placed in the docket
and, except for those submitted as ``Confidential Submissions,''
publicly viewable at https://www.regulations.gov or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents, the
plain language summary of the proposed rule of not more than 100 words
are required by the ``Providing Accountability Through Transparency
Act,'' or the electronic and written/paper comments received, go to
https://www.regulations.gov and insert the docket number, found in
brackets in the heading of this document, into the ``Search'' box and
follow the prompts and/or go to the Dockets Management Staff, 5630
Fishers Lane, Rm. 1061, Rockville, MD 20852.
Submit comments on information collection issues under the
Paperwork Reduction Act of 1995 to the Office of Management and Budget
(OMB) https://www.reginfo.gov/public/do/PRAMain. Find this particular
information collection by selecting ``Currently under Review--Open for
Public Comments'' or by using the search function. The title of this
proposed collection is ``Labeling Requirements for Approved or
Conditionally Approved New Animal Drugs.''
FOR FURTHER INFORMATION CONTACT:
With regard to the proposed rule: Suzanne Sechen, Center for
Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl.,
Rockville, MD 20855, 240-402-0814, [email protected].
With regard to the information collection: Amber Sanford, Office of
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-8867,
[email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose and Coverage of the Proposed Rule
B. Summary of the Major Provisions of the Proposed Rule
C. Legal Authority
D. Costs and Benefits
[[Page 18263]]
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
A. Introduction
B. Need for the Regulation
C. FDA's Current Regulatory Framework
D. History of the Rulemaking
IV. Legal Authority
V. Description of the Proposed Rule
A. Scope (Proposed Sec. 201.401)
B. Definitions (Proposed Sec. 201.403)
C. General Requirements (Proposed Sec. 201.404)
D. Content and Format for Prescription (Rx) New Animal Drug
Labeling--Overview (Proposed Sec. 201.405)
E. Content and Format for Over-The-Counter (OTC) New Animal Drug
Labeling--Overview (Proposed Sec. 201.407)
F. Content and Format of Labeling for New Animal Drugs for Use
in Animal Feeds--Overview (Proposed Sec. 201.409)
G. Exemptions From Labeling Requirements for Approved or
Conditionally Approved New Animal Drugs (Proposed Sec. 201.411)
H. Labeling Requirements for Certain Approved or Conditionally
Approved New Animal Drugs (Proposed Sec. 201.413)
I. Proposed Conforming Amendments
VI. Proposed Effective/Compliance Dates
VII. Preliminary Economic Analysis of Impacts
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Consultation and Coordination With Indian Tribal Governments
XII. References
I. Executive Summary
A. Purpose and Coverage of the Proposed Rule
FDA proposes to revise the existing regulations regarding the
content and format of labeling for approved or conditionally approved
new animal drugs. These proposed regulations would apply to the
labeling of prescription and OTC new animal drugs, as well as new
animal drugs for use in animal feeds. Certain existing regulations
regarding the labeling of new animal drugs would be updated and moved
from their current location and incorporated into the proposed
regulations, including a new subpart H in part 201 (21 CFR part 201).
FDA also proposes to amend or remove certain current regulations to
ensure consistency with the proposed regulations.
Proposed subpart H would not apply to heritable intentional genomic
alterations in animals. Proposed subpart H would also not apply to
labeling of indexed legally marketed unapproved new animal drugs for
minor species. In addition, proposed subpart H would not apply to
promotional labeling or advertising.
B. Summary of the Major Provisions of the Proposed Rule
The proposed rule would revise the existing requirements for the
content and format of labeling for approved or conditionally approved
new animal drugs. If finalized, sponsors of these new animal drugs
would need to comply with these proposed regulations on a staggered
schedule, over the course of 6 years, according to a schedule based on
application number, with approved NADAs with higher application numbers
having the earliest compliance date because they are more recently
approved and therefore likely to need the fewest labeling revisions.
If finalized, this rule would enable FDA to provide sponsors with
predictable requirements for the content and format of labeling for new
animal drugs and codify FDA's longstanding practices with respect to
the review of labeling submitted as part of a new animal drug
application (NADA), certain abbreviated new animal drug applications
(ANADAs) that reference a new animal drug for which the NADA has been
withdrawn, or a new animal drug application for conditional approval
(CNADA).
Currently a comprehensive set of regulations establishing labeling
requirements for the content and format of labeling for new animal
drugs does not exist in the CFR. These proposed regulations would
provide sponsors with predictable requirements for the content and
format of labeling for new animal drugs. Also, these proposed
regulations would help sponsors more efficiently prepare labeling for
new animal drugs to be submitted as part of an NADA, CNADA, or certain
ANADAs by providing clear and consistent requirements for the
information that would need to be included on each component of
labeling for a new animal drug, as well as the format in which the
information is to be presented.
FDA is proposing specific requirements for content and format of
the labeling for approved or conditionally approved prescription and
OTC new animal drugs, as well as approved or conditionally approved new
animal drugs for use in animal feeds.
The proposed regulations would provide the following:
The content and format of labeling components applicable
to approved or conditionally approved new animal drugs.
Definitions of labeling terms for approved or
conditionally approved new animal drugs.
A schedule for sponsors of approved or conditionally
approved and marketed new animal drugs to comply with these proposed
regulations within a maximum of 6 years from the effective date of any
final rule.
Provisions for foreign language translation of the
labeling for approved or conditionally approved new animal drugs.
A process for sponsors of new animal drugs to request
exemptions from the proposed labeling requirements.
Consolidation of the labeling requirements for the content
and format of labeling for approved or conditionally approved new
animal drugs into one section of the regulations. At present, existing
requirements are dispersed throughout the regulations.
C. Legal Authority
FDA's revisions to the content and format requirements for animal
drug labeling are authorized by various provisions of the Federal Food,
Drug, and Cosmetic Act (FD&C Act). The premarket approval provisions of
the FD&C Act authorize FDA to require that new animal drug labeling
provide adequate information to permit safe and effective use of the
drug.
The FD&C Act requires certain information be included on a drug's
label and provides for certain exemptions from these requirements.
Also, the FD&C Act authorizes FDA to establish additional exemptions by
regulation.
The FD&C Act requires that new animal drug applications include
specimens of the labeling proposed to be used for the drug. A new
animal drug will be deemed unsafe if its labeling fails to conform to
the approved labeling in the applicable approved new animal drug
application, conditionally approved new animal drug application, or new
animal drug index listing. Unsafe drugs are deemed adulterated under
the provisions of the FD&C Act. The FD&C Act prohibits the marketing of
drugs that are adulterated or misbranded as well as their adulteration
or misbranding while in interstate commerce.
In addition to the other statutory provisions described above, the
FD&C Act gives the FDA general rulemaking authority to issue
regulations for the efficient enforcement of the FD&C Act.
D. Costs and Benefits
If this proposed rule is finalized, industry and FDA would incur
cost savings from a reduction in the quantity and time burden of new
animal drug labeling amendments and informal communications related to
new animal drug labeling. There may be additional
[[Page 18264]]
benefits to users of approved or conditionally approved new animal
drugs from greater predictability and ease of reading new animal drug
labeling in the form of time saved searching for content, as well as
benefits to animal or human health, which we are unable to quantify.
We expect that new animal drug sponsors would incur one-time costs
to read and understand the rule, revise standard operating procedures
(SOPs) related to labeling, and train employees on the revised SOPs.
New animal drug sponsors would also bear costs to update labeling and
prepare supplemental labeling applications to conform to the proposed
requirements. FDA would incur costs to review these supplemental
applications.
FDA estimates that the annualized benefits over 10 years would
range from $0.143 million to $0.243 million at a 2 percent discount
rate, with a primary estimate of $0.193 million. The annualized costs
would range from $2.16 million to $2.77 million at a 2 percent discount
rate, with a primary estimate of $2.45 million.
II. Table of Abbreviations/Commonly Used Acronyms in This Document
------------------------------------------------------------------------
Abbreviation/acronym What it means
------------------------------------------------------------------------
ADAA......................... Animal Drug Availability Act.
ANADA........................ Abbreviated New Animal Drug Application
CFR.......................... Code of Federal Regulations.
CNADA........................ Conditionally Approved New Animal Drug
Application.
FD&C Act..................... Federal Food, Drug, and Cosmetic Act.
FDA.......................... Food and Drug Administration.
FR........................... Federal Register.
HHS.......................... Health and Human Services.
INAD......................... Investigational New Animal Drug.
MUMS......................... Minor Use Minor Species.
NADA......................... New Animal Drug Application.
NDC.......................... National Drug Code.
NEPA......................... National Environmental Policy Act.
OMB.......................... Office of Management and Budget.
OTC.......................... Over-the-counter.
PCBs......................... Polychlorinated biphenyls.
PRA.......................... Paperwork Reduction Act of 1995.
RLNAD........................ Reference-Listed New Animal Drug.
Rx........................... Prescription.
U.S.......................... United States.
U.S.C........................ United States Code.
VFD.......................... Veterinary Feed Directive.
VMF.......................... Veterinary Master File.
------------------------------------------------------------------------
III. Background
A. Introduction
In accordance with the definition in section 201(k) of the FD&C Act
(21 U.S.C. 321(k)) the ``label'' is a display of written, printed, or
graphic matter upon the immediate container of any article. Under
section 201(m) of the FD&C Act, the term ``labeling'' means ``all
labels and other written, printed, or graphic matter (1) upon any
article or any of its containers or wrappers, or (2) accompanying such
article.'' Labeling, therefore, includes the label of any article,
including new animal drugs.
Under existing regulations, proposed labeling must be included as
part of an application filed with FDA for approval of a new animal
drug, in accordance with section 512(b)(1)(F) of the FD&C Act (21
U.S.C. 360b(b)(1)(F)). Labeling for nonprescription, known as over-the-
counter (OTC), new animal drugs should include adequate directions for
use by the layperson under all conditions of use for which the new
animal drug is intended, recommended, or suggested in any of the
labeling or advertising sponsored by the applicant (see Sec.
514.1(b)(3)(ii) (21 CFR 514.1(b)(3)(ii)). Labeling for prescription new
animal drugs should bear adequate information for use under which
veterinarians can use the new animal drug safely and for the purposes
for which it is intended, including those purposes for which it is to
be advertised or represented, in accordance with Sec. 201.105 (21 CFR
201.105) (see Sec. 514.1(b)(3)(iii)). All labeling for prescription or
OTC new animal drugs must provide any necessary use restrictions
prominently and conspicuously displayed (see Sec. 514.1(b)(3)(iv)).
Labeling for new animal drugs intended for use in the manufacture
of medicated feeds must include: (1) specimens of labeling to be used
for such new animal drug with adequate directions for the manufacture
and use of finished feeds for all conditions for which the new animal
drug is intended, recommended, or suggested in any of the labeling,
including advertising, sponsored by the applicant; and (2)
representative labeling proposed to be used for Type B and Type C
medicated feeds containing the new animal drug (see Sec.
514.1(b)(3)(v)). Sponsors of new animal drug applications commit to
providing labeling for the new animal drug that prescribes, recommends,
or suggests its use only under the conditions stated in the labeling
included as part of the application (see Sec. 514.1(b)(11)). All
representations of labeling in the application apply to the new animal
drug produced until changes are made in conformity with Sec. 514.8 (21
CFR 514.8) (see Sec. 514.1(b)(11)).
Sponsors of new animal drug applications may submit draft labeling
for FDA's preliminary consideration of an application (see Sec.
514.1(b)(3)(vi)). For example, sponsors sometimes include draft
labeling content pertinent to key components of an application that are
submitted for preliminary FDA review (e.g., manufacturing components
and composition, evidence to establish safety and effectiveness, and
environmental assessment).
Under section 502(a)(1) of the FD&C Act (21 U.S.C. 352(a)(1)), a
drug shall be deemed to be misbranded if its labeling is false or
misleading in any particular. A new animal drug for which an approval
or conditional approval is in effect will be considered unsafe if its
labeling fails to conform to the approved or conditionally approved
application (section 512(a)(1)(A) and (B) of the FD&C Act).
[[Page 18265]]
B. Need for the Regulation
Based on FDA's experience in reviewing labeling for approved or
conditionally approved prescription new animal drugs and informal
feedback from sponsors of such new animal drugs in the past 60 years,
it has become clear that sponsors would benefit from having more
detailed requirements on the content, format, and order of information
on labeling so that they can efficiently prepare adequate labeling for
approved or conditionally approved prescription new animal drugs to be
submitted as part of an NADA, CNADA, or certain ANADAs that reference a
new animal drug for which the NADA has been withdrawn.
For example, existing Sec. 201.105(c) provides requirements for
labeling ``on or within the package'' from which prescription animal
drugs are dispensed, and paragraph (d) of that section provides
requirements for all labeling for prescription new animal drugs.
Labeling for prescription new animal drugs typically consists of
multiple components, such as the label, one or more package inserts,
secondary container labeling, multiple unit carton labeling, shipping
labeling, and/or display carton labeling. However, neither paragraph
(c) nor (d) of Sec. 201.105 provides direction on the format or order
of information with respect to specific labeling components.
Furthermore, it is not clear whether the information required by
paragraph (d) of Sec. 201.105 needs to be presented on all components
of labeling for prescription new animal drugs, or if not, what critical
information needs to be provided on specific labeling components,
particularly smaller components of limited size.
Whereas existing Sec. 201.105 provides at least some requirements
for the content of labeling for prescription new animal drugs, there
are currently no regulations that provide requirements for the general
content and format of labeling for OTC new animal drugs and new animal
drugs administered in animal feeds.
The lack of direction regarding format and content for each
component of labeling has resulted in confusion for sponsors as they
prepare labeling for FDA's review and sometimes results in poor quality
labeling submissions. Poor quality labeling submissions increase the
time needed by sponsors to revise and resubmit adequate labeling, and
they increase time needed by FDA to review and approve labeling, and
consequently, the application.
New animal drug labeling that presents information in an
inconsistent manner can contribute to medication errors by making it
difficult for veterinarians and animal owners to readily locate and
understand critical directions and safety information. Information in
the labeling for approved or conditionally approved new animal drugs
presented in a consistent manner communicates information that is
important to the safe use of a new animal drug in the medication use
process (i.e., from prescription, to procurement, preparation, and
dispensing and administration of the medication to the animal).
Other regulations specifically pertaining to the labeling of
certain new animal drugs include Sec. 500.25 (21 CFR 500.25),
``Anthelmintic drugs for use in animals,'' Sec. 500.55 (21 CFR
500.55), ``Exemption from certain drug-labeling requirements,'' Sec.
510.105 (21 CFR 510.105), ``Labeling of drugs for use in milk-producing
animals,'' Sec. 510.106 (21 CFR 510.106), ``Labeling of antibiotic and
antibiotic-containing drugs intended for use in milk-producing
animals,'' and Sec. 510.410 (21 CFR 510.410), ``Corticosteroids for
oral, injectable, and ophthalmic use in animals; warnings and labeling
requirements.''
The proposed rule would locate the labeling requirements for
``Anthelmintic drugs for use in animals,'' currently in Sec. 500.25,
with other labeling requirements for new animal drugs.
The proposed rule would remove the exemption in Sec. 500.55,
``Exemption from certain drug-labeling requirements,'' because we
believe that full disclosure labeling is needed for all prescription
new animal drugs to ensure veterinarians are able to use these products
safely and effectively.
In addition, the proposed rule would remove the labeling
requirements in Sec. 510.105, ``Labeling of drugs for use in milk-
producing animals,'' and Sec. 510.106, ``Labeling of antibiotic and
antibiotic-containing drugs intended for use in milk-producing
animals.'' The labeling requirements in these regulations do not
provide adequate flexibility for targeted and informative statements
with respect to human food safety warnings, including milk discard
times, withdrawal periods, and residue warning statements for the
labeling of new animal drugs intended for use in milk-producing
animals.
Section 510.410, ``Corticosteroids for oral, injectable, and
ophthalmic use in animals; warnings and labeling requirements,''
contains background information and warning and labeling requirements
for this category of new animal drugs. We propose a conforming
amendment to remove Sec. 510.410 and to move portions of that section
to be located with the other labeling requirements for new animal
drugs.
C. FDA's Current Regulatory Framework
Current Sec. 201.105 provides conditions that must be met for
exempting prescription animal drugs from section 502(f)(1) of the FD&C
Act, which requires the labeling to bear adequate directions for use.
Section 201.105(b) requires the following information to appear on the
label for prescription animal drugs for such products to be exempt from
section 502(f)(1) of the FD&C Act:
a standard statement restricting use to or on the order of
a licensed veterinarian,
dosage,
route of administration if it is not oral,
quantity or proportion of each active ingredient as well
as information required, in accordance with section 502(e) of the FD&C
Act,
names of inactive ingredients if the drug is for other
than oral use (with some exemptions), and
an identifying lot or control number.
For containers too small or otherwise unable to fit a label with
enough space to display all the required information, Sec. 201.105(b)
allows eliminating some information from these labels and placing it on
other approved labeling.
Labeling for prescription new animal drugs must bear adequate
information for use, including indications, effects, dosages, routes,
methods, and frequency and duration of administration; any relevant
warnings, hazards, contraindications, side effects, and precautions
under which veterinarians can use the drug safely and for the intended
purposes; and ingredient information as required for the label (see
Sec. 201.105(c) through (e)). All prescription animal drug labeling,
except for labels and cartons, must bear the issuance dates of the
latest revisions of such labeling (see Sec. 201.105(e)). Applicants
may submit a written request to the Commissioner of Food and Drugs for
an exemption from inclusion of adequate information for use required in
Sec. 201.105(c)(1) from the dispensing package of prescription new
animal drugs for which directions, hazards, warnings, and use
information are commonly known to licensed veterinarians (see Sec.
201.105(c)(2)).
A prescription drug intended for both human and veterinary use must
comply with paragraphs (e) and (f) of Sec. 201.105, in addition to
Sec. 201.100, which provides
[[Page 18266]]
requirements for prescription drugs for human use (see Sec.
201.105(f)).
D. History of the Rulemaking
In 1955, FDA issued regulations at Sec. 1.106(c) establishing
requirements primarily for the label of prescription animal drugs (20
FR 9525 at 9533, December 20, 1955). The initial requirements were
expanded in 1960 to cover the labeling of such drugs more fully (25 FR
12592, December 9, 1960). As part of FDA's reorganization of its
regulations, in 1975 Sec. 1.106(c) was redesignated as Sec. 201.105
(40 FR 13494 at 13496, March 27, 1975). Most provisions in current
Sec. 201.105 are similar to the 1960 version of Sec. 1.106(c).
IV. Legal Authority
FDA's revisions to the content and format requirements for animal
drug labeling are authorized by various provisions of the FD&C Act,
including sections 201, 301, 501, 502, 503, 504, 512, 571, and 701 (21
U.S.C. 321, 331, 351, 352, 353, 354, 360b, 360ccc, and 371). Section
201 contains definitions relevant to the proposed content and format
requirements, including for the terms ``label'' and ``labeling''.
Pursuant to section 201(k) of the FD&C Act, the term ``label'' means
``a display of written, printed, or graphic matter upon the immediate
container of any article.'' That provision requires that any words,
statements, or other information appearing on the label also appear on
the outside container or wrapper of the retail package, or be easily
legible through the outside container or wrapper. Section 201(m) of the
FD&C Act defines ``labeling'' to mean ``all labels and other written,
printed, or graphic matter (1) upon any article or any of its
containers or wrappers, or (2) accompanying such article.''
Section 301 of the FD&C Act prohibits the marketing of drugs that
are adulterated or misbranded as well as their adulteration or
misbranding while in interstate commerce. Section 501(a)(5) of the FD&C
Act deems a new animal drug to be adulterated if it is unsafe within
the meaning of section 512 of the FD&C Act. Under section 512 of the
FD&C Act, a new animal drug will be deemed unsafe if its labeling fails
to conform to the applicable approved application under section 512 of
the FD&C Act, conditionally approved application under section 571 of
the FD&C Act, or index listing under section 572 of the FD&C Act (21
U.S.C. 360ccc-1).
Section 502 of the FD&C Act specifies conditions that cause a drug
to be misbranded. Under section 502(a) of the FD&C Act, a drug is
deemed to be misbranded if its labeling is false or misleading ``in any
particular.'' Section 201(n) of the FD&C Act deems a product's labeling
misleading if it fails to reveal facts regarding the consequences that
may result from using the article under the conditions of use
prescribed in the labeling or under such conditions of use as are
customary or usual. Under section 502(b) of the FD&C Act, a drug in
package form is deemed to be misbranded unless its label bears the name
and place of business of the manufacturer, packer, or distributor, and
it contains an accurate statement of the quantity of the contents in
terms of weight, measure, or numerical count. Section 502(c) of the
FD&C Act, deems a drug misbranded if any word, statement, or other
information required by law or regulation to be included on the label
or labeling does not appear with such prominence and conspicuousness,
and in such terms, that it is likely to be read and understood by
ordinary individuals under customary conditions of purchase and use.
Section 502(e) of the FD&C Act specifies requirements for including
the established name of the drug and for listing the active and
inactive ingredients on the drug's label. It also provides for certain
exemptions from the requirement to list active and inactive ingredients
and authorizes the Secretary to establish additional exemptions from
some of the requirements in section 502(e) by promulgating regulations
where compliance would be impracticable.
Section 502(f) of the FD&C Act deems a drug to be misbranded if its
labeling lacks adequate directions for use and adequate warnings
against use in those pathological conditions where its use may be
dangerous to health, as well as adequate warnings against unsafe dosage
or methods or duration of administration or application, in such manner
and form, as are necessary for the protection of users.
Section 502(j) of the FD&C Act deems a drug to be misbranded if it
is dangerous to health when used in the dosage or manner, or with the
frequency or duration, prescribed, recommended, or suggested in its
labeling.
Under section 502(w)(1) of the FD&C Act, a new animal drug that has
been conditionally approved is deemed to be misbranded if its labeling
fails to conform with the approved application or fails to include the
labeling information required under section 571(f) of the FD&C Act.
Section 571(f) requires the label and labeling of a new animal drug
with a conditional approval to contain the statement ``conditionally
approved by FDA pending a full demonstration of effectiveness under
application number,'' in addition to other information as required by
the Secretary. Effective September 30, 2023, section 502(w)(3) requires
the labeling of new animal drugs that have received approval under
section 512 of the FD&C Act to include the application number in the
format ``Approved by FDA under (A)NADA # xxx-xxx.''
Section 503(f) of the FD&C Act provides certain labeling
requirements specific to prescription animal drugs, including a
required cautionary statement. Section 503(f)(2) exempts prescription
animal drugs from having to comply with some of the requirements in
section 502 of the FD&C Act, including the requirement for there to be
adequate directions for use (section 502(f)), provided certain
dispensing and labeling requirements specified in section 503(f) are
met.
Section 504 of the FD&C Act authorizes the Secretary to issue
regulations specific to veterinary feed directive (VFD) drugs for use
in or on animal feed, including regulations prescribing a cautionary
statement and other information to be included on the labeling of VFD
drugs and animal feed containing such drugs. Under section 504(b), VFD
drugs and feed containing such drugs will be deemed to be misbranded if
their labeling fails to include such required information.
In addition, the premarket approval provisions of the FD&C Act
authorize FDA to require that animal drug labeling provide adequate
information to permit safe and effective use of the drug. Under section
512 of the FD&C Act, FDA will approve a NADA only if the drug is shown
to be both safe and effective under the conditions of use set forth in
the drug's labeling. Under section 571 of the FD&C Act, FDA will
conditionally approve a new animal drug application (CNADA) only if the
drug is shown to be safe, and there is a reasonable expectation of
effectiveness for use, under the conditions of use set forth in the
drug's labeling. Section 512(b)(1)(F) of the FD&C Act requires that the
application for approval of a new animal drug include specimens of the
labeling proposed to be used for the drug. A new animal drug that has
been approved or conditionally approved by FDA will be deemed to be
unsafe (and therefore adulterated under section 501(a)(5) of the FD&C
Act) if its labeling does not conform to its approved application.
In addition to the other statutory provisions described above,
section 701(a) of the FD&C Act gives the Secretary general rulemaking
authority
[[Page 18267]]
to issue regulations for the efficient enforcement of the FD&C Act.
FDA has previously issued implementing regulations governing the
format and content of labeling for animal drugs. This proposed rule,
when finalized, would revise the content and format of labeling
requirements applicable to approved and conditionally approved new
animal drugs and would consolidate these requirements in subpart H of
part 201.
V. Description of the Proposed Rule
FDA proposes to add subpart H to part 201 (hereafter called
proposed subpart H) to revise the existing requirements for the content
and format of labeling for approved or conditionally approved new
animal drugs. Proposed subpart H would be titled ``Labeling
Requirements for Approved or Conditionally Approved New Animal Drugs''
and would apply to new animal drugs that are approved under section 512
of the FD&C Act or conditionally approved under section 571 of the FD&C
Act. These regulations would not apply to legally marketed unapproved
new animal drugs for minor species that are indexed in accordance with
section 572 of the FD&C Act. These regulations would not apply to the
labeling of heritable intentional genomic alterations in animals, or to
promotional labeling or advertising.
Sponsors of approved or conditionally approved and marketed new
animal drugs would need to comply with these requirements per the
schedule in proposed Sec. 201.404(a)(4), (b), (c), or (d). Consistent
with current practice, we expect that sponsors of new animal drugs that
are the subject of an ANADA approved or submitted pursuant to section
512(n) of the FD&C Act (i.e., a generic new animal drug) will submit a
supplemental application to their ANADA to conform the labeling of
their generic new animal drugs with the revised labeling of the
reference-listed new animal drug (RLNAD). Therefore, in the preliminary
regulatory impact analysis we examine the costs and benefits of these
requirements for ANADAs that reference an NADA that has not been
withdrawn. However, for generic new animal drugs that are the subject
of an ANADA that reference a new animal drug for which the NADA has
been voluntarily withdrawn for reasons other than safety or
effectiveness, or that reference a new animal drug for which the NADA
that has been withdrawn on the basis of one or more of the grounds
included under section 512(e) of FD&C Act and for which the ANADA's
approval was not affected by the withdrawal, labeling for such ANADAs
would need to comply with proposed subpart H per the proposed schedule
described in proposed Sec. 201.404(a)(4)(iii).
The proposed requirements are based on FDA's experience in
reviewing labeling submitted for the approval or conditional approval
of new animal drugs and its experience in implementing existing
regulations for labeling of new animal drugs, as well as input received
from new animal drug sponsors, end users of animal drugs, information
collected from post approval surveillance, and other stakeholders. We
intend for these proposed regulations to provide consistent formatting
of new animal drug labeling by identifying the specific labeling
components that would be required and permitted for each new animal
drug, the information needed for each component, and the order in which
information would appear on labeling. Consistent and standardized
content and format of new animal drug labeling may make it easier for
end users (veterinarians, animal owners, or persons treating the
animals) to access, read, and use the information to make informed
decisions quickly, while promoting safe use of the drug. Such labeling
may contribute to reducing medication errors.
Providing clear and consistent requirements in these proposed
regulations should help to reduce the amount of time needed by sponsors
of new animal drugs to prepare high quality proposed labeling for their
new animal drugs. The submission of higher quality proposed labeling by
sponsors of new animal drugs may reduce the amount of time needed by
FDA to review and approve labeling, and consequently, the new animal
drug application.
We include the following eight sections in proposed subpart H:
Sec. 201.401 Scope.
Sec. 201.403 Definitions.
Sec. 201.404 General requirements.
Sec. 201.405 Content and format for prescription new
animal drug labeling.
Sec. 201.407 Content and format for OTC new animal drug
labeling.
Sec. 201.409 Content and format of labeling for new
animal drugs for use in animal feeds.
Sec. 201.411 Exemptions from labeling requirements for
approved or conditionally approved new animal drugs.
Sec. 201.413 Labeling requirements for certain approved
or conditionally approved new animal drugs.
A. Scope (Proposed Sec. 201.401)
The proposed rule would revise the existing requirements for the
content and format of labeling for prescription (Rx) new animal drugs,
OTC new animal drugs other than those for use in animal feeds in
accordance with part 558 (21 CFR part 558), and new animal drugs for
use in animal feeds that are subject to part 558, including VFD drugs,
that are subject of the specific applications identified in proposed
Sec. 201.401(a)(1) through (4).
Subpart H would apply to the labeling of new animal drugs that are
the subject of an NADA approved or submitted pursuant to section 512 of
the FD&C Act (see proposed Sec. 201.401(a)(1)), new animal drugs that
are the subject of a CNADA conditionally approved or submitted pursuant
to section 571 of the FD&C Act (see proposed Sec. 201.401(a)(2)), and
new animal drugs that are the subject of an ANADA approved or submitted
pursuant to section 512(n) of the FD&C Act (i.e., a generic new animal
drug) that reference a new animal drug for which the NADA has been
voluntarily withdrawn for reasons other than safety or effectiveness,
or that reference a new animal drug for which the NADA has been
withdrawn on the basis of one or more of the grounds included under
section 512(e) of the FD&C Act and for which the generic new animal
drug's approval was not affected by the withdrawal (see proposed Sec.
201.401(a)(3)).
For some proprietary Type B or Type C medicated feeds, the
formulation and labeling are approved and maintained in an NADA or
CNADA file. In other situations, the underlying data and labeling for
the proprietary Type B or Type C medicated feed to support the approved
uses are maintained in a Veterinary Master File (VMF). The latter would
include, as an example, situations in which a proprietary Type B or
Type C medicated feed is manufactured via modification to an approved
formulation published in the CFR or where a feed manufacturer creates
its own proprietary formulation. The labeling of these proprietary
medicated feeds is maintained in a VMF and would be required to comply
with proposed subpart H (see proposed Sec. 201.401(a)(4)).
The proposed requirements would apply to the applications described
in proposed Sec. 201.401(a)(1) through (4) for new animal drugs that
are approved before the effective date of any final rule based on this
proposed rule, pending on the effective date of any final rule based on
this proposed rule, or submitted on
[[Page 18268]]
or after the effective date of any final rule based on this proposed
rule (see proposed Sec. 201.401(c)). The schedule for compliance is
provided in proposed Sec. 201.404(a)(4).
The proposed requirements would deem any approved or conditionally
approved new animal drug subject to this subpart that does not fully
comply with the applicable requirements in accordance with the schedule
proposed in Sec. 201.404(a)(4) to be misbranded under section 502 of
the FD&C Act and, if that drug is a VFD drug, also under section 504(b)
of the FD&C Act (see proposed Sec. 201.401(c)).
The proposed requirements would not apply to the labeling of
legally marketed unapproved new animal drugs for minor species that are
indexed in accordance with section 572 of the FD&C Act (see proposed
Sec. 201.401(d)(1)) or to the labeling of heritable intentional
genomic alterations in animals (see proposed Sec. 201.401(d)(2)).
The proposed requirements would not apply to promotional labeling
or advertising (see proposed Sec. 201.401(d)(3)). Promotional labeling
for new animal drugs is generally any labeling other than labeling
required in an application for a new animal drug (see Sec.
514.1(b)(3)). Materials that may be considered promotional labeling or
advertising include, for example, brochures, booklets, mailing pieces,
or reminder labeling. These materials are described in more detail for
prescription human drugs and prescription new animal drugs in existing
21 CFR 202.1.
B. Definitions (Proposed Sec. 201.403)
Proposed Sec. 201.403 would establish definitions for terms used
in proposed subpart H.
The proposed definitions for the following terms would be the same
as those already in the FD&C Act or elsewhere in the regulations:
``active ingredient''
``adverse drug experience''
``ANADA''
``drug product''
``established name''
``extralabel use''
``free-choice medicated feed''
``inactive ingredient''
``label''
``labeling''
``lot number''
``control number''
``batch number''
``NADA''
``new animal drug''
``sponsor''
``strength''
``Type A medicated article''
``Type B medicated feed''
``Type C medicated feed''
``veterinary feed directive (VFD)''
``VFD drug''
We would base the definition of ``full prescribing information''
for prescription new animal drugs on the requirements for full
prescribing information for prescription human drugs and biologics
established in Sec. 201.57(c) (21 CFR 201.57(c)).
For OTC new animal drugs, we would create a similar term, called
``full product information.'' We would define ``full product
information'' as all information necessary for the safe and effective
use of an OTC new animal drug.
We would base the definitions of other terms on the requirements
established in Sec. 201.57(c) for full prescribing information of
prescription human drugs and biologics. These terms include ``adverse
reaction,'' ``boxed warning,'' and ``contraindication.'' The proposed
definition of ``precaution'' would be based on the requirements for the
``Other special care precautions'' labeling section described in Sec.
201.57(c)(6)(ii). The proposed definition of ``warning'' would be based
on general requirements for the ``Warnings and Precautions'' section
described in Sec. 201.57(c)(6)(i).
We would define ``active moiety'' as the molecule or ion, excluding
those appended portions of the molecule that cause the drug to be an
ester, salt (including a salt with hydrogen or coordination bonds), or
other noncovalent derivative (such as a complex, chelate, or clathrate)
of the molecule, responsible for the physiological or pharmacological
action of the drug substance.
We would define ``field study'' as a type of adequate and well-
controlled study designed to assess the effectiveness and/or safety of
a new animal drug in the target animal under conditions that closely
approximate the actual conditions of use.
The term ``indication'' would mean ``the use for which the new
animal drug is approved or conditionally approved.''
We would define ``milk discard time'' as the interval between the
time of the last administration of a new animal drug and the time when
the milk can be safely consumed.
We would define ``residue warning statement'' as a statement that
warns against the use of the new animal drug in animals for which the
withdrawal period and/or milk discard time has not been determined,
and/or provides other information to prevent illegal drug residues in
food products from animals treated with the new animal drug.
The term ``target animal'' would mean the species, or collection of
species, of animals, and if applicable, the specific subset(s) of
animals (e.g., life stage, production class, age, gender) for which the
new animal drug is approved or conditionally approved. Particularly for
food-producing animals, new animal drugs may be approved for use only
during a specific life stage (e.g., growing, pregnant, lactating),
production class (e.g., growing beef steers and heifers fed in
confinement for slaughter, broiler chickens, finishing pigs), age, or
gender of the animal.
We would define ``environmental warning'' as a warning that
identifies any potential hazard to the human environment associated
with the use of the new animal drug. We would define ``user safety
warning'' as a warning that identifies any serious adverse reaction or
potential hazard to human health associated with human exposure during
use of a new animal drug via contact, inhalation, ingestion, injection,
or by other means.
The term ``withdrawal period'' would mean the interval between the
time of the last administration of a new animal drug and the time when
the animal can be safely slaughtered for food.
The proposed regulations would provide definitions for terms
associated with key labeling components for new animal drugs, including
``immediate container,'' ``package insert,'' ``secondary container,''
``small label,'' ``shipping labeling,'' ``representative Type B
medicated feed labeling,'' and ``representative Type C medicated feed
labeling.''
C. General Requirements (Proposed Sec. 201.404)
The proposed rule would require the labeling for approved or
conditionally approved new animal drugs to conform to an application
approved under section 512 of the FD&C Act or conditionally approved
under section 571 of the FD&C Act (see proposed Sec. 201.404(a)(1)).
The proposed rule would require the labeling to be informative and
accurate and neither promotional in tone nor false or misleading in any
particular and would require the labeling to be updated if new
information becomes available to cause the labeling to become
inaccurate, false, or misleading, in accordance with Sec. 514.8 of
this chapter (see proposed Sec. 201.404(a)(2) and (3)).
The proposed rule would require labeling conforming to this subpart
to be submitted to FDA per the earliest applicable compliance date
provided in the schedule, unless Sec. 201.404(b), (c), or (d) was
applicable (see proposed Sec. 201.404(a)(4)). See also section VI for
[[Page 18269]]
discussion of Proposed Effective/Compliance Dates.
Labeling included in NADAs, CNADAs, or supplements to NADAs or
CNADAs subject to Sec. 514.8(c)(2) that are submitted to FDA for
approval more than 180 days after the effective date of any final rule
based on this proposed rule would be required to conform to the
regulations as part of the application (see proposed Sec.
201.404(a)(4)(i)).
The proposed rule would require sponsors with NADAs, CNADAs, or
supplements to NADAs or CNADAs subject to Sec. 514.8(c)(2) that are
pending with FDA on the effective date of any final rule based on this
proposed rule, or submitted within 180 days after the effective date of
any final rule based on this proposed rule, to submit conforming
labeling as part of the application or supplemental application, or
alternatively, as a supplement to the approved application or
supplemental application within 180 days after the approval date of the
application or supplemental application, as determined by FDA (see
proposed Sec. 201.404(a)(4)(ii)).
The proposed rule would establish a timeline for submission of
supplements with conforming labeling for marketed new animal drugs
originally approved before the effective date of any final rule based
on this proposed rule, based on NADA number (see proposed Sec.
201.404(a)(4)(iii) through (vii)).
For an ANADA that references a new animal drug for which the NADA
has been voluntarily withdrawn for reasons other than safety or
effectiveness, or that references a new animal drug for which the NADA
has been withdrawn on the basis of one or more grounds included under
section 512(e) of the FD&C Act and the ANADA's approval was not
affected by the withdrawal, the labeling for such an ANADA would be
required to be submitted between the [effective date of a final rule
plus 1 year] and the [effective date of a final rule plus 2 years] (see
proposed Sec. 201.404(a)(4)(iii)). For an ANADA that references a new
animal drug for which the NADA has not been withdrawn, consistent with
current practice, we expect that the sponsor of such a generic new
animal drug will submit a supplemental application to the ANADA to
conform the labeling of the generic new animal drug with the revised
labeling of the RLNAD once the labeling of the RLNAD has been revised
in accordance with the schedule in proposed Sec. 201.404.
Sponsors of proprietary Type B or Type C medicated feeds for which
the underlying data and labeling are maintained in a VMF would be
required to submit conforming labeling to the VMF within 180 days after
all conforming labeling has been approved for the NADA or CNADA that is
the approved or conditionally approved source of the new animal drug
used to manufacture the proprietary medicated feed (see proposed Sec.
201.404(b)).
The labeling for new animal drugs conditionally approved before the
effective date of a final rule would not be required to comply with
proposed subpart H until an application for full approval is submitted
unless a supplement subject to Sec. 514.8(c)(2) is submitted to the
CNADA after the effective date of a final rule (see proposed Sec.
201.404(c)). The conditional approval is valid for 1 year and can be
renewed annually for up to a total of 5 years by the sponsor showing
active progress towards demonstrating substantial evidence of
effectiveness. The conditional approval will be terminated if
substantial evidence of effectiveness is not demonstrated (section
571(d) of the FD&C Act).
The proposed rule would also establish an alternative schedule for
submitting conforming labeling for combination new animal drugs
intended for use in animal feed or drinking water and approved, on or
before the effective date of a final rule, in accordance with section
512(d)(4) of the FD&C Act, i.e., per the Animal Drug Availability Act
(ADAA) of 1996. Section 512(d)(4) was amended as part of the Minor Use
Minor Species (MUMS) Act of 2004 to clarify that only products approved
under section 512(b)(1) of the FD&C Act can be used in ADAA
combinations. Thus, ADAA combination new animal drugs exclude
conditionally approved drugs subject to section 571 of the FD&C Act.
These ADAA combination new animal drugs generally provide for more than
one approved new animal drug (as a Type A medicated article) to be
mixed into medicated feed or drinking water. These ADAA combination new
animal drug approvals result in new representative (``Blue Bird'')
labeling for medicated feeds containing the combination (see proposed
Sec. 201.409).
Representative labeling for medicated feed containing the approved
combination of new animal drugs includes information from the approved
labeling for the individual drugs. Thus, it would be appropriate that
the labeling for individual drugs included in the combination be
updated to conform to any final regulations before representative
labeling for the feeds containing the combination approval is updated.
However, the ADAA combination approval would occur after the individual
drugs are approved; therefore, the NADA number for the combination
approval would be higher than the NADA numbers for the individual new
animal drugs. Thus, according to the schedule proposed in Sec.
201.404(a)(4), the conforming labeling for a combination approval would
likely need to be submitted before the conforming labeling for the
individual drugs in the combination. To address this problem, the
proposed rule would require the conforming labeling for the combination
new animal drug to be submitted within 180 days of the approval of all
conforming labeling for the individual new animal drugs used in the
combination (see proposed Sec. 201.404(d)).
The range of NADA numbers provided as ``breakpoints'' in the
proposed schedule for the submission of conforming labeling are
intended to provide for a relatively uniform number of labeling
supplements during each 1-year interval. The schedule would require
more recently approved new animal drugs to conform to the requirements
first because they are more likely to be consistent with the new
requirements than the labeling of older new animal drugs. Sponsors of
older new animal drug applications would have a longer amount of time
to comply with the new requirements. Table 1 provides these NADA ranges
in the first column. Table 1 provides in the second column the number
of currently approved and marketed NADAs within the ranges of NADAs
calculated by FDA as of September 2023 and adjusts for ADAA combination
new animal drugs that would need to conform after all individual new
animal drugs in the combination have conformed (see proposed Sec.
201.404(d)). The first row of the second column of table 1 includes
ANADAs that reference a new animal drug for which the NADA has been
voluntarily withdrawn for reasons other than safety or effectiveness,
or that reference a new animal drug for which the NADA has been
withdrawn on the basis of one or more of the grounds included under
section 512(e) of FD&C Act and for which the ANADA's approval was not
affected by the withdrawal. Table 1 also provides in the third column
the number of currently approved and marketed ANADAs with a RLNAD that
has not been withdrawn, as calculated by FDA as of September 2023;
these ANADAs are included in the row that corresponds to the NADA
number for the RLNAD.
[[Page 18270]]
Table 1--Number of Affected Applications as of September 2023 \1\
----------------------------------------------------------------------------------------------------------------
ANADA with a
NADA Nos. NADA RLNAD \2\ Total
----------------------------------------------------------------------------------------------------------------
N-141-300 +; certain ANADAs..................................... \3\ 104 9 113
N-141-000 to N-141-299.......................................... 101 86 187
N-115-000 to N-140-999.......................................... 105 87 192
N-045-000 to N-114-999.......................................... 116 68 184
N-000-001 to N-044-999.......................................... 86 66 152
-----------------------------------------------
Total....................................................... 512 316 828
----------------------------------------------------------------------------------------------------------------
\1\ These numbers will be updated in a final rule.
\2\ These are ANADAs with a RLNAD that has not been withdrawn, and they are in the row that corresponds to the
NADA number for the RLNAD.
\3\ This number includes six ANADAs that reference a withdrawn NADA.
The proposed rule would provide direction for situations in which
it may not be clear how a requirement in subpart H applies to a
particular new animal drug, or whether it applies. FDA approves and
conditionally approves new animal drugs for many species of animals.
For some new animal drugs, certain sections or subsections of labeling
required by proposed subpart H would not be applicable. For example,
new animal drugs approved or conditionally approved for use in non-
food-producing animals (e.g., cats, dogs) would not require the
labeling subsection entitled either ``Withdrawal Periods and Residue
Warnings'' or ``Withdrawal Periods''. As another example, certain new
animal drugs may not have contraindications. We would make the final
determination in these situations as to the applicability of
requirements in subpart H to specific new animal drugs (see proposed
Sec. 201.404(e)).
In addition, some sections in subpart H propose different options
to meet the labeling requirements. For example, proposed Sec.
201.405(b) would provide various options for presenting the
``Indications for Use'' section on the label for a prescription new
animal drug, depending on size of the label. In those situations where
the most appropriate option is not clear, we would make the final
determination (see proposed Sec. 201.404(e)). Ordinarily, such
determinations would be made during the review of the new animal drug
and its labeling.
When sponsors would submit labeling for purposes of conforming to
the requirements of proposed subpart H according to the schedule in
proposed Sec. 201.404(a)(4), the proposed rule would require all
labeling components for an approved or conditionally approved new
animal drug to be provided in one submission. FDA would refuse to file
labeling submissions intended to conform to this subpart that are
incomplete. This would ensure that the content and format is consistent
across all the labeling components for a particular new animal drug.
Also, this would enable FDA to review and compare all labeling
components at the same time to ensure that they conform to the proposed
regulations when finalized (see proposed Sec. 201.404(f)).
The proposed rule would establish general requirements for the
format of labeling of approved or conditionally approved new animal
drugs in proposed Sec. 201.404(g). The format and content of labeling
for prescription new animal drugs, OTC new animal drugs, or new animal
drugs for use in animal feeds would be required to comply with the
general requirements in proposed Sec. 201.404(g), as applicable, in
addition to format and content specific requirements for each type of
new animal drug (see proposed Sec. Sec. 201.405, 201.407, or 201.409,
respectively).
The proposed rule would establish requirements for the placement,
size, and prominence of the established name relative to the
proprietary name for approved or conditionally approved prescription
new animal drugs in proposed Sec. 201.404(g)(1). These requirements
are in accordance with Sec. 201.10(g)(1) and (2) (21 CFR 210.10(g)(1)
and (2)) and section 502(e)(1)(B) of the FD&C Act.
The proposed rule would establish requirements for the placement,
size, and prominence of the established name relative to the
proprietary name of approved or conditionally approved OTC new animal
drugs and labeling for approved or conditionally approved new animal
drugs for use in animal feeds, excluding representative Type B and Type
C medicated feed labeling (see proposed Sec. 201.404(g)(2)).
The proposed rule would provide the requirements for the placement,
size, and prominence of the established name on representative Type B
and Type C medicated feed labeling for approved or conditionally
approved new animal drugs for use in animal feeds (see proposed Sec.
201.404(g)(3)).
The proposed rule would require labeling text to be easy to read
and with letters that do not touch. For certain text on labeling for
new animal drugs, we believe that black text on a white background and
use of a single type style is the easiest to read. Accordingly, the
proposed rule would require that the running text, section headings,
and subsection headings of package inserts must be in black type and on
a white background and use a single type style because package inserts
provide full prescribing information for prescription new animal drugs
and full product information for OTC new animal drugs. Black text on a
white background also would be required for representative labeling for
Type B and C medicated feeds. For all other labeling components for new
animal drugs, other color combinations would be allowed, provided that
there is sufficient contrast between text and the background colors to
ensure readability. See proposed Sec. 201.404(g)(4) and (5).
The proposed rule would establish requirements for presentation of
graphics and designs on labeling for approved or conditionally approved
new animal drugs (see proposed Sec. 201.404(g)(6)). Representative
labeling for Type B and C medicated feeds would not be permitted to
have logos, graphics, or designs other than illustrations or tables
that FDA determines are necessary for proper use of the medicated feed.
This proposed format is consistent with the purpose of representative
labeling for Type B and C medicated feeds for use as template labeling
and is also consistent with the format of representative labeling for
Type B and C medicated feeds currently used in the medicated feeds
industry. The proposed rule would require the presentation of graphics
and designs on other labeling components for approved or conditionally
approved new animal drugs to comply with Sec. 201.15(b)(1) (21
[[Page 18271]]
CFR 201.15(b)(1)) and proposed Sec. 201.404(a)(2) (see proposed Sec.
201.404(g)(6)). If graphics are incorporated into the background of
these labeling components, for any text appearing over the graphics
there would need to be sufficient contrast between the text and the
graphics colors to ensure readability of the text. The use of
compressed arrows on labeling would be limited to the subsection
entitled either ``Withdrawal Periods and Residue Warnings'' or
``Withdrawal Periods,'' in accordance with the requirements in proposed
Sec. 201.404(g)(8) (see proposed Sec. 201.404(g)(6)).
The proposed rule would establish minimum letter height or type
size requirements that would vary for each labeling component and
ensure appropriate space on each component while maintaining
readability of text (see proposed Sec. 201.404(g)(7)).
Section headings and subsection headings would be required to be in
bold type that prominently distinguishes them from other approved
labeling information. Section headings would be required to be left
justified or centered, whereas subsection headings would be required to
be left justified. An exception would be the subsection of labeling
entitled either ``Withdrawal Periods and Residue Warnings'' or
``Withdrawal Periods,'' in which the subsection heading, and the
contents of the subsection, would be required to be centered within
compressed arrows (see proposed Sec. 201.404(g)(8)).
The proposed rule would require that, if the National Drug Code is
included on labeling of new animal drugs, then it must appear in
accordance with 21 CFR 207.33 (see proposed Sec. 201.404(h)).
The proposed rule would require all words, statements, and other
information on the labeling for approved or conditionally approved new
animal drugs to appear in English. In addition, the proposed rule would
also establish requirements for additional foreign language
translations of new animal drug labeling (see proposed Sec.
201.404(i)).
For approved or conditionally approved prescription new animal
drugs, the proposed rule would require that if any section or wording
of a labeling component is translated into a foreign language, the
entire full prescribing information would also be required to be
translated into the foreign language. In certain situations, FDA may
also require additional wording on other labeling components for the
prescription new animal drug to be translated into the foreign
language. These requirements would ensure that all information
necessary for the safe and effective use of the prescription new animal
drug would be provided in the foreign language (see proposed Sec.
201.404(i)(1)).
For approved or conditionally approved OTC new animal drugs, the
proposed rule would require that if any section or wording of a
labeling component is translated into a foreign language, the entire
full product information would also be required to be translated into
the foreign language. In certain situations, FDA may also require
additional wording on other labeling components for the OTC new animal
drug to be translated into the foreign language. These requirements
would ensure that all information necessary for the safe and effective
use of the OTC new animal drug would be provided in the foreign
language (see proposed Sec. 201.404(i)(2)).
For approved or conditionally approved new animal drugs for use in
animal feeds, the proposed rule would require that if the labeling
contains any representation in a foreign language, all labeling must
also appear in the foreign language (see proposed Sec. 201.404(i)(3)).
For all situations where labeling for new animal drugs is
translated into a foreign language, the translated wording would be
required to comply with the format and content requirements for
prescription, OTC, or new animal drugs for use in animal feeds in
proposed Sec. 201.405(a), Sec. 201.407(a), or Sec. 201.409,
respectively.
FDA may limit the number of languages into which labeling
information is translated to ensure clarity of information and the safe
and effective use of the new animal drug. This proposed limitation
would avoid multipage labeling in multiple languages. We intend for
this limitation to reduce medication errors and reduce the time needed
to locate information on labeling (see proposed Sec. 201.404(i)(4)).
The proposed rule would allow the predominant language to be
substituted for English on the labeling for new animal drugs
distributed solely in the Commonwealth of Puerto Rico or in a Territory
where the predominant language is other than English. We may determine
that such new animal drugs may be altogether exempt from the
requirements in proposed Sec. 201.404(i) (see proposed Sec.
201.404(j)).
D. Content and Format for Prescription (Rx) New Animal Drug Labeling--
Overview (Proposed Sec. 201.405)
The proposed rule provides content and format requirements for all
components of labeling for approved or conditionally approved
prescription (Rx) new animal drugs. Proposed Sec. 201.405 would not
apply to approved or conditionally approved new animal drugs intended
for use in or on animal feed under the professional supervision of a
licensed veterinarian because, in accordance with section 504(a) of the
FD&C Act, such drugs are approved or conditionally approved as VFD
drugs. Proposed Sec. 201.409 would establish the content and format
requirements for all components of labeling for approved or
conditionally approved new animal drugs intended for use in animal
feeds that are subject to part 558, including VFD drugs.
The proposed rule would require that labeling sections or
subsections that do not apply be omitted from the labeling for approved
or conditionally approved Rx new animal drugs (see proposed Sec.
201.405). For example, Rx new animal drugs approved or conditionally
approved for use in non-food-producing animals (e.g., cats, dogs) would
not require the labeling subsection entitled either ``Withdrawal
Periods and Residue Warnings'' or ``Withdrawal Periods''.
FDA determines the final content of each applicable section of
labeling during the review of each new animal drug as part of the
approval process.
Full prescribing information for Rx new animal drugs would include
all information necessary for safe and effective use of the Rx new
animal drug. Thus, all approved or conditionally approved Rx new animal
drugs would be required to provide a labeling component that includes
full prescribing information. The proposed rule would identify the
information that would be required to be included on the labeling
component that would provide full prescribing information for Rx new
animal drugs. If a package insert is provided with an Rx new animal
drug, the proposed rule would require the package insert to include
full prescribing information. If only partial information is provided
on a package insert, the user may mistakenly assume the package insert
includes complete information on the safe and effective use of the drug
when in fact it does not. If no package insert is provided with an Rx
new animal drug, the secondary container labeling would be required to
include full prescribing information (see proposed Sec. 201.405(a)).
The label is the labeling component that appears on the immediate
container, which is the container in contact with the drug. The
proposed rule would establish content and format requirements for the
label for an approved or conditionally approved Rx new animal drug (see
proposed Sec. 201.405(b)) and for a small label for an
[[Page 18272]]
approved or conditionally approved Rx new animal drug that FDA
determines lacks sufficient space to comply with proposed Sec.
201.405(b) (see proposed Sec. 201.405(c)).
For purposes of proposed subpart H, the proposed rule would define
a package insert for an approved or conditionally approved Rx new
animal drug as a labeling component that contains full prescribing
information and is included with the immediate container or secondary
container or is attached to the label (see proposed Sec. 201.403).
Where the package insert is attached to the label, which is sometimes
referred to as, for example, ``extended labeling,'' ``onserts,'' or
``outserts,'' for purposes of proposed subpart H, the package insert
providing full prescribing information and attached to the label would
need to comply with proposed Sec. 201.405(a). The label would need to
comply with proposed Sec. 201.405(b) or (c), as applicable.
FDA considers the secondary container for a new animal drug to be
the packaging that surrounds the immediate container. The proposed rule
would establish content and format requirements for secondary container
labeling for an approved or conditionally approved Rx new animal drug
(see proposed Sec. 201.405(d)). If a package insert is provided with
an Rx new animal drug, then the secondary container labeling would be
required to comply with proposed Sec. 201.405(d), and the package
insert would be required to provide full prescribing information to
comply with proposed Sec. 201.405(a). If no package insert is provided
with an Rx new animal drug, the proposed rule would require full
prescribing information to appear on the secondary container labeling
(see proposed Sec. 201.405(a)).
In accordance with the definition of ``label'' in section 201(k) of
the FD&C Act, information on the label must also appear on an outside
container or wrapper of the retail package, if it exists, or be easily
legible through the outside container or wrapper. For purposes of these
proposed regulations, FDA considers the secondary container to be an
``outside container or wrapper of the retail package'' for new animal
drugs. Therefore, if a secondary container exists, the proposed rule
would require the secondary container labeling to include all
information that would be on the label in accordance with proposed
Sec. 201.405(b) or (c), unless the information on the label is easily
legible through the secondary container (see proposed Sec. 201.405(a)
and (d)).
Shipping labeling is associated with the outermost carton
containing a new animal drug, which is intended for shipping, but not
displaying the product. The proposed rule would establish content and
format requirements for the shipping labeling of approved or
conditionally approved Rx new animal drugs, including a requirement
that such shipping labeling identify the new animal drug, the
manufacturer, and drug storage and handling information. However,
approved or conditionally approved Rx new animal drugs that are
controlled substances would not include information that identifies the
drug, in accordance with Sec. 1301.74(e) (21 CFR 1301.74(e)), to guard
against storage or in-transit losses (see proposed Sec. 201.405(e)).
Depending on how a sponsor intends to sell or display an approved
or conditionally approved Rx new animal drug, there may be other
containers such as display cartons and multiple unit (multi-unit)
cartons that contain immediate containers or secondary containers.
These containers may be packaged in shipping cartons. The proposed rule
would establish content and format requirements for the labeling of
these other containers for Rx new animal drugs (see proposed Sec.
201.405(f)).
Labeling sections and subsections for Rx new animal drugs would not
be numbered. Headings of sections and subsections that would be
required to appear verbatim on labeling are identified in the proposed
regulations in quotations. Similarly, certain other labeling text would
be required to appear verbatim on labeling; this text is also
identified in the proposed regulations in quotations.
The proposed rule would require the labeling of approved or
conditionally approved Rx new animal drugs to comply with other
applicable requirements in proposed subpart H (see proposed Sec.
201.405).
1. Labeling Providing Full Prescribing Information (Proposed Sec.
201.405(a))
FDA uses the term ``full prescribing information'' to identify all
information necessary for the safe and effective use of approved or
conditionally approved Rx new animal drugs. The proposed rule would
establish content and format requirements for the component of labeling
that provides full prescribing information for approved or
conditionally approved Rx new animal drugs (see proposed Sec.
201.405(a)).
If a package insert is provided with an approved or conditionally
approved Rx new animal drug, the proposed rule would require the
package insert to include full prescribing information (see proposed
Sec. 201.405(a)). If a package insert is provided with an approved or
conditionally approved Rx new animal drug, any secondary container
labeling would be required to comply with proposed Sec. 201.405(d).
If a package insert is not provided with an approved or
conditionally approved Rx new animal drug, then secondary container
labeling would be required, and the secondary container labeling would
be required to provide full prescribing information (see proposed Sec.
201.405(a)). If full prescribing information is provided on the
secondary container labeling, in accordance with section 201(k) of the
FD&C Act, proposed Sec. 201.405(a) would allow the secondary container
labeling to exclude any portions of full prescribing information that
would be required to appear on the label if such information is easily
legible through the secondary container (see proposed in Sec.
201.405(d)).
The proposed rule would require the following information to be
presented in full prescribing information for approved or conditionally
approved Rx animal drugs and in the following order:
a. Drug product identification. The proposed rule would require
this section of full prescribing information to include the proprietary
name of the finished drug product and the established name of the drug
product. If not included as part of the established name of the drug
product, the route(s) of administration and dosage form of the finished
drug product would be required to be included in this section as well
(see proposed Sec. 201.405(a)(1)(i) through (iv)).
The established name and strength or concentration of each active
ingredient would also be required. The strength or concentration of
each active ingredient would be allowed to be excluded from full
prescribing information provided on a package insert if the package
insert applies to multiple strengths or concentrations for the same Rx
new animal drug (see proposed Sec. 201.405(a)(1)(v)).
If FDA determines that identifying the pharmacological class of an
Rx new animal drug on labeling would be helpful in facilitating its
safe and effective use by the prescribing veterinarian, the proposed
rule would require that the pharmacological class be included in this
section of full prescribing information (see proposed Sec.
201.405(a)(1)(vi)).
For Rx new animal drugs that are controlled substances, symbols
provided in part 1302 (21 CFR part
[[Page 18273]]
1302) to identify the controlled substance schedule would also appear
in this section of full prescribing information. See proposed Sec.
201.405(a)(1)(vii).
Prescription statement. The proposed rule would require this
section of full prescribing information to include the prescription
statement, ``Caution: Federal law restricts this drug to use by or on
the order of a licensed veterinarian.'' Prescription new animal drugs
are limited to use under the professional supervision of a licensed
veterinarian (section 503(f)(1)(A) of the FD&C Act). The prescription
statement would indicate that the Rx new animal drug is restricted to
use by or under the order of a licensed veterinarian. Including the
prescription statement on full prescribing information would be
consistent with its inclusion on the label for Rx new animal drugs,
which is required by section 503(f)(4) of the FD&C Act. The requirement
for including the prescription statement as part of full prescribing
information is proposed under the authority granted to FDA under
sections 502(a), 201(n), and 701(a) of the FD&C Act. See proposed Sec.
201.405(a)(2).
c. Conditional approval statement. For conditionally approved Rx
new animal drugs, the proposed rule would require this section of full
prescribing information to include, in accordance with section
571(f)(1)(A) of the FD&C Act, the statement indicating conditional
approval by FDA and the application number: ``conditionally approved by
FDA pending a full demonstration of effectiveness under application
number [insert number]''. This statement would be required to be
prominent and conspicuous (see proposed Sec. 201.405(a)(3)).
d. Boxed warnings. For Rx new animal drugs requiring boxed
warnings, the proposed rule would require this section of full
prescribing information to include the boxed warnings. Boxed warnings
convey the most significant risks associated with the use of a Rx new
animal drug. If applicable to the product, they would appear at this
prominent location. An upper case ``WARNING'' heading would be included
in the box, and the box, heading, and contents would be bolded. The
boxed warning would be brief, with reference to more detailed
information in other sections of full prescribing information if
applicable (see proposed Sec. 201.405(a)(4)).
e. Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use, in accordance with Sec. 530.41
(21 CFR 530.41), the proposed rule would require this section of full
prescribing information to include an extralabel use prohibition
statement that begins with the phrase: ``Federal law prohibits the
extralabel use of this drug . . .'' and concludes with a description of
the prohibition as described in Sec. 530.41 (see proposed Sec.
201.405(a)(5)). For example, ``Federal law prohibits the extralabel use
of this drug in lactating dairy cows.''
Certain new animal drugs are prohibited from extralabel use in some
or all animals, in accordance with Sec. 530.41. This information is
critical for inclusion on labeling. If a user fails to comply with an
extralabel use prohibition statement, there could be serious safety
consequences for the target animal, or in the case of a food-producing
animal, also for humans consuming food derived from the target animal.
f. ``Description.'' The proposed rule would require this section of
full prescribing information to have the heading ``Description,''
followed by a description of the new animal drug. The description would
include the proprietary name of the finished drug product and
established name of the drug product, and the route(s) of
administration and dosage form if not included as part of the
established name. The description would also include identifying
characteristics of the dosage form, such as color, shape, coating,
scoring, and imprinting. All approved and available strengths or
concentrations of the new animal drug to which full prescribing
information applies would need to be identified in this section of full
prescribing information. If the drug product was sterile, this fact
would also be identified in this section of full prescribing
information (see proposed Sec. 201.405(a)(6)).
The established name of each inactive ingredient would be required
to be included in the ``Description'' section of full prescribing
information. The proposed rule would require all inactive ingredients
to be listed in decreasing order of predominance, by weight or
concentration (see proposed Sec. 201.405(a)(6)(viii)). FDA believes
that listing inactive ingredients in decreasing order of predominance
based on either weight or concentration would provide the most
clinically useful information to users.
In accordance with section 502(e)(1)(A)(iii) of the FD&C Act, the
proposed rule would not require the listing of inactive ingredients on
full prescribing information under circumstances that would result in
disclosure of trade secret information. Therefore, where sponsors
believe the listing of inactive ingredients on product labeling would
result in disclosure of trade secret information, they would be able to
request exemption from this labeling requirement under proposed Sec.
201.411. If an exemption from the listing of inactive ingredients to
avoid divulgence of trade secret information is granted under Sec.
201.411, this section of full prescribing information would be required
to state: ``Certain inactive ingredients are not listed to avoid
disclosing trade secret information.'' (see proposed Sec.
201.405(a)(6)(viii)(A)).
Section 502(e)(1)(B) of the FD&C Act allows an exemption from
listing inactive ingredients on the label of Rx drugs if doing so would
be impracticable. The current regulations at Sec. 201.105(b)(5) for Rx
animal drugs state that names of flavorings, perfumes, certain color
additives, and ``trace amounts of harmless substances added solely for
individual product identification'' may be exempt from listing on the
labels for products other than for oral use. The regulations at Sec.
201.105 predate the requirements in section 502(e)(1)(B) of the FD&C
Act and are outdated. The proposed rule would replace the requirements
for labels for approved or conditionally approved Rx new animal drugs
currently provided in Sec. 201.105(b) with the requirements in
proposed Sec. 201.405(b) and (c) (see discussion in section V.D.2. and
3). Thus, the labels for approved or conditionally approved Rx new
animal drugs would no longer qualify for the exemptions currently
identified in Sec. 201.105(b)(5).
If under proposed Sec. 201.411 FDA grants an exemption from
listing inactive ingredients because their listing would be
impracticable, this section of full prescribing information would need
to state the following: ``Certain inactive ingredients are not listed
because their listing would be impracticable.'' (see proposed Sec.
201.405(a)(6)(viii)(B)).
g. ``Indications for Use.'' This section of full prescribing
information would be required to have the heading ``Indications for
Use,'' followed by the approved or conditionally approved indication(s)
and target animal(s) in the following format: ``For [indication(s)] in
[target animal(s)]'' (see proposed Sec. 201.405(a)(7)(i)).
Consistent with regulations for the labeling of Rx human products
in Sec. 201.57(c)(2)(i)(A), if a Rx new animal drug is approved or
conditionally approved for use only under specific conditions, e.g., in
conjunction with a primary mode of therapy, special diet, surgery,
behavioral modification, or some other drug, the proposed rule
[[Page 18274]]
would require that this information be specified in the ``Indications
for Use'' section of full prescribing information (see proposed Sec.
201.405(a)(7)(ii)).
If, in approving or conditionally approving an application, FDA
requires, for safety and/or effectiveness reasons, a statement(s) on
labeling identifying animals for which the Rx new animal drug has not
been approved or conditionally approved, the proposed rule would
require that statement(s) to appear in the ``Indications for Use''
section of full prescribing information (see proposed Sec.
201.405(a)(7)(iii)). We currently require the statement(s) proposed in
Sec. 201.405(a)(7)(iii) to appear on labeling of some approved new
animal drugs, particularly new animal drugs for use in food-producing
animals, to clarify the target animal for which the drug is approved.
The statements are typically required if we determine that unapproved
use of a drug in animals similar to the target animal(s) is reasonably
foreseeable and we believe that inclusion of such a statement on the
labeling of the new animal drug could increase the safe and effective
use of the drug. For example, feedlot beef cattle are not intended to
provide milk for human consumption. Therefore, we will not likely
require an evaluation of the human food safety of a new animal drug in
lactating dairy cows if the new animal drug is only to be approved for
use in feedlot cattle. However, we will often require a statement on
labeling that the drug is not for use in lactating dairy cows intended
to produce milk for human consumption to avoid use of the drug in this
unapproved and unevaluated manner.
The statement(s) proposed in Sec. 201.405(a)(7)(iii) is not
intended to prohibit extralabel use of approved new animal drugs
allowed under specific circumstances, in accordance with section
512(a)(4) of the FD&C Act and part 530 (21 CFR part 530), but would
help to clarify that some specific uses are extralabel and have not
been evaluated for safety and effectiveness by FDA. Currently, there is
no uniform place on the labeling for new animal drugs for such
statements to appear. If we require such statements on labeling to
ensure safe and effective use of a new animal drug, the proposed rule
would require the statements to be placed within the ``Indications for
Use'' section of full prescribing information. Inclusion of such
statements in the ``Indications for Use'' section would not necessarily
preclude also including similar statements in other sections or
subsections of full prescribing information if warranted. For example,
it may be appropriate to include a similar statement as a residue
warning statement in the ``Withdrawal Periods and Residue Warnings''
subsection to expand upon human food safety risks of the extralabel use
of the new animal drug in animals other than the target animal.
h. ``Dosage and Administration.'' The proposed rule would require
this section of full prescribing information to have the heading
``Dosage and Administration,'' followed by the dosage and
administration information for the new animal drug for each indication
and target animal (see proposed Sec. 201.405(a)(8)).
Sometimes FDA requires additional labeling for Rx new animal drugs
that provides important information for the animal owner or person
treating the animal. If such additional labeling is required, the
proposed ``Dosage and Administration'' section of full prescribing
information would advise the veterinarian to provide the additional
labeling to the animal owner or person treating the animal (see
proposed Sec. 201.405(a)(8)(i)).
The remainder of this section of full prescribing information would
be required to include information necessary for treatment of the
animal with the Rx new animal drug in accordance with FDA approval or
conditional approval, including: route(s) of administration and
specific site(s) of administration, if applicable; dose or dose range;
intervals between doses, if applicable; and duration of treatment. For
some injectable products, FDA may require a statement of the maximum
volume per injection site to facilitate the drug's safe and effective
use, and the proposed rule would require this information to be
included in this section of full prescribing information. Also, certain
animal populations may require modifications to the dosage and
administration for safe and effective use. These modifications would be
required to appear in this section of full prescribing information.
Other required dosage and administration information would also be
included in this section of full prescribing information. See proposed
Sec. 201.405(a)(8).
i. ``Contraindications.'' For Rx new animal drugs with
contraindications, the proposed rule would require this section of full
prescribing information to have the heading ``Contraindications,''
followed by the contraindications (see proposed Sec. 201.405(a)(9)).
As defined in proposed Sec. 201.403, a contraindication would include
any situation in which the new animal drug should not be used because
the risk of use clearly outweighs any possible benefit to the animal
and includes only known hazards.
j. ``Warnings and Precautions.'' The proposed rule would require
this section of full prescribing information for all approved or
conditionally approved Rx new animal drugs, and it would have the
heading ``Warnings and Precautions'' (see proposed Sec.
201.405(a)(10)). As defined in proposed Sec. 201.403, warnings would
describe any serious adverse reactions or potential hazards associated
with the use of the new animal drug. In addition, precautions would be
defined as any special care to be exercised for safe and effective use
of the new animal drug, which may include recommended screening,
monitoring, or diagnostic tests. Multiple subsections, if applicable,
would be included in the ``Warnings and Precautions'' section of full
prescribing information as described below and in the following order,
and the warnings and precautions would be provided in the applicable
subsection:
i. ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods.'' All Rx new animal drugs approved or conditionally approved
for use in food-producing animals would be required to have as the
first subsection of the ``Warnings and Precautions'' section of full
prescribing information a subsection entitled either ``Withdrawal
Periods and Residue Warnings'' or ``Withdrawal Periods'' (see proposed
Sec. 201.405(a)(10)(i)). This subsection would provide all human food
safety warnings, including milk discard times, withdrawal periods, and
residue warning statements, as applicable to the new animal drug.
As defined in proposed Sec. 201.403, a withdrawal period is the
interval between the time of the last administration of a new animal
drug and the time when the animal can be safely slaughtered for food.
Withdrawal periods apply to all food-producing animals. As defined in
proposed Sec. 201.403, a milk discard time is the interval between the
time of the last administration of a new animal drug and the time when
the milk can be safely consumed. Milk discard times apply to female
animals that produce milk for human consumption. A new animal drug
approved for use in female animals that produce milk for human
consumption may have both a milk discard time and a withdrawal period.
As defined in proposed Sec. 201.403, a residue warning statement
warns against the use of the new animal drug in animals for which the
withdrawal period and/or milk discard time has not been determined,
and/or provides other
[[Page 18275]]
information to prevent illegal drug residues in food products from
animals treated with the new animal drug.
If there are any residue warning statements for the new animal
drug, the proposed rule would require this subsection of full
prescribing information to have the title ``Withdrawal Periods and
Residue Warnings.'' If there are no residue warning statements
associated with the new animal drug, this subsection of full
prescribing information would be required to have the title
``Withdrawal Periods'' (see proposed Sec. 201.405(a)(10)(i)(A)).
If the new animal drug is approved or conditionally approved for
use in food-producing animals excluding female animals that produce
milk for human consumption, the proposed rule would require this
subsection of full prescribing information to include the withdrawal
period(s) followed by any residue warning statements (see proposed
Sec. 201.405(a)(10)(i)(B)).
If the new animal drug is approved or conditionally approved for
use in food-producing animals excluding female animals that produce
milk for human consumption and there is no withdrawal period, the
proposed rule would require this subsection of full prescribing
information to state, ``No withdrawal period is required when used
according to labeling.'' This statement would be followed by any
residue warnings statements (see proposed Sec. 201.405(a)(10)(i)(C)).
If the new animal drug is approved or conditionally approved for
use in female animals that produce milk for human consumption, the
proposed rule would require this subsection of full prescribing
information to include the milk discard time(s), followed by the
withdrawal period(s), followed by any residue warning statements (see
proposed Sec. 201.405(a)(10)(i)(D)).
If the new animal drug is approved or conditionally approved for
use in female animals that produce milk for human consumption, and
there is a milk discard time(s) but no withdrawal period, the proposed
rule would require this subsection of full prescribing information to
include the milk discard time(s), followed by the statement, ``No
withdrawal period is required when used according to labeling.'' This
statement would be followed by any residue statements (see proposed
Sec. 201.405(a)(10)(i)(E)).
If the new animal drug is approved or conditionally approved for
use in female animals that produce milk for human consumption and there
is no milk discard time but there is a withdrawal period(s), the
proposed rule would require this subsection of full prescribing
information to include the withdrawal period(s), followed by the
statement, ``No milk discard time is required when used according to
labeling.'' This statement would be followed by any residue warnings
statements (see proposed Sec. 201.405(a)(10)(i)(F)).
If the new animal drug is approved or conditionally approved for
use in female animals that produce milk for human consumption and there
is no milk discard time and no withdrawal period, the proposed rule
would require this subsection of full prescribing information to state,
``No milk discard time and no withdrawal period is required when used
according to labeling.'' This statement would be followed by any
residue warnings statements (see proposed Sec. 201.405(a)(10)(i)(G)).
Currently, new animal drugs approved for use in food-producing
animals that have no milk discard time and/or withdrawal period may or
may not indicate this information on labeling. If this information is
not provided on labeling, potentially it could be confusing to the user
of the new animal drug as to whether or not there is a milk discard
time or withdrawal period for the new animal drug. Requiring this
subsection of full prescribing information for all new animal drugs
approved or conditionally approved for use in food-producing animals,
and requiring a statement, if appropriate, to indicate that there is no
milk discard time or withdrawal period when the new animal drug is used
according to labeling, will better ensure the safe use of animal drugs
in food-producing animals.
To further highlight for users this critical subsection of full
prescribing information, the title of this subsection and all
information in this subsection would be required to be centered and
placed entirely within compressed arrows, in accordance with proposed
Sec. 201.404(g)(8). The compressed arrows would be black for package
inserts, or a color that clearly contrasts from background colors for
other approved labeling (see proposed Sec. 201.405(a)(10)(i)(A)).
Currently, the compressed arrows are used voluntarily, although not
consistently, on the labeling for many new animal drugs approved for
use in food-producing animals. Currently other statements not
associated with human food safety may also appear within the compressed
arrows. The proposed rule would limit the use of compressed arrows to
the subsection entitled either ``Withdrawal Periods and Residue
Warnings'' or ``Withdrawal Periods'' (see proposed Sec.
201.404(g)(6)), which would only contain human food safety information.
ii ``User Safety Warnings.'' The proposed rule would require this
subsection of the ``Warnings and Precautions'' section of full
prescribing information to have the heading ``User Safety Warnings,''
followed by the user safety warnings. As defined in proposed Sec.
201.403, a user safety warning would be a warning that identifies
serious adverse reactions or potential hazards to human health
associated with human exposure during use of a new animal drug via
contact, inhalation, ingestion, injection, or by other means. This
information would be required to prevent or decrease the risk of harm
to humans.
The first statements that would be included in this subsection of
full prescribing information are: ``Not for use in humans. Keep out of
reach of children.'' The subsection would next list all additional user
safety warnings listed in decreasing order of severity or frequency.
The final information that would be included in this subsection of full
prescribing information would be a sentence explaining how to obtain
Safety Data Sheet(s) for the drug. Chemical manufacturers,
distributors, and/or importers are required pursuant to 29 CFR
1910.1200(g) to provide Safety Data Sheets for each hazardous chemical
to downstream users to communicate information on these hazards. Safety
Data Sheets include information such as the properties of each
chemical; their physical, health, and environmental health hazards;
protective measures; and safety precautions for handling, storing, and
transporting the chemical. The sentence in this subsection of full
prescribing information would be required to be formatted as follows:
``To obtain a Safety Data Sheet(s), contact [insert name of
manufacturer] at [insert manufacturer's telephone number] or [insert
manufacturer's website].'' See proposed Sec. 201.405(a)(10)(ii).
iii. ``Animal Safety Warnings and Precautions.'' For Rx new animal
drugs with target animal safety warnings and precautions, the proposed
rule would require this subsection of the ``Warnings and Precautions''
section of full prescribing information to have the heading ``Animal
Safety Warnings and Precautions,'' followed by the target animal safety
warnings and precautions (see proposed Sec. 201.405(a)(10)(iii)).
Target animal safety warnings identify any serious adverse reactions or
potential hazards to the target animal(s) associated with the use of
the new animal drug. Precautions for Rx new
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animal drugs often include recommendations for specific screening,
monitoring, diagnostic tests, or special care that should be taken by
the prescribing veterinarian for safe and effective use of the new
animal drug (see definition in proposed Sec. 201.403). The heading of
the subsection would include the term ``animal safety warnings'', i.e.,
``Animal Safety Warnings and Precautions,'' because we believe the term
``animal safety warnings'' is more familiar to users of Rx new animal
drugs than ``target animal safety warnings.''
Precautions are sometimes difficult to distinguish from target
animal safety warnings. Currently, target animal safety warnings and
precautions are sometimes presented separately on the labeling for Rx
new animal drugs. However, because the two sets of information are
often closely related, it is advantageous to combine them into one
subsection of full prescribing information.
Warnings and precautions are combined in the ``Highlights'' and
``Full Prescribing Information'' for human Rx drugs and biologics (see
Sec. Sec. 201.56 and 57). Similarly, combining target animal safety
warnings and precautions in the ``Animal Safety Warnings and
Precautions'' subsection of full prescribing information would be less
burdensome for sponsors of Rx new animal drugs because sponsors would
not be required to distinguish one from the other.
iv. ``Environmental Warnings.'' For approved or conditionally
approved new animal drugs that have environmental warnings, the
proposed rule would require this subsection of the ``Warnings and
Precautions'' section of full prescribing information to have the
heading ``Environmental Warnings,'' followed by the environmental
warnings (see proposed Sec. 201.405(a)(10)(iv)). FDA's regulations at
21 CFR part 25 implementing the National Environmental Policy Act
(NEPA), 42 U.S.C. 4321 et seq., address the environmental impact
considerations required for products regulated by FDA, including new
animal drugs. Under NEPA, the responsible Agency official examines the
environmental risks of the proposed action and the alternative courses
of action, selects a course of action, and ensures that any necessary
mitigating measures are implemented as a condition for approving the
selected course of action (see 21 CFR 25.40(e)). In some instances,
sponsors may choose to include environmental warnings on the labeling
for their new animal drugs as a means to mitigate or reduce the
potential for environmental impacts to occur from the use or disposal
of the drug (see 21 CFR 25.45). These warnings would generally include
information to prevent or decrease the risk of any environmental
effects. The proposed rule would require any environmental warnings
applicable to the new animal drug that are included in an approved or
conditionally approved application be provided in this subsection of
full prescribing information (see proposed Sec. 201.405(a)(10)(iv)).
v. ``Other Warnings.'' For new animal drugs having warnings not
more appropriately placed in other ``Warnings and Precautions''
subsections, the proposed rule would require the last subsection of the
``Warnings and Precautions'' section of full prescribing information to
have the heading ``Other Warnings,'' followed by those warnings (see
proposed Sec. 201.405(a)(10)(v)).
k. ``Adverse Reactions.'' For Rx new animal drugs that we determine
have adverse reactions, this section of full prescribing information
would be required to have the heading ``Adverse Reactions,'' followed
by the adverse reactions (see proposed Sec. 201.405(a)(11)). Adverse
reactions would be defined in proposed Sec. 201.403 as undesirable
effects, reasonably associated with the use of the drug product, that
may occur as part of the pharmacological action of the drug or that may
be unpredictable in occurrence. The proposed rule would require this
section of full prescribing information to include adverse reactions
that occur with use of the Rx new animal drug and with use of drugs in
the same pharmacologically active and chemically related classes, if
applicable. Furthermore, we may require additional information as
necessary for the prescribing veterinarian to interpret the adverse
reactions, such as the total number of animals exposed to the drug and
the extent and nature of exposure.
The proposed rule would also require that adverse reactions be
presented within the following categories, as applicable, in decreasing
order of severity or frequency: preapproval experience, foreign market
experience known prior to U.S. approval for drugs also commercially
marketed outside of the United States, and post-approval experience
(see proposed Sec. 201.405(a)(11)). For previously approved Rx new
animal drugs for which the labeling would be updated in accordance with
the schedule provided in this rule, if the preapproval experience and/
or foreign market experience categories were not included on full
prescribing information when the drug was approved, we may allow one or
both of these subsections to be excluded from the ``Adverse Reactions''
section of full prescribing information if we determine that including
such information is not necessary to ensure the safe and effective use
of the drug. Post-approval experience would typically be added to
labeling of the drug after it has been approved in the United States
and if additional adverse drug experiences (as defined by Sec. 514.3)
associated with the use of the drug have been identified.
l. ``Contact Information.'' The proposed rule would require this
section of full prescribing information to have the heading ``Contact
Information,'' followed by the sponsor's contact information for
veterinarians or consumers to facilitate requesting additional
information or to report suspected adverse drug experiences. FDA's
contact information for voluntary reporting of adverse drug experiences
for animal drugs would also be required. Requiring contact information
on new animal drug labeling increases the likelihood that a user will
report adverse drug events to the sponsor and/or to the Center for
Veterinary Medicine (CVM). Increasing the likelihood of receiving
adverse drug event reports would allow new animal drug sponsors and CVM
to better monitor and detect emerging safety issues with approved or
conditionally approved new animal drugs on the market. Any increase in
adverse drug event reporting and monitoring resulting from this
proposed requirement would benefit both animal and human health.
The sponsor's contact information would be the name of the
manufacturer, packer, or distributor, whichever is identified in the
``Name and place of business'' section of full prescribing information
per proposed Sec. 201.405(a)(22). If more than one business is
identified in the ``Name and place of business'' section of full
prescribing information, the drug sponsor would select the most
appropriate of these businesses to use in the ``Contact Information''
section to provide additional information about the Rx new animal drug
and to contact regarding suspected adverse drug experiences.
The statements in this section of full prescribing information
would be required to be structured as follows: ``Contact [insert name
of business] at [insert business telephone number] or [insert business
web address]. To report suspected adverse drug experiences, contact
[insert name of business] at [insert business telephone number]. For
additional information about reporting adverse drug experiences for
animal drugs, contact FDA at [insert current
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FDA telephone number for voluntary reporting of adverse drug
experiences] or [insert current FDA web address for voluntary reporting
of adverse drug experiences].'' See proposed Sec. 201.405(a)(12).
Sponsors can search FDA's website or contact FDA by telephone to find
the current FDA telephone number and web address for voluntary
reporting of adverse drug experiences for animal drugs.
m. ``Information for Animal Owner.'' For Rx new animal drugs
required to have additional information to be communicated by the
prescribing veterinarian to the animal owner or person treating the
animal to ensure safe and effective use of the Rx new animal drug, the
proposed rule would require this section of full prescribing
information to have the heading ``Information for Animal Owner,''
followed by the specific information.
For some new animal drugs, FDA may determine it is necessary for
sponsors to provide the animal owner or person treating the animal with
additional labeling, such as a ``client information sheet,'' to ensure
the safe and effective use of the Rx new animal drug. If we determine
that such additional labeling is necessary, a printed copy of the
additional labeling would be required to be attached to or accompany
the package insert or secondary container labeling if no package insert
is provided. See proposed Sec. 201.405(a)(13).
n. ``Clinical Pharmacology.'' For Rx new animal drugs required to
include clinical pharmacology information on labeling, the proposed
rule would require this section of full prescribing information to have
the heading ``Clinical Pharmacology,'' followed by the clinical
pharmacology information for the Rx new animal drug in the target
animal(s). The required information would be relevant for understanding
the relationship between dose, systemic drug exposure, safety, and
clinical effectiveness. This information may help the prescribing
veterinarian to predict how the Rx new animal drug would perform in the
different animal patient populations likely to be encountered under
clinical use conditions. This section of full prescribing information
would be required to include the following three separate subsections,
as applicable to the Rx new animal drug: ``Mechanism of action,''
``Pharmacodynamics,'' and ``Pharmacokinetics'' (see proposed Sec.
201.405(a)(14)).
o. ``Microbiology.'' For antimicrobial Rx new animal drugs, the
proposed rule would require this section of full prescribing
information to have the heading ``Microbiology,'' followed by a
description of microbiologic data associated with the studies used to
support the effectiveness of the drug against the indicated pathogens.
The microbiology data would be required to be restricted to organisms
named in the approved or conditionally approved indications.
If in vitro data for antimicrobial new animal drugs are included in
this section of full prescribing information and the data have not been
correlated to clinical effectiveness, then such in vitro data would be
required to be immediately preceded by the following statement: ``The
following in vitro data are available, but their clinical significance
is unknown.'' See proposed Sec. 201.405(a)(15).
p. ``Target Animal Safety.'' The proposed rule would require this
section of full prescribing information to have the heading ``Target
Animal Safety,'' followed by a summary of the basis for the conclusion
that the new animal drug is safe in the target animal(s) when used as
approved or conditionally approved (see proposed Sec. 201.405(a)(16)).
q. ``Effectiveness.'' The proposed rule would require this section
of full prescribing information to have the heading ``Effectiveness,''
followed by a summary of the basis for the conclusion that the new
animal drug is effective in the target animal(s) when used as approved.
For conditionally approved drugs, the ``Effectiveness'' section of full
prescribing information would be required to include a summary of the
basis for the reasonable expectation of effectiveness (see proposed
Sec. 201.405(a)(17)).
r. ``Net Contents.'' The proposed rule would require this section
of full prescribing information, when presented on the secondary
container labeling, to have the heading ``Net Contents,'' followed by
the contents of the secondary container. The proposed rule would
exclude a ``Net Contents'' section from package inserts (see proposed
Sec. 201.405(a)(18)).
s. ``How Supplied.'' The proposed rule would require this section
of full prescribing information to have the heading ``How Supplied,''
followed by information on available drug strengths, concentrations,
and container sizes to which the labeling applies. The information in
this section would be required to be revised if new strengths,
concentrations, or container sizes are added (see proposed Sec.
201.405(a)(19)).
t. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of full prescribing information to have the
heading ``Storage, Handling, and Disposal'' (see proposed Sec.
201.405(a)(20)). Drug storage information would be included in this
section and may include, for example, required temperature, humidity,
and/or light exposure conditions to maintain the potency of the Rx new
animal drug until its established expiration date. Also, any handling
and drug disposal information that we determine to be necessary for
safe and effective use of the Rx new animal drug would be included in
this section. Handling information may include, for example,
recommendations to reseal reusable bottles promptly after opening and
conditions necessary to maintain potency of reconstituted new animal
drugs. Drug disposal information may include, for example, instructions
on disposal of unused portions of new animal drugs remaining after
treatment, as well as used needles and/or syringes.
u. NADA/ANADA approval statement. In accordance with section
502(w)(3) of the FD&C Act, by no later than September 30, 2023,
approved new animal drugs must include the following statement on
labeling: ``Approved by FDA under NADA # xxx-xxx''. By no later than
September 30, 2023, approved generic Rx new animal drugs must include
the following statement on labeling: ``Approved by FDA under ANADA #
xxx-xxx''. For approved Rx new animal drugs, the proposed rule would
require this section of full prescribing information to include the
``NADA approval statement,'' indicating the product's NADA number and
that it was approved by FDA. For approved generic Rx new animal drugs
that would be covered by these regulations (i.e., those that reference
an NADA that has been withdrawn for reasons other than safety or
effectiveness or under section 512(e) of the FD&C Act and the ANADA's
approval was not affected by the withdrawal), the proposed rule would
require this section of full prescribing information to include the
``ANADA approval statement.'' The proposed rule would establish format
requirements for the approval statement and would require that the
approval statement not be so prominent as to obscure other required
information. The approval statement could not be incorporated into a
seal, stamp, logo, or graphic. See proposed Sec. 201.405(a)(21).
v. Name and place of business. The proposed rule would require this
section of full prescribing information to identify the name and place
of business of the manufacturer, packer, or distributor (see proposed
Sec. 201.405(a)(22)).
w. ``Lot Number and Expiration Date.'' The proposed rule would
require
[[Page 18278]]
this section of full prescribing information when provided on the
secondary container labeling. Package inserts are excluded from this
requirement because they might apply to multiple lots of secondary or
immediate containers of the Rx new animal drug. When full prescribing
information is provided on the secondary container labeling, this
section would be required to have the heading ``Lot Number and
Expiration Date,'' followed by the identifying lot or control number of
the Rx new animal drug within the secondary container (see proposed
Sec. 201.405(a)(23)). Should a problem be reported to FDA, a lot or
control number would help us more easily to identify and trace back a
specific lot of a product. The proposed rule would also require this
section to include the expiration date of the Rx new animal drug within
the secondary container, in accordance with Sec. 201.17 (21 CFR
201.17). An expiration date better ensures that the new animal drug
would not be used after it expires.
Alternatively, the proposed rule would allow for this section of
full prescribing information to refer to the location on the secondary
container labeling or secondary container where the lot or control
number and expiration date are printed (see proposed Sec.
201.405(a)(23)). As an example, if the lot number and expiration date
are printed on the bottom flap of a secondary container, then the
secondary container labeling may state in this section, ``See carton
bottom flap for lot number and expiration date.'' However, in
accordance with Sec. 201.17, the proposed rule would allow an
expiration date to be excluded from the secondary container labeling or
secondary container if the expiration date provided on the label or
immediate container is easily legible through the secondary container.
x. ``Revision Date.'' The proposed rule would require this section
of full prescribing information to have the heading ``Revision Date,''
followed by the date of the most recent revision of the component of
labeling that provides full prescribing information, listing the month
followed by the year (see proposed Sec. 201.405(a)(24)). This
information is important to ensure that the most current approved
version of the labeling is being used.
2. Prescription New Animal Drug Label (Rx Label) (Proposed Sec.
201.405(b))
The proposed rule would establish content and format requirements
for the information presented on the label for approved or
conditionally approved Rx new animal drugs (Rx label) (see proposed
Sec. 201.405(b)). As defined in proposed Sec. 201.403, ``label'' has
the same meaning as given in section 201(k) of the FD&C Act, which
defines the term ``label'' to mean a display of written, printed, or
graphic matter upon the immediate container of any article. As defined
in proposed Sec. 201.403, the immediate container means the container
in contact with the new animal drug, and it excludes package liners.
Proposed Sec. 201.405(b) would apply to Rx labels that are of
adequate size to contain the proposed required information per that
paragraph, whereas proposed Sec. 201.405(c) would apply to small
labels for Rx new animal drugs that are not of adequate size to contain
all the proposed required information in proposed Sec. 201.405(b).
Prescription new animal drugs labels to which Sec. 201.405(b)
would apply may consist of a single panel, a front panel and one side
or back panel, or a front panel and multiple side and/or back panels,
and the proposed rule would provide for such label designs (see Sec.
201.405(b)). For Rx labels with a front panel and one side or back
panel, the proposed rule would require certain information for the
front panel (see proposed Sec. 201.405(b)(1)), and the side or back
panel (see proposed Sec. 201.405(b)(2)). For Rx labels consisting of a
single panel, the proposed rule would require the information
identified in proposed Sec. 201.405(b)(1) followed by the information
identified in proposed Sec. 201.405(b)(2), in order, on the single
panel. For Rx labels with a front panel and multiple side and/or back
panels, the information identified in proposed Sec. 201.405(b)(1)
followed by the information identified in proposed Sec. 201.405(b)(2)
would be required in order, starting on the front panel, continuing on
the panel immediately to the right of the front panel, and continuing
to fill the panels to the right until all of the information in
proposed Sec. 201.405(b)(1) and (b)(2) was presented. In all
instances, the information proposed in Sec. 201.405(b)(2)(iii) and
(iv), i.e., ``Active Ingredient'' or ``Active Ingredients'' and
``Inactive Ingredients,'' would need to appear on the same panel.
a. Front panel. The proposed rule would require the following
information to be presented on the front panel of the Rx label for an
approved or conditionally approved Rx new animal drug and in the
following order. Unless otherwise indicated, this information would be
the same as that required by proposed Sec. 201.405(a) for full
prescribing information.
i. Drug product identification. The proposed rule would require
this section of the Rx label to include drug product identification
information (see proposed Sec. 201.405(b)(1)(i)). This information may
help the user quickly and correctly identify the product and
distinguish it from other, similar products. The information included
in this section of the Rx label would include the same information as
that in the drug product identification section of full prescribing
information, as described in proposed Sec. 201.405(a)(1), in addition
to a statement that the drug product is sterile, if applicable. Full
prescribing information would require a drug product identification
section and a ``Description'' section. Full prescribing information for
sterile Rx new animal drugs would be required to identify in the
``Description'' section that the drug is sterile. However, due to space
limitations, no ``Description'' section is proposed for the Rx label.
Instead, the drug product identification section of the Rx label for
sterile Rx new animal drugs would be required to state that the drug
product is sterile. See proposed Sec. 201.405(b)(1)(i).
ii. Prescription statement. The proposed rule would require this
section of the Rx label to include the prescription statement (see
proposed Sec. 201.405(b)(1)(ii)). In accordance with section 503(f)(4)
of the FD&C Act, all Rx new animal drugs must state on the label:
``Caution: Federal law restricts this drug to use by or on the order of
a licensed veterinarian.''
iii. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the Rx
label to include a conditional approval statement, as described in
proposed Sec. 201.405(a)(3) for full prescribing information (see
proposed Sec. 201.405(b)(1)(iii)).
iv. Boxed warnings. For approved or conditionally approved Rx new
animal drugs requiring boxed warnings, the proposed rule would require
this section of the Rx label to include the boxed warnings, as
described in proposed Sec. 201.405(a)(4) for full prescribing
information (see proposed Sec. 201.405(b)(1)(iv)).
v. ``Indications for Use.'' The proposed rule would require this
section of the Rx label to have the heading ``Indications for Use,''
followed by the ``Indications for Use'' section, as described in
proposed Sec. 201.405(a)(7) for full prescribing information. If we
determine that there is insufficient space on the Rx label for the
complete ``Indications for Use'' section as described in proposed Sec.
201.405(a)(7), then the proposed rule would require
[[Page 18279]]
the sponsor to include in this section of the Rx label the statement
required in proposed Sec. 201.405(a)(7)(i), i.e., ``For
[indication(s)] in [target animal(s)]''. If there is insufficient space
on the Rx label for the statement in proposed Sec. 201.405(a)(7)(i),
then an abbreviated version of the statement would be required: ``For
[abbreviated indication(s)] in [target animal(s)]''. In either
situation where there is insufficient space on the Rx label for the
complete ``Indications for Use'' section as specified in proposed Sec.
201.405(a)(7), the required statement would be followed by one of the
following statements: ``See package insert for complete `Indications
for Use' '' if full prescribing information is provided on a package
insert; or ``See package labeling for complete `Indications for Use' ''
if full prescribing information is provided on the secondary container
labeling. See proposed Sec. 201.405(b)(1)(v).
The complete ``Indications for Use'' section as described in
proposed Sec. 201.405(a)(7) may exceed the available space on the Rx
label if, for example, it includes specific conditions of use (proposed
Sec. 201.405(a)(7)(ii)) or animals for which the new animal drug is
not approved or conditionally approved (proposed Sec.
201.405(a)(7)(iii)), and/or the indication(s) is lengthy and/or
complex. For example, a new animal drug approved to treat and control
multiple species of roundworms, lungworms, lice, and mites in beef
cattle would ordinarily identify all of those species in the
``Indications for Use'' section of the label. However, if space is
insufficient on the Rx label to provide the identity of all of the
species of the roundworms, lungworms, lice, and mites for which the
drug is effective, an acceptable ``abbreviated'' version of the
``Indications for Use'' section on the Rx label for this product might
include, for example, ``For treatment and control of certain species of
roundworms, lungworms, lice, and mites in beef cattle. See package
insert for complete `Indications for Use'.''
vi. Extralabel use prohibition statement. For approved Rx new
animal drugs prohibited from extralabel use, in accordance with Sec.
530.41, the proposed rule would require this section of the Rx label to
include the extralabel use prohibition statement, as described in
proposed Sec. 201.405(a)(5) for full prescribing information (see
proposed Sec. 201.405(b)(1)(vi)).
vii. ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods.'' For new animal drugs approved or conditionally approved for
use in food-producing animals, the proposed rule would require this
section of the Rx label to have the heading ``Withdrawal Periods and
Residue Warnings'' or ``Withdrawal Periods,'' followed by all human
food safety warnings, including milk discard times, withdrawal periods,
and residue warning statements, as described in proposed Sec.
201.405(a)(10)(i) for full prescribing information. If there is
insufficient space on the front panel of Rx labels with only a front
panel and one side or back panel, the proposed rule would require this
section to be provided on the side or back panel of the Rx label
immediately following the full prescribing information statement
specified in proposed Sec. 201.405(b)(2)(i). See proposed Sec.
201.405(b)(1)(vii).
viii. ``Net Contents.'' The proposed rule would require this
section of the Rx label to have the heading ``Net Contents,'' followed
by the contents of the immediate container, in accordance with Sec.
201.51 (see proposed Sec. 201.405(b)(1)(viii)).
ix. NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the proposed rule would require this
section of the Rx label to include the NADA or ANADA approval
statement, as described in proposed Sec. 201.405(a)(21) for full
prescribing information (see proposed Sec. 201.405(b)(1)(ix)).
b. Side or back panel. The proposed rule would require the
following information to be presented on the side or back panel of the
Rx label for an approved or conditionally approved Rx new animal drug
in the following order (see proposed Sec. 201.405(b)(2)). Unless
otherwise indicated, this information would be the same as that
required by proposed Sec. 201.405(a) for full prescribing information.
i. Full prescribing information statement. The proposed rule would
require this section of the Rx label to include one of two statements
(see proposed Sec. 201.405(b)(2)(i)). If full prescribing information
is provided on the package insert, the following statement would be
used: ``Before using this drug, read package insert for full
prescribing information.'' If full prescribing information is provided
on the secondary container labeling, the following statement would be
used: ``Before using this drug, read package labeling for full
prescribing information.'' Because full prescribing information would
not be provided on the Rx label, the purpose of the statements would be
to remind the veterinarian to read full prescribing information before
using the Rx new animal drug.
ii. ``Dosage and Administration.'' The proposed rule would require
this section of the Rx label to have the heading ``Dosage and
Administration,'' followed by the ``Dosage and Administration''
section, as described in proposed Sec. 201.405(a)(8) for full
prescribing information. If there is insufficient space on the Rx label
for the complete requirements as specified in proposed Sec.
201.405(a)(8), or if it is necessary for additional information
provided in full prescribing information that is not provided on the Rx
label to be read before administering the drug (e.g., complete warnings
and precautions, contraindications, and/or target animal safety), then
FDA may exclude this section from the Rx label (see proposed Sec.
201.405(b)(2)(ii)). For example, with respect to the latter situation,
if careful observation of the animal after dosing is advised to watch
for adverse reactions, this information typically would be described in
the ``Animal Safety Warnings and Precautions'' subsection, which would
not be required on the Rx label but would be required on full
prescribing information. Excluding the ``Dosage and Administration''
section from the Rx label in this situation helps to ensure that the
veterinarian would read full prescribing information, which would
include the ``Dosage and Administration'' section as well as the
``Animal Safety Warnings and Precautions'' subsection, before treating
the animal. Users would also be reminded to read full prescribing
information before using the drug via the full prescribing information
statement that would be required in the previous section of the Rx
label by proposed Sec. 201.405(b)(2)(i).
iii. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the Rx label to have the heading
``Active Ingredient'' or ``Active Ingredients,'' followed by the
established name and strength or concentration of each active
ingredient. If the Rx new animal drug contains one active ingredient,
the proposed rule would require this section of the Rx label to be
entitled ``Active Ingredient.'' If the Rx new animal drug contains more
than one active ingredient, the proposed rule would require this
section of the Rx label to be entitled ``Active Ingredients.'' The
requirement to provide established name and strength or concentration
of each active ingredient on the Rx label would be consistent with the
requirement for the established name and quantity or proportion of each
active ingredient on the label of prescription drugs, in
[[Page 18280]]
accordance with section 502(e)(1)(A)(ii), (B), and (g) of the FD&C Act
(see proposed Sec. 201.405(b)(2)(iii)). This information is currently
required to be on the label for Rx animal drugs, in accordance with
Sec. 201.105(b)(4). Proposed Sec. 201.405(b) and (c) would establish
the content and format requirements for the label for approved or
conditionally approved Rx new animal drugs and would replace the
requirements for the label of approved or conditionally approved Rx new
animal drugs currently provided in Sec. 201.105(b). Furthermore, Sec.
201.105 would be amended to refer to proposed Sec. 201.405 for the
content and format requirements for labeling components for approved or
conditionally approved Rx new animal drugs.
iv. ``Inactive Ingredients.'' The proposed rule would require this
section of the Rx label to have the heading ``Inactive Ingredients,''
followed by the established name of each inactive ingredient, as
described in proposed Sec. 201.405(a)(6)(viii) for full prescribing
information (see proposed Sec. 201.405(b)(2)(iv)).
v. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the Rx label to have the heading ``Storage,
Handling, and Disposal,'' followed by drug storage, handling, and
disposal information, as described in proposed Sec. 201.405(a)(20) for
full prescribing information (see proposed Sec. 201.405(b)(2)(v)).
vi. Name and place of business. The proposed rule would require
this section of the Rx label to identify the name and place of business
of the manufacturer, packer, or distributor, as required in section
502(b) of the FD&C Act (see proposed Sec. 201.405(b)(2)(vi)).
vii. ``Lot Number and Expiration Date'' or ``Lot Number.'' The
proposed rule would require this section of the Rx label to have the
heading ``Lot Number and Expiration Date'' or ``Lot Number,'' followed
by the identifying lot or control number of the Rx new animal drug
within the immediate container (see proposed Sec. 201.405(b)(2)(vii)).
A lot or control number would allow us to more easily identify and
trace back a specific lot of a product should a problem be reported to
FDA. We would also require this section of the Rx label to include the
expiration date of the Rx new animal drug within the immediate
container, in accordance with Sec. 201.17.
An expiration date on the Rx label better ensures that the new
animal drug would not be used after it expires. Alternatively, the
proposed rule would allow for this section to refer to the location on
the Rx label or immediate container where the lot or control number and
expiration date are printed (see proposed Sec. 201.405(b)(2)(vii)). As
an example, if the lot number and expiration date are printed at the
top of the immediate container, then the Rx label may state in this
section, ``See top of container for lot number and expiration date.''
If the immediate container provides a single dose of the Rx new animal
drug and is packaged individually in a secondary container that
provides an expiration date on the secondary container labeling or
secondary container, the proposed rule would not require an expiration
date on the Rx label or immediate container, in accordance with Sec.
201.17. Under such provision, this section of the Rx label would be
required to be entitled ``Lot Number.''
viii. ``Revision Date.'' The proposed rule would require the last
section of the Rx label to have the heading ``Revision Date,'' followed
by the date of the most recent revision of the Rx label, listing the
month followed by the year (see proposed Sec. 201.405(b)(2)(viii)).
3. Prescription New Animal Drug Small Label (Rx Small Label) (Proposed
Sec. 201.405(c))
The proposed rule would establish content and format requirements
for the small label for Rx new animal drugs (Rx small label) (see
proposed Sec. 201.405(c)). Some immediate containers, such as blister
packs, pre-filled syringes, and small vials, are so small that only a
minimal amount of information can be included on their label. The
proposed rule would establish requirements for Rx small labels for
approved or conditionally approved Rx new animal drugs (see proposed
Sec. 201.405(c)). We recognize that the size of the label is dependent
upon the size of the immediate container. If an immediate container
lacks sufficient space to contain a label that accommodates all of the
information required by proposed Sec. 201.405(b), the requirements of
proposed Sec. 201.405(c) would instead apply. We would ordinarily make
this determination during the review of the new animal drug and its
labeling, taking into consideration the readability and legibility of
the information.
The proposed rule would require the following information to be
presented on the Rx small label for an approved or conditionally
approved Rx new animal drug and in the following order (see proposed
Sec. 201.405(c)).
a. Proprietary name of the finished drug product. The proposed rule
would require this section of the Rx small label to include the
proprietary name of the finished drug product (see proposed Sec.
201.405(c)(1)). This requirement already exists for small labels for
drugs in general in Sec. 201.10(i)(1), but is repeated in these
proposed regulations to include all requirements for labeling of
approved or conditionally approved new animal drugs in proposed subpart
H.
b. Established name of the drug product. The proposed rule would
require this section of the Rx small label to include the established
name of the drug product (see proposed Sec. 201.405(c)(2)). This
requirement already exists for small labels for drugs in general in
Sec. 201.10(i)(1), but is repeated in these proposed regulations to
include all requirements for labeling of approved or conditionally
approved new animal drugs in proposed subpart H.
c. Active ingredient(s). The proposed rule would require this
section of the Rx small label to include the established name and
strength or concentration of each active ingredient, which is
consistent with the requirement for the established name and quantity
or proportion of each active ingredient on the label of prescription
drugs, in accordance with section 502(e)(1)(A)(ii), (B), and (g) of the
FD&C Act (see proposed Sec. 201.405(c)(3)). This information is
currently required to be on the label for Rx animal drugs, in
accordance with Sec. 201.105(b)(4).
Proposed Sec. 201.405(b) and (c) would establish the content and
format requirements for the label for approved or conditionally
approved Rx new animal drugs and would replace the requirements for the
label of approved or conditionally approved Rx new animal drugs
currently provided in Sec. 201.105(b). Furthermore, Sec. 201.105
would be amended to cross-reference proposed Sec. 201.405 for the
content and format requirements for labeling components for approved or
conditionally approved Rx new animal drugs (see discussion in section
V.I.).
d. Controlled substance symbol. For Rx new animal drugs that are
controlled substances, the proposed rule would require this section of
the Rx small label to include the controlled substance schedule symbol
in accordance with part 1302 designating the schedule for the drug
substance (see proposed Sec. 201.405(c)(4)).
e. Prescription statement. The proposed rule would require this
section of the Rx small label to state: ``Rx Animal Use'' (see proposed
Sec. 201.405(c)(5)). In accordance with section 503(f)(4) of the FD&C
Act, the label for all Rx new animal drugs must include the following
statement: ``Caution: Federal law restricts this drug to use by or on
the order of a licensed
[[Page 18281]]
veterinarian.'' However, since 1960 (25 FR 12592) Sec. 201.105(b)(6)
exempts ``containers too small or otherwise unable to accommodate a
label with sufficient space'' to include the full prescription
statement provided that the full statement may be placed on the outer
container only. We are proposing the ``Rx Animal Use'' statement for a
Rx small label for Rx new animal drugs. This statement would
appropriately identify the Rx status of the new animal drug and would
require minimal space.
f. ``For [target animal(s)] only.'' The proposed rule would require
this section of the Rx small label to include a brief listing of the
approved target animal(s) as follows: ``For [target animal(s)] only''
(see proposed Sec. 201.405(c)(6)). The brief listing of the approved
target animal(s) would be used in place of full ``Indications for Use''
information because Rx small labels lack sufficient space. This listing
would not require as much space on the Rx small label.
g. Full prescribing information statement. The proposed rule would
require this section of the Rx small label to include one of two
statements. If full prescribing information is provided on the package
insert, the following statement would be used: ``Read package insert
for full prescribing information.'' If full prescribing information is
provided on the secondary container labeling, the following statement
would be used: ``Read package labeling for full prescribing
information.'' See proposed Sec. 201.405(c)(7). Because full
prescribing information would not be provided on the Rx small label,
the purpose of the statements would be to remind the veterinarian to
read full prescribing information before using the Rx new animal drug.
h. ``Net Contents.'' The proposed rule would require this section
of the Rx small label to have the heading ``Net Contents,'' followed by
the contents of the immediate container, in accordance with Sec.
201.51 (see proposed Sec. 201.405(c)(8)).
i. Name and place of business. The proposed rule would require this
section of the Rx small label to identify the name and place of
business of the manufacturer, packer, or distributor, as required in
section 502(b) of the FD&C Act (see proposed Sec. 201.405(c)(9)).
j. ``Lot, Exp. and Storage'' or ``Lot and Storage.'' The proposed
rule would require this section of the Rx small label to have the
heading ``Lot, Exp. and Storage'' or ``Lot and Storage,'' followed by
the identifying lot or control number of the Rx new animal drug within
the immediate container (see proposed Sec. 201.405(c)(10)). Should a
problem be reported to FDA, a lot or control number would allow us more
easily to identify and trace back a specific lot of a product. We would
also require this section of the Rx small label to include the
expiration date of the Rx new animal drug within the immediate
container, in accordance with Sec. 201.17. An expiration date on the
Rx small label better ensures that the new animal drug would not be
used after it expires.
The proposed rule would also require this section of the Rx small
label to include drug storage information for the new animal drug (see
proposed Sec. 201.405(c)(10)). Storage information is necessary to
maintain potency of the drug before its expiration date. Requiring this
information on the Rx small label is needed for safe and effective use
of new animal drugs. If the immediate container provides a single dose
of the Rx new animal drug and is packaged individually in a secondary
container that provides an expiration date on the secondary container
labeling or secondary container, the proposed rule would not require an
expiration date on the Rx small label or immediate container, in
accordance with Sec. 201.17. Under such provision, this section of the
Rx small label would be required to be entitled ``Lot and Storage.''
k. ``Revision Date.'' The proposed rule would require this section
of the Rx small label to have the heading ``Revision Date,'' followed
by the date of the most recent revision of the Rx small label, listing
the month followed by the year (see proposed Sec. 201.405(c)(11)).
4. Labeling for Secondary Containers for Rx New Animal Drugs That
Include a Package Insert (Rx Secondary Container Labeling) (Proposed
Sec. 201.405(d))
The proposed rule would establish content and format requirements
for the information on the labeling for secondary containers of
approved or conditionally approved Rx new animal drugs that include a
package insert (Rx secondary container labeling) (see proposed Sec.
201.405(d)). In this situation, the package insert would be required to
include full prescribing information, as described in proposed Sec.
201.405(a).
In accordance with section 201(k) of the FD&C Act, the Rx secondary
container labeling could exclude any information described in proposed
Sec. 201.405(d) that would be required to appear on the Rx label or Rx
small label (see proposed Sec. 201.405(b) or (c), respectively) if
such information on the Rx label or Rx small label was easily legible
through the secondary container.
The Rx secondary container labeling to which proposed Sec.
201.405(d) would apply may consist of a front panel and one side or
back panel, or a front panel and multiple side and/or back panels.
Proposed Sec. 201.405(d) would provide for such Rx secondary container
labeling designs. For Rx secondary container labeling with a front
panel and one side or back panel, proposed Sec. 201.405(d)(1) would
provide required information for the front panel, and proposed Sec.
201.405(d)(2) would provide required information for the side or back
panel. For Rx secondary container labeling with a front panel and
multiple side and/or back panels, the information identified in
proposed Sec. 201.405(d)(1) followed by the information identified in
proposed Sec. 201.405(d)(2) would be required in order, starting on
the front panel, continuing on the panel immediately to the right of
the front panel, and continuing to fill the panels to the right until
all of the information in proposed Sec. 201.405(d)(1) and (d)(2) was
presented. In all instances, the information proposed in Sec.
201.405(d)(2)(v) and (vi), i.e., ``Active Ingredient'' or ``Active
Ingredients'' and ``Inactive Ingredients,'' would need to appear on the
same panel.
a. Front panel. The proposed rule would require the following
information to be presented on the front panel of the Rx secondary
container labeling and in the following order (see proposed Sec.
201.405(d)(1)). Unless otherwise indicated, this information would be
the same as that required by proposed Sec. 201.405(a) for full
prescribing information.
i. Drug product identification. The proposed rule would require
this section of the Rx secondary container labeling to include drug
product identification (see proposed Sec. 201.405(d)(1)(i)). The
information would be the same as that included in the drug product
identification section for full prescribing information, as described
in proposed Sec. 201.405(a)(1), and would also identify if the drug
product is sterile. Full prescribing information would require a drug
product identification section and a ``Description'' section. Full
prescribing information for sterile Rx new animal drugs would be
required to identify in the ``Description'' section that the drug is
sterile. However, due to space limitations, no ``Description'' section
would be required on the Rx secondary container labeling. Instead, the
drug product identification section of the Rx secondary container
labeling for sterile Rx new animal drugs would be required to state
that the drug is sterile.
ii. Prescription statement. The proposed rule would require this
section of the Rx secondary container
[[Page 18282]]
labeling to include the prescription statement, as described in
proposed Sec. 201.405(a)(2) for full prescribing information (see
proposed Sec. 201.405(d)(1)(ii)).
iii. Conditional approval statement. For conditionally approved Rx
new animal drugs, the proposed rule would require this section of the
Rx secondary container labeling to include a conditional approval
statement, as described in proposed Sec. 201.405(a)(3) for full
prescribing information (see proposed Sec. 201.405(d)(1)(iii)).
iv. Boxed warnings. For approved or conditionally approved Rx new
animal drugs requiring boxed warnings, the proposed rule would require
this section of the Rx secondary container labeling to include the
boxed warnings, as described in proposed Sec. 201.405(a)(4) for full
prescribing information (see proposed Sec. 201.405(d)(1)(iv)).
v. ``Indications for Use.'' The proposed rule would require this
section of the Rx secondary container labeling to have the heading
``Indications for Use,'' followed by the ``Indications for Use''
section, as described in proposed Sec. 201.405(a)(7) for full
prescribing information (see proposed Sec. 201.405(d)(1)(v)).
vi. Extralabel prohibition statement. For approved new animal drugs
prohibited from extralabel use, in accordance with Sec. 530.41, the
proposed rule would require this section of the Rx secondary container
labeling to include the extralabel use prohibition statement, as
described in proposed Sec. 201.405(a)(5) for full prescribing
information (see proposed Sec. 201.405(d)(1)(vi)).
vii. ``Net Contents.'' The proposed rule would require this section
of the Rx secondary container labeling to have the heading ``Net
Contents,'' followed by the contents of the secondary container (see
proposed Sec. 201.405(d)(1)(vii)).
viii. NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the proposed rule would require
this section of the Rx secondary container labeling to include the NADA
or ANADA approval statement, as described in proposed Sec.
201.405(a)(21) for full prescribing information (see proposed Sec.
201.405(d)(1)(viii)).
b. Side or back panel. The proposed rule would require the
following information to be presented on the side or back panel of the
Rx secondary container labeling and in the following order (see
proposed Sec. 201.405(d)(2)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information.
i. Full prescribing information statement. The proposed rule would
require this section of the Rx secondary container labeling to include
the statement: ``Before using this drug, read package insert for full
prescribing information'' (see proposed Sec. 201.405(d)(2)(i)).
Because full prescribing information would not be provided on the Rx
secondary container labeling, the purpose of the full prescribing
information statement would be to remind the veterinarian to read full
prescribing information before using the Rx new animal drug.
ii. ``Dosage and Administration.'' The proposed rule would require
this section of the Rx secondary container labeling to have the heading
``Dosage and Administration,'' followed by the ``Dosage and
Administration'' section, as described in proposed Sec. 201.405(a)(8)
for full prescribing information (see proposed Sec.
201.405(d)(2)(ii)).
iii. ``Contraindications.'' The proposed rule would require this
section of the Rx secondary container labeling to have the heading
``Contraindications,'' followed by the ``Contraindications'' section,
as described in proposed Sec. 201.405(a)(9) for full prescribing
information (see proposed Sec. 201.405(d)(2)(iii)).
iv. ``Warnings and Precautions.'' The proposed rule would require
this section of the Rx secondary container labeling to have the heading
``Warnings and Precautions,'' followed by the ``Warnings and
Precautions'' section, as described in proposed Sec. 201.405(a)(10)
for full prescribing information (see proposed Sec.
201.405(d)(2)(iv)).
v. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the Rx secondary container labeling
to have the heading ``Active Ingredient'' or ``Active Ingredients,''
followed by the established name and strength or concentration of each
active ingredient, as described in proposed Sec. 201.405(b)(2)(iii)
for the Rx label (see proposed Sec. 201.405(d)(2)(v)).
vi. ``Inactive Ingredients.'' The proposed rule would require this
section of the Rx secondary container labeling to have the heading
``Inactive Ingredients,'' followed by the established name of each
inactive ingredient, as described in proposed Sec. 201.405(a)(6)(viii)
for full prescribing information (see proposed Sec.
201.405(d)(2)(vi)).
vii. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the Rx secondary container labeling to have the
heading ``Storage, Handling, and Disposal,'' followed by drug storage,
handling, and disposal information, as described in proposed Sec.
201.405(a)(20) for full prescribing information (see proposed Sec.
201.405(d)(2)(vii)).
viii. Name and place of business. The proposed rule would require
this section of the Rx secondary container labeling to identify the
manufacturer, packer, or distributor, as described in proposed Sec.
201.405(a)(22) for full prescribing information (see proposed Sec.
201.405(d)(2)(viii)).
ix. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the Rx secondary container labeling to have the
heading ``Lot Number and Expiration Date,'' followed by the identifying
lot or control number of the Rx new animal drug within the secondary
container. The proposed rule would also require this section of the Rx
secondary container labeling to include the expiration date of the Rx
new animal drug within the secondary container, in accordance with
Sec. 201.17. Alternatively, the proposed rule would allow for this
section to refer to the location on the Rx secondary container labeling
or secondary container where the lot or control number and expiration
date are printed (see proposed Sec. 201.405(d)(2)(ix)). As an example,
if the lot number and expiration date are printed on the bottom flap of
a secondary container, then the labeling may state in this section,
``See carton bottom flap for lot number and expiration date. However,
in accordance with Sec. 201.17, the proposed rule would allow an
expiration date to be excluded from the Rx secondary container labeling
or secondary container if the expiration date provided on the Rx label,
Rx small label, or immediate container is easily legible through the
secondary container.
x. ``Revision Date.'' The proposed rule would require this section
of the Rx secondary container labeling to have the heading ``Revision
Date,'' followed by the date of the most recent revision of the Rx
secondary container labeling, listing the month followed by the year
(see proposed Sec. 201.405(d)(2)(x)).
5. Shipping Labeling for Rx New Animal Drugs (Rx Shipping Labeling)
(Proposed Sec. 201.405(e))
The proposed rule would establish content and format requirements
for the information on the shipping labeling for approved or
conditionally approved Rx new animal drugs (Rx shipping labeling). As
defined in proposed Sec. 201.403, shipping labeling is associated with
the outermost carton containing immediate containers, secondary
containers, and/or multiple
[[Page 18283]]
unit (multi-unit) cartons of a new animal drug and intended for
shipment, but not display, of the product. The proposed rule would
require the Rx shipping labeling to include, among additional
information, drug product identity, the manufacturer, packer, or
distributor, and drug storage and handling conditions (see proposed
Sec. 201.405(e)). However, the Rx shipping labeling for controlled
substances would not include information that would identify the drug,
in accordance with Sec. 1301.74(e), to guard against storage or in-
transit losses due to theft or diversion.
The proposed rule would require the following information to be
presented on the Rx shipping labeling and in the following order (see
proposed Sec. 201.405(e)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information.
a. Proprietary name of the finished drug product. The proposed rule
would require this section of the Rx shipping labeling to include the
proprietary name of the finished drug product (see proposed Sec.
201.405(e)(1)). This section would be excluded from the Rx shipping
labeling for a controlled substance.
b. Established name of the drug product. The proposed rule would
require this section of the Rx shipping labeling to include the
established name of the drug product (see proposed Sec.
201.405(e)(2)). This section would be excluded from the Rx shipping
labeling for a controlled substance.
c. Established name and strength or concentration of each active
ingredient. The proposed rule would require this section of the Rx
shipping labeling to provide the established name and strength or
concentration of each active ingredient. This section would be excluded
from the Rx shipping labeling for a controlled substance (see proposed
Sec. 201.405(e)(3)).
d. Conditional approval statement. For conditionally approved Rx
new animal drugs, the proposed rule would require this section of the
Rx shipping labeling to include a conditional approval statement, as
described in proposed Sec. 201.405(a)(3) for full prescribing
information (see proposed Sec. 201.405(e)(4)). This section would be
excluded from the Rx shipping labeling for a controlled substance.
e. ``Net Contents.'' The proposed rule would require this section
of the Rx shipping labeling to have the heading ``Net Contents,''
followed by the contents of the shipping carton (see proposed Sec.
201.405(e)(5)).
f. ``Storage and Handling.'' The proposed rule would require this
section of the Rx shipping labeling to have the heading ``Storage and
Handling,'' followed by drug storage information (see proposed Sec.
201.405(e)(6)). Also, any handling information required for safe and
effective use of the new animal drug would be included in this section.
Information on disposal of the new animal drug would not be required to
be included on the Rx shipping labeling.
g. NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the proposed rule would require this
section of the Rx shipping labeling to include the NADA or ANADA
approval statement, as described in proposed Sec. 201.405(a)(21) for
full prescribing information (see proposed Sec. 201.405(e)(7)). This
section would be excluded from the Rx shipping labeling for a
controlled substance.
h. Name and place of business. The proposed rule would require this
section of the Rx shipping labeling to identify the name and place of
business of the manufacturer, packer, or distributor, as described in
proposed Sec. 201.405(a)(22) for full prescribing information (see
proposed Sec. 201.405(e)(8)).
i. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the Rx shipping labeling to have the heading
``Lot Number and Expiration Date,'' followed by the identifying lot or
control number(s) and the expiration date(s) of the Rx new animal drug
within the shipping carton (see proposed Sec. 201.405(e)(9)). The
shipping carton may contain more than one lot of the new animal drug,
and therefore, more than one lot or control number and expiration date
may be listed in this section of the Rx shipping labeling.
j. ``Revision Date.'' The proposed rule would require the last
section of the Rx shipping labeling to have the heading ``Revision
Date,'' followed by the date of the most recent revision of the Rx
shipping labeling, listing the month followed by the year (see proposed
Sec. 201.405(e)(10)).
6. Other Approved Labeling for Rx New Animal Drugs (Rx Other Approved
Labeling) (Proposed Sec. 201.405(f))
The proposed rule would establish content and format requirements
for the information presented on other approved labeling for approved
or conditionally approved Rx new animal drugs (Rx other approved
labeling) (see proposed Sec. 201.405(f)). Rx other approved labeling
includes, but is not limited to, labeling on display cartons and multi-
unit cartons (excluding shipping cartons), containing the immediate
containers or the secondary containers of the Rx new animal drug.
The proposed rule would require the following information to be
presented on the Rx other approved labeling and in the following order
(see proposed Sec. 201.405(f)). Unless otherwise indicated, this
information would be the same as required by proposed Sec. 201.405(a)
for full prescribing information.
a. Proprietary name of the finished drug product. The proposed rule
would require this section of the Rx other approved labeling to include
the proprietary name of the finished drug product (see proposed Sec.
201.405(f)(1)).
b. Established name of the drug product. The proposed rule would
require this section of the Rx other approved labeling to include the
established name of the drug product (see proposed Sec.
201.405(f)(2)).
c. Established name and strength or concentration of each active
ingredient. The proposed rule would require this section of the Rx
other approved labeling to provide the established name and strength or
concentration of each active ingredient (see proposed Sec.
201.405(f)(3)).
d. Controlled substance symbol. The proposed rule would require
this section of the Rx other approved labeling for controlled
substances to include the controlled substance schedule symbol, in
accordance with part 1302 designating the schedule for the drug
substance (see proposed Sec. 201.405(f)(4)).
e. Prescription statement. The proposed rule would require this
section of the Rx other approved labeling to include the prescription
statement, as described in proposed Sec. 201.405(a)(2) for full
prescribing information (see proposed Sec. 201.405(f)(5)).
f. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the Rx
other approved labeling to include a conditional approval statement, as
described in proposed Sec. 201.405(a)(3) for full prescribing
information (see proposed Sec. 201.405(f)(6)).
g. Boxed warnings. For approved or conditionally approved Rx new
animal drugs requiring boxed warnings, the proposed rule would require
this section of the Rx other approved labeling to include the boxed
warnings, as described in proposed Sec. 201.405(a)(4) for full
prescribing information (see proposed Sec. 201.405(f)(7)).
[[Page 18284]]
h. Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use, in accordance with Sec. 530.41,
the proposed rule would require this section of the Rx other approved
labeling to include the extralabel use prohibition statement, as
described in proposed Sec. 201.405(a)(5) for full prescribing
information (see proposed Sec. 201.405(f)(8)).
i. ``Net Contents.'' The proposed rule would require this section
of the Rx other approved labeling to have the heading ``Net Contents,''
followed by the contents of the container to which the Rx other
approved labeling applies (see proposed Sec. 201.405(f)(9)).
j. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the Rx other approved labeling to have the
heading ``Storage, Handling, and Disposal,'' followed by drug storage,
handling, and disposal information, as described in proposed Sec.
201.405(a)(20) for full prescribing information (see proposed Sec.
201.405(f)(10)).
k. NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the proposed rule would require this
section of the Rx other approved labeling to include the NADA or ANADA
approval statement, as described in proposed Sec. 201.405(a)(21) for
full prescribing information (see proposed Sec. 201.405(f)(11)).
l. Name and place of business. The proposed rule would require this
section of the Rx other approved labeling to identify the name and
place of business of the manufacturer, packer, or distributor, as
described in proposed Sec. 201.405(a)(22) for full prescribing
information (see proposed Sec. 201.405(f)(12)).
m. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the Rx other approved labeling to have the
heading ``Lot Number and Expiration Date,'' followed by the identifying
lot or control number of the Rx new animal drug within the container to
which the Rx other approved labeling applies. This section of the Rx
other approved labeling would also be required to include the
expiration date of the Rx new animal drug within the container to which
the Rx other approved labeling applies, in accordance with Sec.
201.17. In accordance with Sec. 201.17, the proposed rule would allow
an expiration date to be excluded from the Rx other approved labeling
if the expiration date provided on containers within or their labeling
is easily legible through the container to which the Rx other approved
labeling applies (see proposed Sec. 201.405(f)(13)).
n. ``Revision Date.'' The proposed rule would require the last
section of the Rx other approved labeling to have the heading
``Revision Date,'' followed by the date of the most recent revision of
the Rx other approved labeling, listing the month followed by the year
(see proposed Sec. 201.405(f)(14)).
E. Content and Format for Over-The-Counter (OTC) New Animal Drug
Labeling--Overview (Proposed Sec. 201.407)
The proposed rules provides content and format requirements for all
components of labeling for approved or conditionally approved OTC new
animal drugs other than those for use in animal feeds that are subject
to part 558 (see proposed Sec. 201.407). Proposed Sec. 201.409 would
establish the content and format requirements for all components of
labeling for approved or conditionally approved new animal drugs
intended for use in animal feeds that are subject to part 558. OTC new
animal drugs are new animal drugs that can be used without a
prescription from a veterinarian. They are intended for use by the
layperson, such as pet owners and livestock producers. In accordance
with section 502(f) of the FD&C Act, OTC drugs must bear adequate
directions for use on labeling. Adequate directions for use means
directions under which the layperson can use a drug safely and for the
purposes for which it is intended (see Sec. 201.5).
The proposed rule would require that labeling sections or
subsections that do not apply be omitted from the labeling for approved
or conditionally approved OTC new animal drugs (see proposed Sec.
201.407). For example, OTC new animal drugs approved or conditionally
approved for use in non-food-producing animals (e.g., cats, dogs) would
not require the labeling subsection entitled either ``Withdrawal
Periods and Residue Warnings'' or ``Withdrawal Periods''.
FDA determines the final content of each applicable section of
labeling during the review of each new animal drug as part of the
approval process.
The proposed rule would identify the information that would be
required to be included on the labeling component that would provide
full product information for OTC new animal drugs in proposed Sec.
201.407(a). Full product information for OTC new animal drugs would be
similar in concept to full prescribing information for Rx new animal
drugs in that it would include all information necessary for the safe
and effective use of the OTC new animal drug. Thus, all approved or
conditionally approved OTC new animal drugs would be required to
provide a labeling component that includes full product information. If
a package insert is provided with an OTC new animal drug, the proposed
rule would require the package insert to include full product
information. If only partial information is provided on a package
insert, the user may mistakenly assume the package insert includes
complete information on the safe and effective use of the drug when in
fact it does not. If no package insert is provided with an OTC new
animal drug, the secondary container labeling would be required to
include full product information. If no package insert or secondary
container labeling is provided with the OTC new animal drug, then full
product information would need to be provided on the label (see
proposed Sec. 201.407(a)).
The label is the labeling component that appears on the immediate
container, which is the container in contact with the drug. The
proposed rule would establish content and format requirements for the
label for an approved or conditionally approved OTC new animal drug
that does not provide full product information (see proposed Sec.
201.407(b)). The proposed rule would establish content and format
requirements for a small label for an approved or conditionally
approved OTC new animal drug that we determine lacks sufficient space
to comply with proposed Sec. 201.407(b) (see proposed Sec.
201.407(c)).
For purposes of proposed subpart H, we would define a package
insert for an approved or conditionally approved OTC new animal drug as
a labeling component that contains full product information and is
included with the immediate container or secondary container or is
attached to the label (see proposed Sec. 201.403). Where the package
insert is attached to the label, which is sometimes referred to as, for
example, ``extended labeling,'' ``onserts,'' or ``outserts,'' for
purposes of proposed subpart H, the package insert providing full
product information and attached to the label would need to comply with
proposed Sec. 201.407(a). The label would need to comply with proposed
Sec. 201.407(b) or (c), as applicable.
FDA considers the secondary container for a new animal drug to be
the packaging that surrounds the immediate container. The proposed rule
would establish content and format requirements for secondary container
labeling for an approved or conditionally approved OTC new animal drug
(see proposed Sec. 201.407(d)). If a package insert is provided with
an OTC new animal drug, then the secondary container labeling would be
[[Page 18285]]
required to comply with proposed Sec. 201.407(d) and the package
insert would be required to provide full product information to comply
with proposed Sec. 201.407(a). If no package insert is provided with
an OTC new animal drug, the proposed rule would require full product
information to appear on the secondary container labeling (see proposed
Sec. 201.407(a)).
In accordance with the definition of ``label'' in section 201(k) of
the FD&C Act, information on the label must also appear on an outside
container or wrapper of the retail package, if it exists, or be easily
legible through the outside container or wrapper. For purposes of these
proposed regulations, FDA considers the secondary container to be an
``outside container or wrapper of the retail package'' for new animal
drugs. Therefore, if a secondary container exists, the proposed rule
would require the secondary container labeling to include all
information that would be on the label in accordance with proposed
Sec. 201.407(b) or (c), unless the information on the label is easily
legible through the secondary container (see proposed Sec. 201.407(a)
or (d)).
Shipping labeling is associated with the outermost carton
containing a new animal drug, which is intended for shipping, but not
displaying the product. The proposed rule would establish content and
format requirements for the shipping labeling of approved or
conditionally approved OTC new animal drugs including a requirement
that such shipping labeling identify the new animal drug, the
manufacturer, and drug storage and handling information(see proposed
Sec. 201.407(e)).
Depending on how a sponsor intends to sell or display an approved
or conditionally approved OTC new animal drug, there may be other
containers such as display cartons and multiple unit (multi-unit)
cartons that contain immediate containers or secondary containers.
These containers may be packaged in shipping cartons. The proposed rule
would establish content and format requirements for the labeling of
these other containers for OTC new animal drugs (see proposed Sec.
201.407(f)).
Labeling sections and subsections for OTC new animal drugs would
not be numbered. Headings of sections and subsections that would be
required to appear verbatim on labeling are identified in the proposed
regulations in quotations. Similarly, certain other labeling text would
be required to appear verbatim on labeling; this text is also
identified in the proposed regulations in quotations.
The proposed rule would require the labeling of approved or
conditionally approved OTC new animal drugs to comply with other
applicable requirements in proposed subpart H (see proposed Sec.
201.407).
1. Labeling Providing Full Product Information (Proposed Sec.
201.407(a))
The proposed rule uses the term ``full prescribing information'' to
identify all information necessary for the safe and effective use of
approved or conditionally approved Rx new animal drugs, and the
proposed regulations use that term for Rx new animal drugs. The concept
of a component of labeling providing all information necessary for the
safe and effective use of an approved or conditionally approved OTC new
animal drug is equally important. FDA proposes that the term used for
this information for approved or conditionally approved OTC new animal
drugs would be ``full product information'' because OTC new animal
drugs are not prescribed.
The proposed rule would establish content and format requirements
for the component of labeling that provides full product information
for approved or conditionally approved OTC new animal drugs (see
proposed Sec. 201.407(a)).
If a package insert is provided with an approved or conditionally
approved OTC new animal drug, the proposed rule would require the
package insert to include full product information (see proposed Sec.
201.407(a)). If a package insert is provided with an approved or
conditionally approved OTC new animal drug, the label would be required
to comply with proposed Sec. 201.407(b) or (c), and any secondary
container labeling would be required to comply with proposed Sec.
201.407(d).
If a package insert is not provided with an approved or
conditionally approved OTC new animal drug, but a secondary container
is provided, then the secondary container labeling would be required to
provide full product information (see proposed Sec. 201.407(a)). If
full product information is provided on the secondary container
labeling, in accordance with section 201(k) of the FD&C Act, proposed
Sec. 201.407(a) would allow the secondary container labeling to
exclude any portions of full product information that would be required
to appear on the label if such information is easily legible through
the secondary container (see proposed Sec. 201.407(a)).
If no package insert or secondary container is provided with an
approved or conditionally approved OTC new animal drug, then the label
would be required to include full product information (see proposed
Sec. 201.407(a)).
The proposed rule would require the following information to be
presented in full product information for approved or conditionally
approved OTC new animal drugs and in the following order. Unless
otherwise indicated, this information would be the same as that
required by proposed Sec. 201.405(a) for full prescribing information
for approved or conditionally approved Rx new animal drugs.
a. Drug product identification. The proposed rule would require
this section of full product information to include the proprietary
name of the finished drug product and the established name of the drug
product. If not included as part of the established name of the drug
product, the route(s) of administration and dosage form of the finished
drug product would be required to be included in this section as well
(see proposed Sec. 201.407(a)(1)(i) through (iv)).
The established name and strength or concentration of each active
ingredient would also be required. The strength or concentration of
each active ingredient would be allowed to be excluded from full
product information provided on a package insert if the package insert
applies to multiple strengths or concentrations for the same OTC new
animal drug (see proposed Sec. 201.407(a)(1)(v)).
If FDA determines that identifying the pharmacological class of an
OTC new animal drug on labeling would be helpful in facilitating its
safe and effective use, the proposed rule would require that the
pharmacological class be included in this section of full product
information (see proposed Sec. 201.407(a)(1)(vi)).
b. Conditional approval statement. For conditionally approved OTC
new animal drugs, the proposed rule would require this section of full
product information to include a conditional approval statement, as
described in proposed Sec. 201.405(a)(3) for full prescribing
information for conditionally approved Rx new animal drugs (see
proposed Sec. 201.407(a)(2)).
c. ``Uses.'' This section of full product information would be
required to have the heading ``Uses,'' followed by the approved or
conditionally approved indication(s) and target animal(s) in the
following format: ``For [indication(s)] in [target animal(s)]'' (see
proposed Sec. 201.407(a)(3)).
This section of full product information would be similar to the
``Indications for Use'' section of full prescribing information for Rx
new animal drugs, as described in proposed
[[Page 18286]]
Sec. 201.405(a)(7). For OTC new animal drugs, the heading ``Uses'' may
be better understood by the layperson and is consistent with the
requirements for labeling of OTC human drugs (see Sec. 201.66(c)(4)).
If FDA approves or conditionally approves an OTC new animal drug
for use only under specific conditions, such as in conjunction with a
specific diet, then the proposed rule would require that this
information be specified in the ``Uses'' section of full product
information (see proposed Sec. 201.407(a)(3)(ii)).
FDA may require a statement in the ``Uses'' section of full product
information describing the relative effectiveness of doses within the
approved range of doses (see proposed Sec. 201.407(a)(3)(iii)). This
requirement primarily pertains to OTC new animal drugs that affect the
structure or function of the body of an animal (section 201(g)(1)(C) of
the FD&C Act) but are not intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease (section 201(g)(1)(B)
of the FD&C Act), e.g., drugs that increase the rate of weight gain or
feed efficiency in food-producing animals. For these new animal drugs,
all doses within the range presented on the approved labeling must be
effective for their intended use(s) (see 21 CFR 514.4(b)(2)(i)). For
new animal drugs intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease, the lowest dose of the dose range
must be effective for the intended use(s). However, the doses within
the approved range do not need to be more effective than any other
doses within the same range. For OTC new animal drugs approved for
structure or function indications, if the highest approved dose(s) is
not more effective compared to the next lower approved dose(s), the
proposed rule would be able to require a statement in the ``Uses''
section to inform the user that a higher dose(s) is not more effective
than the next lower dose(s).
For safety and/or effectiveness reasons, we may require a
statement(s) in the ``Uses'' section of full product information
identifying animals for which the OTC new animal drug has not been
approved or conditionally approved (see proposed Sec.
201.407(a)(3)(iv)).
d. Extralabel use statement. The proposed rule would require this
section of full product information to include an extralabel use
statement (see proposed Sec. 201.407(a)(4)). In accordance with part
530, extralabel use of approved new animal drugs is not permitted
except by or on the order of a licensed veterinarian and under the
conditions described in that chapter. The required statement would be:
``It is a violation of Federal law to use this drug product other than
as directed in the labeling or as directed by your veterinarian.'' It
is important for the layperson to know when it is a violation of
Federal law to use drugs in animals in an extralabel manner.
e. Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use, in accordance with Sec. 530.41,
the proposed rule would require this section of full product
information to include an extralabel use prohibition statement, as
described in proposed Sec. 201.405(a)(5) for full prescribing
information for Rx new animal drugs (see proposed Sec. 201.407(a)(5)).
Few OTC new animal drugs are prohibited from extralabel use under Sec.
530.41. However, for the rare situation in which an approved OTC new
animal drug is prohibited from extralabel use under Sec. 530.41, this
statement would be included in addition to the appropriate extralabel
use statement that would be required by proposed Sec. 201.407(a)(4).
f. ``Description.'' The proposed rule would require this section of
full product information to have the heading ``Description,'' followed
by a description of the new animal drug. The description would include
the proprietary name of the finished drug product and established name
of the drug product, and the route(s) of administration and dosage form
if not included as part of the established name. The description would
also include identifying characteristics of the dosage form, such as
color, shape, coating, scoring, and imprinting. All approved and
available strengths or concentrations of the new animal drug to which
full product information applies would need to be identified in this
section of full product information. If the drug product was sterile,
this fact would also be identified in this section of full product
information (see proposed Sec. 201.407(a)(6)).
When inactive ingredients are provided on the labeling, the
proposed rule would require they be listed in the ``Description''
section in decreasing order of predominance, by weight or concentration
(see proposed Sec. 201.407(a)(6)(viii)). We encourage sponsors to list
all inactive ingredients on labeling to better inform users about the
product.
g. ``Warnings.'' The proposed rule would require this section of
full product information for all approved or conditionally approved OTC
new animal drugs, and it would have the heading ``Warnings'' (see
proposed Sec. 201.407(a)(7)). This section of full product information
would be similar to the ``Warnings and Precautions'' section proposed
for full prescribing information for Rx new animal drugs, as described
in proposed Sec. 201.405(a)(10). However, ``precautions'' would be
excluded from this section of full product information and instead be
provided in the ``Additional Recommendations'' section of full product
information, as described in proposed Sec. 201.407(a)(8). A more
complete explanation of the basis for this proposal is provided in the
discussion of the ``Animal Safety Warnings'' subsection for OTC new
animal drugs in proposed Sec. 201.407(a)(7)(iii).
i. ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods.'' All OTC new animal drugs approved or conditionally approved
for use in food-producing animals, would be required to have as the
first subsection of the ``Warnings'' section of full product
information a subsection with the heading ``Withdrawal Periods and
Residue Warnings'' or ``Withdrawal Periods.'' This subsection would
provide human food safety warnings, including milk discard times,
withdrawal periods, and residue warning statements, as applicable to
the new animal drug (see proposed Sec. 201.407(a)(7)(i)). This
subsection of full product information would be the same as described
in proposed Sec. 201.405(a)(10)(i) for full prescribing information
for Rx new animal drugs.
ii. ``User Safety Warnings.'' The proposed rule would require this
subsection of the ``Warnings'' section of full product information to
have the heading ``User Safety Warnings,'' followed by the user safety
warnings (see proposed Sec. 201.407(a)(7)(ii)). This subsection of
full product information would be the same as described in proposed
Sec. 201.405(a)(10)(ii) for full prescribing information for Rx new
animal drugs.
iii. ``Animal Safety Warnings.'' For OTC new animal drugs with
contraindications, target animal safety warnings that identify any
serious adverse reaction or potential hazard to the target animal(s)
associated with the use of the new animal drug, adverse reactions, or
post-approval adverse drug experiences, the proposed rule would require
this subsection of the ``Warnings'' section of full product information
to have the heading ``Animal Safety Warnings,'' followed by the
contraindications, target animal safety warnings, adverse reactions,
and post-approval adverse drug experiences
[[Page 18287]]
(see proposed Sec. 201.407(a)(7)(iii)). This proposed subsection of
full product information would differ in some ways from the ``Animal
Safety Warnings and Precautions'' subsection of full prescribing
information proposed for Rx new animal drugs, as described in proposed
Sec. 201.405(a)(10)(iii), and these differences are the basis for the
different proposed titles of these sections, i.e., ``Warnings'' for OTC
new animal drugs versus ``Warnings and Precautions'' for Rx new animal
drugs.
The definition of ``precautions'' in proposed Sec. 201.403 is
``any special care to be exercised for safe and effective use of the
new animal drug. This may include recommended screening, monitoring, or
diagnostic tests.'' Precautions related to Rx new animal drugs may
include screening, special care and monitoring, or diagnostic tests
intended to be performed by a veterinarian. Furthermore, precautions
related to Rx new animal drugs are often related to, and difficult to
distinguish from, target animal safety warnings. On the other hand, OTC
new animal drugs do not require professional veterinary expertise to
properly administer the drug, provide adequate post-treatment care, or
monitor effects after use of the drug. For OTC new animal drugs,
precautions provide additional recommendations to the layperson and are
distinguishable from target animal safety warnings. For example, this
may include information on when to administer the drug relative to
feeding, or a recommendation to have a sound mastitis monitoring
program before using the drug, etc. This advice is distinguishable from
warnings for OTC new animal drugs. Therefore, for better clarity to the
layperson, we propose that precautions for OTC new animal drugs not be
included in the ``Animal Safety Warnings'' section of full product
information and instead would be included in a separate section called
``Additional Recommendations,'' as described in proposed Sec.
201.407(a)(8).
In addition, the ``Animal Safety Warnings'' subsection of full
product information for OTC new animal drugs would differ from the
``Animal Safety Warnings and Precautions'' subsection of full
prescribing information for Rx new animal drugs in terms of
presentation of warning information. For OTC new animal drugs, all
potential risks of the drug to the target animal would be included:
contraindications, target animal safety warnings, adverse reactions,
and post-approval adverse drug experiences as determined by FDA. For Rx
new animal drugs, this information would be provided in different
sections of full prescribing information.
For OTC new animal drugs, including all potential risks to the
target animal in one subsection of full product information might be
clearer for the layperson and increase the likelihood that all of the
information would be read. Furthermore, identifying the risks to the
target animal on labeling as ``contraindications,'' ``target animal
safety warnings,'' ``adverse reactions,'' or ``post-approval adverse
drug experience'' may be confusing to a layperson because they may not
know the differences between the terms. The subsection heading ``Animal
Safety Warnings'' would be understood by the layperson as meaning risks
to the target animal. Therefore, the proposed rule would require that
all risks to the target animal for OTC new animal drugs be simply
identified as ``Animal Safety Warnings'' and placed in this subsection
of full product information. All risk information listed under ``Animal
Safety Warnings'' would be required to be listed in decreasing order of
severity to emphasize the most critical risks to the target animal (see
proposed Sec. 201.407(a)(7)(iii)).
iv. ``Environmental Warnings.'' For new animal drugs having
environmental warnings, the proposed rule would require this subsection
of the ``Warnings'' section of full product information to have the
heading ``Environmental Warnings,'' followed by the environmental
warnings (see proposed Sec. 201.407(a)(7)(iv)). This subsection of
full product information would be the same as described in proposed
Sec. 201.405(a)(10)(iv) for full prescribing information for Rx new
animal drugs.
v. ``Other Warnings.'' For OTC new animal drugs having warnings not
more appropriately placed in other ``Warnings'' subsections, the
proposed rule would require the last subsection of the ``Warnings''
section of full product information to have the heading ``Other
Warnings,'' followed by those warnings (see proposed Sec.
201.407(a)(7)(v)). This subsection of full product information would be
the same as described in proposed Sec. 201.405(a)(10)(v) for full
prescribing information for Rx new animal drugs.
h. ``Additional Recommendations.'' For OTC new animal drugs having
precautions, the proposed rule would require this section of full
product information to have the heading ``Additional Recommendations,''
followed by all precautions (see proposed Sec. 201.407(a)(8)). As
described in its proposed definition, precautions include any special
care to be exercised for safe and effective use of the new animal drug.
As discussed with respect to proposed Sec. 201.407(a)(7)(iii),
regarding ``Animal Safety Warnings,'' precautions are distinguishable
from target animal safety warnings for OTC new animal drugs. However,
because the term ``precautions'' as intended by these proposed
regulations may not be known or understood by the layperson, the title
``Additional Recommendations'' is proposed.
i. ``Other Effects You May Notice.'' For OTC new animal drugs that
have effects on the target animal(s) that are not considered
contraindications, target animal safety warnings, adverse reactions, or
post-approval adverse drug experiences, and FDA determines these
effects are required to be described on labeling, the proposed rule
would require this section of full product information to have the
heading ``Other Effects You May Notice,'' followed by a description of
the effects (see proposed Sec. 201.407(a)(9)). We consider this
information important for owners of animals, and this information is
currently provided on the labeling of some OTC new animal drugs.
For example, some OTC new animal drugs approved for increased rate
of weight gain and/or feed efficiency in feedlot beef cattle have
effects on the leanness or tenderness of the carcass of those animals.
Similarly, OTC new animal drugs that increase milk production in dairy
cows or the efficiency by which they produce milk may alter the fat
percent content of the milk. These effects, which are currently
described on the approved labeling for these products, are not
considered negative health effects on the target animal nor are they of
human food safety concern. However, these effects could be mistaken for
symptoms of an underlying health problem in the target animal, such as
poor nutritional status. For this reason, information of this type may
be considered material under section 201(n) of the FD&C Act such that
it would be required to be disclosed in the labeling for these products
on the basis that such disclosures may preclude unnecessary concern and
inappropriate medical treatment. Similarly, some topically applied OTC
new animal drugs for companion animals might permanently (but
harmlessly) alter the color of the fur at the application site. These
types of potential effects that are not safety concerns, but rather
provide important information to the layperson, would be included in
this section of full product information.
j. ``Directions.'' The proposed rule would require this section of
full
[[Page 18288]]
product information to have the heading ``Directions,'' followed by the
directions for use of the OTC new animal drug for each indication and
target animal (see proposed Sec. 201.407(a)(10)). The corresponding
section of full prescribing information for Rx new animal drugs would
be called ``Dosage and Administration,'' as described in proposed Sec.
201.405(a)(9). However, for OTC new animal drugs, the term
``Directions'' may be better understood by the layperson. In addition,
the term ``Directions'' is also used in labeling of OTC human drugs
(see Sec. 201.66(c)(6)).
The ``Directions'' section of full product information is
intentionally proposed for placement after the ``Warnings'' section.
This is in contrast to the ``Dosage and Administration'' section in
full prescribing information for Rx new animal drugs, which, except for
``Boxed Warnings,'' would be placed before ``Contraindications,''
``Warnings and Precautions,'' ``Adverse Reactions,'' and other
information about the effects of the drug. The intent in presenting
``Directions'' after the ``Warnings'' section in full product
information for OTC new animal drugs is to increase the likelihood that
the layperson will read the ``Warnings'' section before using the drug.
This placement approach is similar to that used in labeling of OTC
human drugs (see Sec. 201.66(c)(6)).
The ``Directions'' section of full product information would be
required to include information necessary for treatment of the animal
with the OTC new animal drug in accordance with FDA approval or
conditional approval, including route(s) of administration; specific
site(s) of administration, if applicable; dose or dose range, intervals
between doses, if applicable; and duration of treatment. For some
injectable products, FDA may require a statement of maximum volume per
injection site to facilitate the drug's safe and effective use, and the
proposed rule would require this information to be included in this
section of full product information. Other required dosage and
administration information would be included in this section of full
product information. See proposed Sec. 201.407(a)(10).
k. ``Net Contents.'' The proposed rule would require this section
of full product information, when presented on the label or the
secondary container labeling, to have the heading ``Net Contents,''
followed by the contents of the immediate container, in accordance with
Sec. 201.62 (21 CFR 201.62), or the secondary container, respectively.
The proposed rule would exclude a ``Net Contents'' section from package
inserts (see proposed Sec. 201.407(a)(11)).
l. ``How Supplied.'' The proposed rule would require this section
of full product information to have the heading ``How Supplied,''
followed by information on available strengths, concentrations, and
container sizes to which the labeling applies (see proposed Sec.
201.407(a)(12)). This section of full product information would be the
same as described in proposed Sec. 201.405(a)(19) for full prescribing
information for Rx new animal drugs.
m. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of full product information to have the heading
``Storage, Handling, and Disposal,'' followed by drug storage
information, as well as any required handling and drug disposal
information (see proposed Sec. 201.407(a)(13)). This section of full
product information would be the same as described in proposed Sec.
201.405(a)(20) for full prescribing information for Rx new animal
drugs.
n. ``Questions/Comments?'' The proposed rule would require this
section of full product information to have the heading ``Questions/
Comments?,'' followed by the sponsor's contact information for
consumers to facilitate requesting additional information or to report
suspected adverse drug experiences. FDA's contact information for
voluntary reporting of adverse drug experiences for animal drugs would
also be required (see proposed Sec. 201.407(a)(14)). The ``Questions/
Comments?'' section of full product information would be similar to the
``Contact Information'' section in proposed Sec. 201.405(a)(12) for
full prescribing information for Rx new animal drugs.
The ``Questions/Comments?'' heading might be clearer than ``Contact
Information'' to the layperson using OTC new animal drugs. Furthermore,
the heading ``Questions?'' or ``Questions or comments?'' is used for
OTC human drug labeling (see Sec. 201.66(c)(9)). Also, the phrase ``To
report side effects, contact . . .'' is proposed for full product
information for OTC new animal drugs rather than ``To report suspected
adverse drug experiences, contact . . .,'' which is the phrase proposed
for full prescribing information for Rx new animal drugs. The term
``side effects'' may be better understood by the layperson than the
term ``suspected adverse drug experiences.'' Also, the term ``side
effects'' may be used in labeling of OTC human drugs (see Sec.
201.66(c)(5)(vii) (21 CFR 201.66(c)(5)(vii)).
The sponsor's contact information would be the name of the
manufacturer, packer, or distributor, whichever is identified in the
``Name and place of business'' section of full product information (see
proposed Sec. 201.407(a)(16)). If more than one business is identified
in the ``Name and place of business'' section of full product
information, the drug sponsor would select the most appropriate of
these businesses to use in the ``Questions/Comments?'' section to
provide additional information about the OTC new animal drug and to
contact regarding suspected adverse drug experiences.
The statements in this section of full product information would be
required to be structured as follows: ``Contact [insert name of
business] at [insert business telephone number] or [insert business web
address]. To report side effects, contact [insert name of business] at
[insert business telephone number]. For additional information about
reporting side effects for animal drugs, contact FDA at [insert current
FDA telephone number for voluntary reporting of adverse drug
experiences] or [insert current FDA web address for voluntary reporting
of adverse drug experiences].'' Sponsors can search FDA's website or
contact FDA by telephone to find the current FDA telephone number or
web address for voluntary reporting of adverse drug experiences for
animal drugs.
o. NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the proposed rule would require this
section of full product information to include an ``NADA approval
statement'' or ``ANADA approval statement,'' respectively (see proposed
Sec. 201.407(a)(15)). This section of full product information would
be the same as described in proposed Sec. 201.405(a)(21) for full
prescribing information for Rx new animal drugs.
p. Name and place of business. The proposed rule would require this
section of full product information to identify the name and place of
business of the manufacturer, packer, or distributor (see proposed
Sec. 201.407(a)(16)). This section of full product information would
be the same as described in proposed Sec. 201.405(a)(22) for full
prescribing information for Rx new animal drugs.
q. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of full product information when provided on the
secondary container labeling or the label. Package inserts are excluded
from this requirement because they might apply to multiple lots of
secondary or immediate containers of the OTC new animal drug. When full
product
[[Page 18289]]
information is provided on the secondary container labeling or the
label, this section would be required to have the heading ``Lot Number
and Expiration Date,'' followed by the identifying lot or control
number of the OTC new animal drug within the secondary container or
immediate container (see proposed Sec. 201.407(a)(17)). A lot or
control number would help us more easily to identify and trace back a
specific lot of a product should a problem be reported to FDA. The
proposed rule would also require this section to include the expiration
date of the OTC new animal drug within the secondary container or
immediate container, in accordance with Sec. 201.17. An expiration
date better ensures that the new animal drug would not be used after it
expires.
Alternatively, the proposed rule would allow for this section of
full product information to refer to the location on the secondary
container labeling, secondary container, label, or immediate container
where the lot or control number and expiration date are printed (see
proposed Sec. 201.407(a)(17)). As an example, if the lot number and
expiration date are printed on the bottom flap of a secondary
container, then the secondary container labeling may state in this
section, ``See carton bottom flap for lot number and expiration date.''
However, if full product information is provided on the secondary
container labeling, in accordance with Sec. 201.17, the proposed rule
would allow an expiration date to be excluded from the secondary
container labeling or secondary container if the expiration date
provided on the label or immediate container is easily legible through
the secondary container.
r. ``Revision Date.'' The proposed rule would require this section
of full product information to have the heading ``Revision Date,''
followed by the date of the most recent revision of the component of
labeling that provides full product information, listing the month
followed by the year (see proposed Sec. 201.407(a)(18)). This
information is important to ensure that the most current approved
version of the labeling is being used.
2. OTC New Animal Drug Label Not Providing Full Product Information
(OTC Label) (Proposed Sec. 201.407(b))
The proposed rule would establish content and format requirements
for the information presented on the label for approved or
conditionally approved OTC new animal drugs (OTC label) where the label
does not provide full product information (see proposed Sec.
201.407(b)). As described previously in section V.E.1 regarding
labeling providing full product information, the label for an OTC new
animal drug would include full product information only if there is no
package insert or secondary container labeling.
Proposed Sec. 201.407(b) would apply to OTC labels that are of
adequate size to contain the proposed required information per that
paragraph, whereas proposed Sec. 201.407(c) would apply to small
labels for OTC new animal drugs that are not of adequate size to
contain all the proposed required information in proposed Sec.
201.407(b).
OTC new animal drugs labels to which Sec. 201.407(b) would apply
may consist of a single panel, a front panel and one side or back
panel, or a front panel and multiple side and/or back panels, and the
proposed rule would provide for such label designs (see proposed Sec.
201.407(b)). For OTC labels with a front panel and one side or back
panel, the proposed rule would require certain information for the
front panel (see proposed Sec. 201.407(b)(1)), and the side or back
panel (see proposed Sec. 201.407(b)(2)). For OTC labels consisting of
a single panel, the proposed rule would require the information
identified in proposed Sec. 201.407(b)(1) followed by the information
identified in proposed Sec. 201.407(b)(2), in order, on the single
panel. For OTC labels with a front panel and multiple side and/or back
panels, the information identified in proposed Sec. 201.407(b)(1)
followed by the information identified in proposed Sec. 201.407(b)(2)
would be required in order, starting on the front panel, continuing on
the panel immediately to the right of the front panel, and continuing
to fill the panels to the right until all of the information in
proposed Sec. 201.407(b)(1) and (2) was presented. In all instances,
the information in proposed Sec. 201.407(b)(2)(iii) and (iv),
concerning active ingredients and inactive ingredients, would need to
appear on the same panel.
a. Front panel. The proposed rule would require the following
information to be presented on the front panel of the OTC label for an
approved or conditionally approved OTC new animal drug and in the
following order (see proposed Sec. 201.407(b)(1)). Unless otherwise
indicated, this information would be the same as that required by
proposed Sec. 201.405(a) for full prescribing information for approved
or conditionally approved Rx new animal drugs or proposed Sec.
201.407(a) for full product information for approved or conditionally
approved OTC new animal drugs.
i. Drug product identification. The proposed rule would require
this section of the OTC label to include drug product identification
(see Sec. 201.407(b)(1)(i)). This information may help the user to
identify the product quickly and correctly and distinguish it from
other, similar products. The information included in this section of
the OTC label would include the same information as that in the drug
product identification section of full product information, as
described in proposed Sec. 201.407(a)(1), in addition to a statement
that the drug product is sterile, if applicable. Full product
information would require a drug product identification section and
``Description'' section. Full product information for sterile OTC new
animal drugs would be required to identify in the ``Description''
section that the drug is sterile. However, due to space limitations, no
``Description'' section is proposed for the OTC label. Instead, the
drug product identification section of the OTC label for sterile OTC
new animal drugs would be required to state that the drug product is
sterile. See proposed Sec. 201.407(b)(1)(i).
ii. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the OTC
label to include a conditional approval statement, as described in
proposed Sec. 201.405(a)(3)) for full prescribing information for Rx
new animal drugs (see proposed Sec. 201.407(b)(1)(ii)).
iii. ``Uses.'' The proposed rule would require this section of the
OTC label to have the heading ``Uses,'' followed by the ``Uses''
section, as described in proposed Sec. 201.407(a)(3) for full product
information. If there is insufficient space on the OTC label for the
complete ``Uses'' section as described in proposed Sec. 201.407(a)(3),
then the proposed rule would require the sponsor to include in this
section of the OTC label the statement required in proposed Sec.
201.407(a)(3)(i), i.e., ``For [indication(s)] in [target animal(s)]''.
If there is insufficient space on the OTC label for the statement in
proposed Sec. 201.407(a)(3)(i), then an abbreviated version of the
statement would be required: ``For [abbreviated indication(s)] in
[target animal(s)].'' In either situation where there is insufficient
space on the OTC label for the complete ``Uses'' section as specified
in proposed Sec. 201.407(a)(3), the required statement would be
followed by one of the following statements: ``See package insert for
complete `Uses''' if full product information is provided on a package
insert; or ``See package labeling for
[[Page 18290]]
complete `Uses''' if full product information is provided on the
secondary container labeling. See proposed Sec. 201.407(b)(1)(iii).
The complete ``Uses'' section as described in proposed Sec.
201.407(a)(3) may exceed the available space on the OTC label if, for
example, it includes specific conditions of use (proposed Sec.
201.407(a)(3)(ii)), a statement describing the relative effectiveness
of doses within the approved range of doses (proposed Sec.
201.407(a)(3)(iii)), animals for which the new animal drug is not
approved or conditionally approved (proposed Sec. 201.407(a)(3)(iv),
and/or the indication(s) is lengthy and/or complex.
iv. Extralabel use statement. The proposed rule would require this
section of the OTC label to include the extralabel use statement, as
described in proposed Sec. 201.407(a)(4) for full product information
(see proposed Sec. 201.407(b)(1)(iv)).
v. Extralabel use prohibition statement. For approved OTC new
animal drugs prohibited from extralabel use, in accordance with Sec.
530.41, the proposed rule would require this section of the OTC label
to include the extralabel use prohibition statement, as described in
proposed Sec. 201.405(a)(5) for full prescribing information for Rx
new animal drugs (see proposed Sec. 201.407(b)(1)(v)).
vi. ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods.'' For new animal drugs approved or conditionally approved for
use in food-producing animals, the proposed rule would require this
section of the OTC label to have the heading ``Withdrawal Periods and
Residue Warnings'' or ``Withdrawal Periods,'' followed by all human
food safety warnings, including milk discard times, withdrawal periods,
and residue warning statements, as described in proposed Sec.
201.405(a)(10)(i) for full prescribing information for Rx new animal
drugs. If there is insufficient space on the front panel of the OTC
labels with only a front panel and one side or back panel, the proposed
rule would require this section to be provided on the side or back
panel of the OTC label immediately following the complete product
information statement specified in proposed Sec. 201.407(b)(2)(i). See
proposed Sec. 201.407(b)(1)(vi).
vii. ``Net Contents.'' The proposed rule would require this section
of the OTC label to have the heading ``Net Contents,'' followed by the
contents of the immediate container, in accordance with Sec. 201.62
(see proposed Sec. 201.407(b)(1)(vii)).
viii. NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the proposed rule would require
this section of the OTC label to include the NADA or ANADA approval
statement, as described in proposed Sec. 201.405(a)(21) for full
prescribing information for Rx new animal drugs (see proposed Sec.
201.407(b)(1)(viii)).
b. Side or back panel. The proposed rule would require the
following information to be presented on the side or back panel of the
OTC label for an approved or conditionally approved OTC new animal drug
in the following order (see proposed Sec. 201.407(b)(2)). Unless
otherwise indicated, this information would be the same as that
required by proposed Sec. 201.405(a) for full prescribing information
for approved or conditionally approved Rx new animal drugs or proposed
Sec. 201.407(a) for full product information for approved or
conditionally approved OTC new animal drugs.
i. Complete product information statement. The proposed rule would
require this section of the OTC label to include one of two statements
(see proposed Sec. 201.407(b)(2)(i)). If full product information is
provided on the package insert, the following statement would be used:
``Before using this drug, read package insert for complete product
information.'' If full product information is provided on the secondary
container labeling, the following statement would be used: ``Before
using this drug, read package labeling for complete product
information.'' Because full product information would not be provided
on the OTC label, the purpose of the statements would be to remind the
user to read full product information before using the OTC new animal
drug.
ii. ``Directions.'' The proposed rule would require this section of
the OTC label to have the heading ``Directions,'' followed by the
``Directions'' section as described in proposed Sec. 201.407(a)(10)
for full product information. If there is insufficient space on the OTC
label for the complete requirements as specified in Sec.
201.407(a)(10), or if it is necessary for additional information
provided in full product information that is not provided on the OTC
label to be read before administering the drug (e.g., complete warnings
and/or additional recommendations), then FDA may exclude this section
from the OTC label (see proposed Sec. 201.407(b)(2)(ii)). For example,
if an OTC new animal drug is approved for multiple indications and/or
target animals, there may be different target animal safety warnings or
precautions associated with each indication and/or target animal. This
information would be provided in full product information for the OTC
new animal drug (in the ``Animal Safety Warnings'' subsection and
``Additional Recommendations'' section, respectively), but there may be
insufficient space for it on the OTC label. Excluding the
``Directions'' section from the OTC label in this situation helps to
ensure that the user would read full product information, which would
include the ``Directions'' section as well as the ``Animal Safety
Warnings'' subsection and ``Additional Recommendations'' section,
before treating the animal. The user would also be reminded to read
full product information before using the drug via the complete product
information statement that would be required in the previous section of
the OTC label by proposed Sec. 201.407(b)(2)(i).
iii. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the OTC label to have the heading
``Active Ingredient'' or ``Active Ingredients,'' followed by the
established name and strength or concentration of each active
ingredient (see proposed Sec. 201.407(b)(2)(iii)).
iv. ``Inactive Ingredients.'' When inactive ingredients are
provided on the OTC label, the proposed rule would require they be
listed in the ``Inactive Ingredients'' section in decreasing order of
predominance, by weight or concentration, as described in proposed
Sec. 201.405(a)(6)(viii) for full prescribing information for Rx new
animal drugs (see proposed Sec. 201.407(b)(2)(iv)).
v. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the OTC label to have the heading ``Storage,
Handling, and Disposal,'' followed by drug storage, handling, and
disposal information, as described in proposed Sec. 201.405(a)(20) for
full prescribing information for Rx new animal drugs (see proposed
Sec. 201.407(b)(2)(v)).
vi. Name and place of business. The proposed rule would require
this section of the OTC label to identify the name and place of
business of the manufacturer, packer, or distributor, as required in
section 502(b) of the FD&C Act (see proposed Sec. 201.407(b)(2)(vi)).
vii. ``Lot Number and Expiration Date'' or ``Lot Number''. The
proposed rule would require this section of the OTC label to have the
heading ``Lot Number and Expiration Date'' or ``Lot Number,'' followed
by the identifying lot or control number of the OTC new animal drug
within the immediate container (see proposed Sec. 201.407(b)(2)(vii)).
A lot or control number would allow us more easily to identify and
trace back a specific lot of a product should a problem be reported
[[Page 18291]]
to FDA. We would also require this section of the OTC label to include
the expiration date of the OTC new animal drug within the immediate
container, in accordance with Sec. 201.17. An expiration date on the
OTC label better ensures that the new animal drug would not be used
after it expires. Alternatively, the proposed rule would allow for this
section to refer to the location on the OTC label or immediate
container where the lot or control number and expiration date are
printed (see proposed Sec. 201.407(b)(2)(vii)). As an example, if the
lot number and expiration date are printed at the top of the immediate
container, then the OTC label may state in this section, ``See top of
container for lot number and expiration date.'' If the immediate
container provides a single dose of the OTC new animal drug and is
packaged individually in a secondary container that provides an
expiration date on the secondary container labeling or secondary
container, the proposed rule would not require an expiration date on
the OTC label or immediate container, in accordance with Sec. 201.17.
Under such provision, this section of the OTC label would be required
to be entitled ``Lot Number.''
viii. ``Revision Date.'' The proposed rule would require the last
section of the OTC label to have the heading ``Revision Date,''
followed by the date of the most recent revision of the OTC label,
listing the month followed by the year (see proposed Sec.
201.407(b)(2)(viii)).
3. OTC New Animal Drug Small Label (OTC Small Label) (Proposed Sec.
201.407(c))
The proposed rule would establish content and format requirements
for the small label for OTC new animal drugs (OTC small label) where
the label does not provide full product information (see proposed Sec.
201.407(c)).
Some immediate containers, such as blister packs, pre-filled
syringes, and small vials, are so small that only a minimal amount of
information can be included on their label. The proposed rule would
establish requirements for OTC small labels for approved or
conditionally approved OTC new animal drugs (see proposed Sec.
201.407(c)). We recognize that the size of the label is dependent upon
the size of the immediate container. If an immediate container lacks
sufficient space to contain a label that accommodates all of the
information required by proposed Sec. 201.407(a) or (b), the
requirements of proposed Sec. 201.407(c) would instead apply. We would
ordinarily make this determination during the review of the new animal
drug and its labeling, taking into consideration the readability and
legibility of the information.
The proposed rule would require the following information to be
presented on the OTC small label for an approved or conditionally
approved OTC new animal drug and in the following order (see proposed
Sec. 201.407(c)).
a. Proprietary name of the finished drug product. The proposed rule
would require this section of the OTC small label to include the
proprietary name of the finished drug product (see proposed Sec.
201.407(c)(1)). This requirement already exists for small labels for
drugs in general in Sec. 201.10(i)(1), but is repeated in these
proposed regulations to include all requirements for labeling of
approved or conditionally approved new animal drugs in proposed subpart
H.
b. Established name of the drug product. The proposed rule would
require this section of the OTC small label to include the established
name of the drug product (see proposed Sec. 201.407(c)(2)). This
requirement already exists for small labels for drugs in general in
Sec. 201.10(i)(1), but is repeated in these proposed regulations to
include all requirements for labeling of approved or conditionally
approved new animal drugs in proposed subpart H.
c. Active ingredient(s). The proposed rule would require this
section of the OTC small label to include the established name and
strength or concentration of each active ingredient (see proposed Sec.
201.407(c)(3)). This information should reduce the risk of
miscalculating doses.
d. ``For [target animal(s)] only.'' The proposed rule would require
this section of the OTC small label to include a brief listing of the
approved target animal(s) as follows: ``For [target animal(s)] only''
(see proposed Sec. 201.407(c)(4)). The brief listing of the approved
target animal(s) is used in place of full ``Uses'' information because
OTC small labels lack sufficient space. This listing would not require
as much space on the OTC small label.
e. Complete product information statement. The proposed rule would
require this section of the OTC small label to include one of two
statements. If full product information is provided on the package
insert, the following statement would be used: ``Read package insert
for complete product information''. If full product information is
provided on the secondary container labeling, the following statement
would be used: ``Read package labeling for complete product
information.'' See proposed Sec. 201.407(c)(5). Because full product
information would not be provided on the OTC small label, the purpose
of the statements would be to remind the user to read full product
information before using the OTC new animal drug.
f. ``Net Contents.'' The proposed rule would require this section
of the OTC small label to have the heading ``Net Contents,'' followed
by the contents of the immediate container, in accordance with Sec.
201.62 (see proposed Sec. 201.407(c)(6)).
g. Name and place of business. The proposed rule would require this
section of the OTC small label to identify the name and place of
business of the manufacturer, packer, or distributor, as required in
section 502(b) of the FD&C Act (see proposed Sec. 201.407(c)(7)).
h. ``Lot, Exp. and Storage'' or ``Lot and Storage.'' The proposed
rule would require this section of the OTC small label to have the
heading ``Lot, Exp. and Storage'' or ``Lot and Storage,'' followed by
the identifying lot or control number of the OTC new animal drug within
the immediate container. A lot or control number would allow FDA more
easily to identify and trace back a specific lot of a product should a
problem be reported to FDA. The proposed rule would also require this
section of the OTC small label to include the expiration date of the
OTC new animal drug within the immediate container, in accordance with
Sec. 201.17. An expiration date on the OTC small label better ensures
that the new animal drug would not be used after it expires.
The proposed rule would also require this section of the OTC small
label to include and drug storage information for the new animal drug
(see proposed Sec. 201.407(c)(8)). Storage information is necessary to
maintain potency of the drug before its expiration date. Requiring this
information on the OTC small label is needed for safe and effective use
of new animal drugs. If the immediate container provides a single dose
of the OTC new animal drug and is packaged individually in a secondary
container that provides an expiration date on the secondary container
labeling or secondary container, the proposed rule would not require an
expiration date on the immediate container or OTC small label, in
accordance with Sec. 201.17, in which case this section of the OTC
small label would be required to be entitled ``Lot and Storage.''
i. ``Revision Date.'' The proposed rule would require this section
of the OTC small label to have the heading ``Revision Date,'' followed
by the date of the most recent revision of the OTC small label, listing
the month followed
[[Page 18292]]
by the year (see proposed Sec. 201.407(c)(9)).
4. Labeling for Secondary Containers for OTC New Animal Drugs That
Include a Package Insert (OTC Secondary Container Labeling) (Proposed
Sec. 201.407(d))
The proposed rule would establish content and format requirements
for the information on the labeling for secondary containers of
approved or conditionally approved OTC new animal drugs that include a
package insert (OTC secondary container labeling) (see proposed Sec.
201.407(d)). In this situation, the package insert would be required by
the proposed regulations to include full product information as in
proposed Sec. 201.407(a)).
In accordance with section 201(k) of the FD&C Act, the OTC
secondary container labeling could exclude any information described in
proposed Sec. 201.407(d) that would be required to appear on the OTC
label or OTC small label (see proposed Sec. 201.407(b) or (c),
respectively) if such information on the OTC label or OTC small label
was easily legible through the secondary container.
The OTC secondary container labeling to which proposed Sec.
201.407(d) would apply may consist of a front panel and one side or
back panel, or a front panel and multiple side and/or back panels.
Proposed Sec. 201.407(d) would provide for such OTC secondary
container labeling designs. For OTC secondary container labeling with a
front panel and one side or back panel, proposed Sec. 201.407(d)(1)
would provide required information for the front panel, and proposed
Sec. 201.407(d)(2) would provide required information for the side or
back panel. For OTC secondary container labeling with a front panel and
multiple side and/or back panels, the information identified in
proposed Sec. 201.407(d)(1) followed by the information identified in
proposed Sec. 201.407(d)(2) would be required in order, starting on
the front panel, continuing on the panel immediately to the right of
the front panel, and continuing to fill the panels to the right until
all of the information in proposed Sec. 201.407(d)(1) and (2) was
presented. In all instances, the information proposed in Sec.
201.407(d)(2)(iv) and (v), concerning active ingredients and inactive
ingredients, would need to appear on the same panel.
a. Front panel. The proposed rule would require the following
information to be presented on the front panel of the OTC secondary
container labeling and in the following order (see proposed Sec.
201.407(d)(1)). Unless otherwise indicated, this information would be
the same as that required by proposed Sec. 201.405(a) for full
prescribing information for approved or conditionally approved Rx new
animal drugs or proposed Sec. 201.407(a) for full product information
for approved or conditionally approved OTC new animal drugs.
i. Drug product identification. The proposed rule would require
this section of the OTC secondary container labeling to include drug
product identification (see proposed Sec. 201.407(d)(1)(i)). The
information would be the same as that included in the drug product
identification section for full product information, as described in
proposed Sec. 201.407(a)(1), and would also identify if the drug
product is sterile. Full product information would require a drug
product identification section and a ``Description'' section. Full
product information for sterile OTC new animal drugs would be required
to identify in the ``Description'' section that the drug is sterile.
However, due to space limitations, no ``Description'' section would be
required on the OTC secondary container labeling. Instead, the drug
product identification section of the OTC secondary container labeling
for sterile OTC new animal drugs would be required to state that the
drug is sterile.
ii. Conditional approval statement. For conditionally approved OTC
new animal drugs, the proposed rule would require this section of the
OTC secondary container labeling to include a conditional approval
statement, as described in proposed Sec. 201.405(a)(3) for full
prescribing information for Rx new animal drugs (see proposed Sec.
201.407(d)(1)(ii)).
iii. ``Uses.'' The proposed rule would require this section of the
OTC secondary container labeling to have the heading ``Uses,'' followed
by the ``Uses'' section, as described in proposed Sec. 201.407(a)(3)
for full product information (see proposed Sec. 201.407(d)(1)(iii)).
iv. Extralabel use statement. The proposed rule would require this
section of the OTC secondary container labeling to include the
extralabel use statement as described in proposed Sec. 201.407(a)(4)
for full product information (see proposed Sec. 201.407(d)(1)(iv)).
v. Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use, in accordance with Sec. 530.41,
the proposed rule would require this section of the OTC secondary
container labeling to include the extralabel use prohibition statement,
as described in proposed Sec. 201.405(a)(5) for full prescribing
information for Rx new animal drugs (see proposed Sec.
201.407(d)(1)(v)).
vi. ``Net Contents.'' The proposed rule would require this section
of the OTC secondary container labeling to have the heading ``Net
Contents,'' followed by the contents of the secondary container (see
proposed Sec. 201.407(d)(1)(vi)).
vii. NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the proposed rule would require
this section of the OTC secondary container labeling to include the
NADA or ANADA approval statement, as described in proposed Sec.
201.405(a)(21) for full prescribing information for Rx new animal drugs
(see proposed Sec. 201.407(d)(1)(vii)).
b. Side or back panel. The proposed rule would require the
following information to be presented on the side or back panel of the
OTC secondary container labeling and in the following order (see
proposed Sec. 201.407(d)(2)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs or proposed Sec. 201.407(a)
for full product information for approved or conditionally OTC new
animal drugs.
i. Complete product information statement. The proposed rule would
require this section of the OTC secondary container labeling to include
the statement, ``Before using this drug, read package insert for
complete product information'' (see proposed Sec. 201.407(d)(2)(i)).
Because full product information would not be provided on the OTC
secondary container labeling, the purpose of the Complete product
information statement would be to remind the user to read full product
information before using the OTC new animal drug.
ii. ``Directions.'' The proposed rule would require this section of
the OTC secondary container labeling to have the heading
``Directions,'' followed by the ``Directions'' section, as described in
proposed Sec. 201.407(a)(10) for full product information (see
proposed Sec. 201.407(d)(2)(ii)).
iii. ``Warnings.'' The proposed rule would require this section of
the OTC secondary container labeling to have the heading ``Warnings,''
followed by the ``Warnings'' section, as described in proposed Sec.
201.407(a)(7) for full product information (see proposed Sec.
201.407(d)(2)(iii)).
iv. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the OTC
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secondary container labeling to have the heading ``Active Ingredient''
or ``Active Ingredients,'' followed by the established name and
strength or concentration of each active ingredient, as described in
proposed Sec. 201.407(b)(2)(iii) for the OTC label (see proposed Sec.
201.407(d)(2)(iv)).
v. ``Inactive Ingredients.'' When inactive ingredients are provided
on the OTC secondary container labeling, the proposed rule would
require they be listed in the ``Inactive Ingredients'' section by their
established name in decreasing order of predominance, by weight or
concentration, as described in proposed Sec. 201.405(a)(6)(viii) (see
proposed Sec. 201.407(d)(2)(v)).
vi. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the OTC secondary container labeling to have
the heading ``Storage, Handling, and Disposal,'' followed by drug
storage, handling, and disposal information, as described in proposed
Sec. 201.405(a)(20) for full prescribing information for Rx animal
drugs (see proposed Sec. 201.407(d)(2)(vi)).
vii. Name and place of business. The proposed rule would require
this section of the OTC secondary container labeling to identify the
manufacturer, packer, or distributor, as described in proposed Sec.
201.405(a)(22) for full prescribing information for Rx animal drugs
(see proposed Sec. 201.407(d)(2)(vii)).
viii. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the OTC secondary container labeling to have
the heading ``Lot Number and Expiration Date,'' followed by the
identifying lot or control number of the OTC new animal drug within the
secondary container. The proposed rule would also require this section
of the OTC secondary container labeling to include the expiration date
of the OTC new animal drug within the secondary container, in
accordance with Sec. 201.17. Alternatively, the proposed rule would
allow for this section to refer to the location on the OTC secondary
container labeling or secondary container where the lot or control
number and expiration date are printed (see proposed Sec.
201.407(d)(2)(viii)). As an example, if the lot number and expiration
date are printed on the bottom flap of a secondary container, then the
labeling may state in this section, ``See carton bottom flap for lot
number and expiration date.'' However, in accordance with Sec. 201.17,
the proposed rule would allow an expiration date to be excluded from
the OTC secondary container labeling or secondary container if the
expiration date provided on the OTC label, OTC small label, or
immediate container is easily legible through the secondary container.
ix. ``Revision Date.'' The proposed rule would require this section
of the OTC secondary container labeling to have the heading ``Revision
Date,'' followed by the date of the most recent revision of the OTC
secondary container labeling, listing the month followed by the year
(see proposed Sec. 201.407(d)(2)(ix)).
5. Shipping Labeling for OTC New Animal Drugs (OTC Shipping Labeling)
(Proposed Sec. 201.407(e)
The proposed rule would establish content and format requirements
for the information on the shipping labeling for approved or
conditionally approved OTC new animal drugs (OTC shipping labeling). As
defined in proposed Sec. 201.403, shipping labeling is associated with
the outermost carton containing immediate containers, secondary
containers, and/or multiple unit (multi-unit) cartons of a new animal
drug and intended for shipment, but not display, of the product. The
proposed rule would require the OTC shipping labeling to include, among
additional information, drug product identity, the manufacturer,
packer, or distributor, and drug storage and handling conditions. See
proposed Sec. 201.407(e).
The proposed rule would require the following information to be
presented on the OTC shipping labeling and in the following order (see
proposed Sec. 201.407(e)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs or proposed Sec. 201.407(a)
for full product information for approved or conditionally approved OTC
new animal drugs.
a. Proprietary name of the finished drug product. The proposed rule
would require this section of the OTC shipping labeling to include the
proprietary name of the finished drug product (see proposed Sec.
201.407(e)(1)).
b. Established name of the drug product. The proposed rule would
require this section of the OTC shipping labeling to include the
established name of the drug product (see proposed Sec.
201.407(e)(2)).
c. Established name and strength or concentration of each active
ingredient. The proposed rule would require this section of the OTC
shipping labeling provide the established name and strength or
concentration of each active ingredient (see proposed Sec.
201.407(e)(3)).
d. Conditional approval statement. For conditionally approved OTC
new animal drugs, the proposed rule would require this section of the
OTC shipping labeling to include a conditional approval statement, as
described in proposed Sec. 201.405(a)(3) for full prescribing
information for Rx new animal drugs (see proposed Sec. 201.407(e)(4)).
e. ``Net Contents.'' The proposed rule would require this section
of the OTC shipping labeling to have the heading ``Net Contents,''
followed by the contents of the shipping carton (see proposed Sec.
201.407(e)(5)).
f. ``Storage and Handling.'' The proposed rule would require this
section of the OTC shipping labeling to have the heading ``Storage and
Handling,'' followed by drug storage information (see proposed Sec.
201.407(e)(6)). Also, any handling information required for safe and
effective use of the new animal drug would be included in this section.
Information on disposal of the new animal drug would not be required to
be included on the OTC shipping labeling.
g. NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the proposed rule would require this
section of the OTC shipping labeling to include the NADA or ANADA
approval statement, as described in proposed Sec. 201.405(a)(21) for
full prescribing information for Rx new animal drugs (see proposed
Sec. 201.407(e)(7)).
h. Name and place of business. The proposed rule would require this
section of the OTC shipping labeling to identify the name and place of
business of the manufacturer, packer, or distributor, as described in
proposed Sec. 201.405(a)(22) for full prescribing information for Rx
new animal drugs (see proposed Sec. 201.407(e)(8)).
i. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the OTC shipping labeling to have the heading
``Lot Number and Expiration Date,'' followed by the identifying lot or
control number(s) and the expiration date(s) of the OTC new animal drug
within the shipping carton (see proposed Sec. 201.407(e)(9)). The
shipping carton may contain more than one lot of the OTC new animal
drug, and therefore, more than one lot or control number and expiration
date may be listed in this section of the OTC shipping labeling.
j. ``Revision Date.'' The proposed rule would require the last
section of the OTC shipping labeling to have the heading ``Revision
Date,'' followed by
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the date of the most recent revision of the OTC shipping labeling,
listing the month followed by the year (see proposed Sec.
201.407(e)(10)).
6. Other Approved Labeling for OTC New Animal Drugs (OTC Other Approved
Labeling) (Proposed Sec. 201.407(f))
The proposed rule would establish content and format requirements
for the information presented on other approved labeling for approved
or conditionally approved OTC new animal drugs (OTC other approved
labeling) (see proposed Sec. 201.407(f)). OTC other approved labeling
includes, but is not limited to, labeling on display cartons and multi-
unit cartons (excluding shipping cartons), containing the immediate
containers or the secondary containers of the OTC new animal drug.
The proposed rule would require the following information to be
presented on the OTC other approved labeling and in the following order
(see proposed Sec. 201.407(f)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs or proposed Sec. 201.407(a)
for full product information for approved or conditionally approved OTC
new animal drugs.
a. Proprietary name of the finished drug product. The proposed rule
would require this section of the OTC other approved labeling to
include the proprietary name of the finished drug product (see proposed
Sec. 201.407(f)(1)).
b. Established name of the drug product. The proposed rule would
require this section of the OTC other approved labeling to include the
established name of the drug product (see proposed Sec.
201.407(f)(2)).
c. Established name and strength or concentration of each active
ingredient. The proposed rule would require this section of the OTC
other approved labeling to provide the established name and strength or
concentration of each active ingredient (see proposed Sec.
201.407(f)(3)).
d. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the OTC
other approved labeling to include a conditional approval statement, as
described in proposed Sec. 201.405(a)(3) for full prescribing
information for Rx animal drugs (see proposed Sec. 201.407(f)(4)).
e. Extralabel use statement. The proposed rule would require this
section of the OTC other approved labeling to include the extralabel
use statement as described in proposed Sec. 201.407(a)(4) for full
product information (see proposed Sec. 201.407(f)(5)).
f. Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use, in accordance with Sec. 530.41,
the proposed rule would require this section of the OTC other approved
labeling to include the extralabel use prohibition statement, as
described in proposed Sec. 201.405(a)(5) for full prescribing
information for Rx new animal drugs (see proposed Sec. 201.407(f)(6)).
g. ``Net Contents.'' The proposed rule would require this section
of the OTC other approved labeling to have the heading ``Net
Contents,'' followed by the contents of the container to which the OTC
other approved labeling applies (see proposed Sec. 201.407(f)(7)).
h. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the OTC other approved labeling to have the
heading ``Storage, Handling, and Disposal,'' followed by drug storage,
handling, and disposal information, as described in proposed Sec.
201.405(a)(20) for full prescribing information for Rx new animal drugs
(see proposed Sec. 201.407(f)(8)).
i. NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the proposed rule would require this
section of the OTC other approved labeling to include the NADA or ANADA
approval statement, as described in proposed Sec. 201.405(a)(21) for
full prescribing information for Rx new animal drugs (see proposed
Sec. 201.407(f)(9)).
j. Name and place of business. The proposed rule would require this
section of the OTC other approved labeling to identify the name and
place of business of the manufacturer, packer, or distributor, as
described in proposed Sec. 201.405(a)(22) for full prescribing
information for Rx new animal drugs (see proposed Sec.
201.407(f)(10)).
k. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the OTC other approved labeling to have the
heading ``Lot Number and Expiration Date,'' followed by the identifying
lot or control number of the OTC new animal drug within the container
to which the OTC other approved labeling applies. This section of the
OTC other approved labeling would also be required to include the
expiration date of the OTC new animal drug within the container to
which the OTC other approved labeling applies, in accordance with Sec.
201.17. In accordance with Sec. 201.17, the proposed rule would allow
an expiration date to be excluded from the OTC other approved labeling
if the expiration date provided on containers within or their labeling
is easily legible through the container to which the OTC other approved
labeling applies (see proposed Sec. 201.407(f)(11)).
l. ``Revision Date.'' The proposed rule would require the last
section of the OTC other approved labeling to have the heading
``Revision Date,'' followed by the date of the most recent revision of
the OTC other approved labeling, listing the month followed by the year
(see proposed Sec. 201.405(f)(12)).
F. Content and Format of Labeling for New Animal Drugs for Use in
Animal Feeds--Overview (Proposed Sec. 201.409)
The proposed rule provides content and format requirements for all
components of labeling for approved or conditionally approved new
animal drugs for use in animal feeds and that are subject to part 558,
including VFD drugs. New animal drugs for use in animal feeds are
approved in accordance with section 512 of the FD&C Act or
conditionally approved in accordance with section 571 of the FD&C Act
(see proposed Sec. 201.409). Most combination new animal drugs are
currently approved for use in animal feeds or drinking water in
accordance with section 512(d)(4) of the FD&C Act. The majority of new
animal drugs approved or conditionally approved for use in animal feeds
are intended for use in food-producing animals and to be fed to
multiple animals at one time.
As described above, proposed Sec. 201.405 (``Content and format
for prescription (Rx) new animal drug labeling'') would not apply to
approved or conditionally approved new animal drugs intended for use in
or on animal feeds under the professional supervision of a licensed
veterinarian because, in accordance with section 504(a) of the FD&C
Act, such drugs are approved or conditionally approved as VFD drugs.
The proposed rule would establish the content and format requirements
for all components of labeling for approved or conditionally approved
new animal drugs intended for use in animal feeds that are subject to
part 558, including VFD drugs (see proposed Sec. 201.409).
The proposed rule would require that labeling sections or
subsections that do not apply be omitted from the labeling for approved
or conditionally approved new animal drugs for use in animal feeds (see
proposed Sec. 201.409). For example, new animal drugs approved or
conditionally approved for use in animal feeds that are not VFD drugs
would not require a VFD cautionary statement section.
[[Page 18295]]
FDA determines the final content of each applicable section of
labeling during the review of each new animal drug as part of the
approval process.
Sponsors of new animal drugs for use in animal feeds often submit
an application for approval or conditional approval of a ``Type A
medicated article,'' which is a concentrated form of the drug intended
solely for use in the manufacture of another Type A medicated article
or medicated feeds (i.e., ``Type B medicated feeds'' and/or ``Type C
medicated feeds,'' see below), The Type A medicated article consists of
a new animal drug(s), with or without a carrier, with or without
inactive ingredients (see Sec. 558.3(b)(2) (21 CFR 558.3(b)(2))).
Type B medicated feed is intended solely for the manufacture of
other medicated feeds (Type B or Type C). It serves as an intermediate
medicated feed not approved for feeding to the target animals. It is
manufactured by diluting a Type A medicated article or another Type B
medicated feed with non-medicated feed, and at least 25 percent of its
weight is from nutritional ingredients (see Sec. 558.3(b)(3)). The
maximum approvable concentrations of new animal drugs in Type B
medicated feeds must be established in accordance with Sec.
558.3(b)(3). The specific maximum concentrations for approved new
animal drugs in Type B medicated feeds are listed in Sec. 558.4(d).
Type C medicated feed is fed directly to target animals. It may
also be used in the manufacture of another Type C medicated feed. When
fed directly to target animals, it is intended to be the animals'
complete feed or part of their total diet. It is manufactured by
diluting a Type A medicated article, a Type B medicated feed, or
another Type C medicated feed with non-medicated feed, and it contains
a substantial quantity of nutritional ingredients (see Sec.
558.3(b)(4)).
Labeling for new animal drugs intended for use in feed must be
included in the new animal drug application (see Sec. 514.1(b)(3)(v)).
Such labeling may include a Type A medicated article label,
representative labeling for Type B and Type C medicated feeds
containing the new animal drug, proprietary labeling for Type B or Type
C medicated feeds, and/or other approved labeling associated with the
Type A medicated article.
Proposed Sec. 201.409(a) identifies the information that would be
required to be included on Type A medicated article labels. A Type A
medicated article label is on the immediate container, which is
typically a bag. The Type A medicated article label provides all
information necessary for the safe and effective use of the new animal
drug.
Similar to the labeling of other approved or conditionally approved
new animal drugs, the Type A medicated article label includes product
and manufacturer, packer or distributor identification, approved or
conditionally approved indications for use, warnings, and directions
for use. In addition, the directions for use for a Type A medicated
article must include mixing directions for the manufacture of medicated
feeds from the Type A medicated article, as well as feeding directions
for the finished Type C medicated feeds manufactured from the Type A
medicated article (see Sec. 514.1(b)(3)(v)(a)).
Proposed Sec. 201.409(b) and (c) identify the information that
would be required to be included on representative Type B medicated
feed labeling and representative Type C medicated feed labeling,
respectively. Sponsors of a Type A medicated article must include in
their application representative labeling proposed for use in
manufacturing Type B and Type C medicated feeds containing the new
animal drug (see Sec. 514.1(b)(3)(v)(b)). FDA approves or
conditionally approves the use of the Type A medicated article to
manufacture Type B and Type C medicated feeds and also approves or
conditionally approves the Type A medicated article label and the
representative labeling for the Type B and Type C medicated feeds.
Representative Type B and Type C medicated feed labeling is
template labeling approved by FDA as part of an NADA or CNADA for a
Type A medicated article. Representative Type B and Type C medicated
feed labeling approved in the NADA or CNADA provide feed mills the
minimal information that must be included on the final printed labels
prepared for the respective Type B and Type C medicated feeds
manufactured containing the Type A medicated article to provide for
safe and effective use of the new animal drug for its approved or
conditionally approved indication(s) for use. FDA also uses the term
``Blue Bird labels'' to refer to representative Type B and Type C
medicated feed labeling (see 64 FR 63195 at 63197, November 19, 1999).
Because the approved or conditionally approved Type C medicated
feeds will be used as part of the diet, or as the complete diet, of the
target animals, the representative Type B and Type C medicated labeling
also provide for the nutritional requirements or content to be
specified in the final printed labels for the medicated feed.
If a final printed label for a Type B or Type C medicated feed
fails to conform to the approved representative Type B or Type C
medicated feed labeling, the medicated feed will be deemed unsafe, in
accordance with section 512(a)(2) of the FD&C Act, and adulterated, in
accordance with section 501(a)(6) of the FD&C Act.
If Type A medicated article(s) are approved or conditionally
approved for more than one indication and/or target animal, the
concentration of the new animal drug(s) may differ in the medicated
feed approved or conditionally approved for these indication(s) and/or
target animal(s). Also, the nutritional requirements or content
specified in the representative labeling for the medicated feeds may
vary for different target animals. These applications for Type A
medicated articles may include representative Type B medicated feed
labeling and representative Type C medicated feed labeling for each of
the approved uses.
Some Type A medicated articles are approved or conditionally
approved to be manufactured only directly into Type C medicated feeds.
In addition to the Type A medicated article label, the applications for
these Type A medicated articles must provide representative labeling
only for Type C medicated feeds.
If new animal drugs for use in animal feeds or drinking water are
approved for combination use, in accordance with section 512(d)(4) of
the FD&C Act, these ``combination new animal drugs'' generally provide
for more than one approved Type A medicated article to be mixed into
medicated feed or drinking water for the approved target animal. The
only labeling approved for such combination new animal drugs is
representative labeling for the medicated feeds that combines
information from the representative labeling of each individual Type A
medicated article. Combination new animal drugs exclude conditionally
approved drugs subject to section 571 of the FD&C Act. Section
512(d)(4) of the FD&C Act was amended as part of the MUMS Act of 2004
to clarify that only products approved under section 512(b)(1) of the
FD&C Act can be used in new animal drug combinations.
Proposed Sec. 201.409(f) identifies the information that would be
required to be included on other approved labeling for Type A medicated
articles. Other approved labeling for Type A medicated articles may
include shipping labeling associated with shipment of bags of the Type
A medicated article.
[[Page 18296]]
Proposed Sec. 201.409(d) identifies the information that would be
required to be included on proprietary Type B medicated feed labels. In
addition to approving or conditionally approving applications for Type
A medicated articles, FDA may also approve or conditionally approve
applications for proprietary final formulations of Type B medicated
feeds. A proprietary Type B medicated feed is intended solely for the
manufacture of Type C medicated feeds or other Type B medicated feeds
and is not approved or conditionally approved for feeding to the target
animals. For some proprietary Type B medicated feeds, the formulation
and labeling are approved in an NADA or CNADA. In other situations, the
underlying data and labeling for the proprietary Type B medicated feed
to support the approved uses are maintained in a VMF. For example, this
would include situations in which a proprietary Type B medicated feed
is manufactured via modification to an approved formulation published
in the CFR or where a feed manufacturer creates its own proprietary
formulation. The application for a proprietary Type B medicated feed
will include the proprietary label for the final Type B medicated feed
and representative Type C medicated feed labeling that directs the
preparation of final printed labels for Type C medicated feeds
manufactured from the proprietary Type B medicated feed. Applications
for proprietary final formulations of Type B medicated feeds will not
include a Type A medicated article label.
Proposed Sec. 201.409(e) identifies the information that would be
required to be included on proprietary Type C medicated feed labels.
FDA may also approve or conditionally approve applications for
proprietary final formulations of Type C medicated feeds. For some
proprietary Type C medicated feeds, the formulation and labeling are
approved in an NADA or CNADA. In other situations, the underlying data
and labeling for the proprietary Type C medicated feed to support the
approved uses are maintained in a VMF. For example, this would include
situations in which a proprietary Type C medicated feed is manufactured
via modification to an approved formulation published in the CFR or
where a feed manufacturer creates its own proprietary formulation. The
application for a proprietary Type C medicated feed will include the
proprietary label for the final Type C medicated feed.
Prior to the enactment of the ADAA, new animal drugs for use in
animal feeds were approved almost exclusively for OTC use. The ADAA
allowed for approval or conditional approval of a new type of new
animal drugs for use in or on animal feeds called the ``veterinary feed
directive drug'' (VFD drug). Although not identical, the use of VFD
drugs shares similar requirements to the use of Rx new animal drugs.
A veterinarian may only issue a VFD for use in animals under his or
her supervision or oversight in the course of his or her professional
practice, and in compliance with all applicable veterinary licensing
and practice requirements (see Sec. 558.6(b) (21 CFR 558.6(b))).
Information that must be included in a VFD is in Sec. 558.6(b).
In accordance with Sec. 558.6(a)(6), the following cautionary
statement must appear on all labeling and advertising associated with a
VFD drug: ``Caution: Federal law restricts medicated feed containing
this veterinary feed directive (VFD) drug to use by or on the order of
a licensed veterinarian.''
Some sections of proposed Sec. 201.409 are patterned after
sections of proposed Sec. 201.405 for labeling of Rx new animal drugs
or proposed Sec. 201.407 for labeling of OTC new animal drugs. These
sections include the conditional approval statement or NADA/ANADA
approval statement, indications for use, warnings, and other
information associated with the effects of the new animal drug. Other
sections of proposed Sec. 201.409 are uniquely associated with
medicated articles and feeds, such as mixing directions, feeding
directions, and information on nutritional content.
The labeling sections and subsections for new animal drugs for use
in animal feeds would not be numbered. Headings of sections and
subsections that would be required to appear verbatim on labeling are
identified in the proposed regulations in quotations. Similarly,
certain other labeling text would be required to appear verbatim on
labeling; this text is also identified in the proposed regulations in
quotations.
The proposed rule would require the labeling of approved or
conditionally approved new animal drugs for use in animal feeds and
that are subject to part 558 of this chapter to comply with other
applicable requirements in proposed subpart H (see proposed Sec.
201.409).
1. Type A Medicated Article Label (Proposed Sec. 201.409(a))
The proposed rule would establish content and format requirements
for the Type A medicated article label for new animal drugs approved or
conditionally approved for use in animal feeds (see proposed Sec.
201.409(a)). A Type A medicated article is a concentrated form of the
new animal drug intended solely for use in the manufacture of another
Type A medicated article or Type B medicated feeds and/or Type C
medicated feeds. As defined in Sec. 558.3(b)(2), a Type A medicated
article consists of a new animal drug(s), with or without a carrier,
with or without inactive ingredients. A Type A medicated article label
is on the immediate container, which is typically a bag.
The Type A medicated article label provides all information
necessary for the safe and effective use of the new animal drug.
The proposed rule would require the following information to be
presented on the Type A medicated article label for an approved or
conditionally approved new animal drug and in the following order (see
proposed Sec. 201.409(a)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs or proposed Sec. 201.407(a)
for full product information for approved or conditionally approved OTC
new animal drugs.
a. Type A medicated article identification. The proposed rule would
require this section of the Type A medicated article label to include
the proprietary name, the established name of the Type A medicated
article, and the phrase ``Type A medicated article'' or ``Type A liquid
medicated article,'' as applicable, if not included as part of the
established name of the Type A medicated article (see proposed Sec.
201.409(a)(1)).
b. VFD cautionary statement. For VFD new animal drugs, the proposed
rule would require this section of the Type A medicated article label
to include the following cautionary statement, in accordance with Sec.
558.6(a)(6): ``Caution: Federal law restricts medicated feed containing
this veterinary feed directive (VFD) drug to use by or on the order of
a licensed veterinarian.'' This statement would be required to be
displayed prominently and conspicuously on the Type A medicated article
label (see proposed Sec. 201.409(a)(2)).
c. ``For further manufacturing only.'' The proposed rule would
require this section of the Type A medicated label to include the
statement, ``For further manufacturing only'' (see proposed Sec.
201.409(a)(3)). This statement would indicate that the Type A medicated
article can only be used to manufacture another Type A medicated
article or a medicated feed. A Type A medicated article cannot be fed
directly to animals.
[[Page 18297]]
d. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the Type
A medicated article label to include a conditional approval statement,
as described in proposed Sec. 201.405(a)(3) for full prescribing
information for conditionally approved Rx new animal drugs (see
proposed Sec. 201.409(a)(4)).
e. ``Indications for Use.'' The proposed rule would require this
section of the Type A medicated article label to have the heading
``Indications for Use,'' followed by the approved or conditionally
approved indication(s) and target animal(s), as described in proposed
Sec. 201.407(a)(3) for full product information for OTC new animal
drugs, with the exception of the heading of the section (see proposed
Sec. 201.409(a)(5)).
f. Extralabel use statement. The proposed rule would require this
section of the Type A medicated article label to include an extralabel
use statement (see proposed Sec. 201.409(a)(6)). Extralabel use of an
approved new animal drug or human drug in or on an animal feed is not
permitted (see section 512(a)(4) of the FD&C Act and part 530). The
required statement would be: ``It is a violation of Federal law to use
other than as directed in the labeling.'' It is important for the
layperson and veterinarian to know that it is a violation of Federal
law to use new animal drugs in or on animal feeds in an extralabel
manner.
g. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the Type A medicated article label
to have the heading ``Active Ingredient'' or ``Active Ingredients,''
followed by the established name and concentration of each active
ingredient in the Type A medicated article (see proposed Sec.
201.409(a)(7)). If the Type A medicated article contains one active
ingredient, the proposed rule would require this section of the Type A
medicated article label to be entitled ``Active Ingredient.'' If the
Type A medicated article contains more than one active ingredient, the
proposed rule would require this section of the Type A medicated
article label to be entitled ``Active Ingredients.'' Including the
concentration of the active ingredient(s) is critical so that feed
manufacturers can properly mix Type B and C medicated feeds from the
Type A medicated article with the approved concentration(s) of the
active ingredient(s).
h. ``Inactive Ingredients.'' When inactive ingredients are provided
on the Type A medicated article label, the proposed rule would require
they be listed in the ``Inactive Ingredients'' section in decreasing
order of predominance, by weight or concentration, as described in
proposed Sec. 201.405(a)(6)(viii) for full prescribing information for
Rx new animal drugs (see proposed Sec. 201.409(a)(8)).
i. ``Directions.'' The proposed rule would require this section of
the Type A medicated article label to have the heading ``Directions,''
followed by the directions for use of the Type A medicated article (see
proposed Sec. 201.409(a)(9)). The ``Directions'' section of the Type A
medicated article label would include three subsections.
i. ``Approved Concentration(s) of [Active Ingredient or Active
Moiety] in Type C Medicated Feeds.'' The proposed rule would require
the first subsection of the ``Directions'' section of the Type A
medicated article label to have the heading ``Approved Concentration(s)
of [Active Ingredient or Active Moiety] in Type C Medicated Feeds,''
followed by the approved concentration(s) of each active ingredient in
Type C medicated feed(s) to be manufactured from the Type A medicated
article for the approved or conditionally approved indications for use
(see proposed Sec. 201.409(a)(9)(i)). If an active ingredient is a
salt or other noncovalent derivative, its concentration in the Type A
medicated article in the ``Active Ingredient'' or ``Active
Ingredients'' section (see proposed Sec. 201.409(a)(7)) may be
expressed on the basis of the full active ingredient (i.e., including
the salt or other noncovalent derivative) or the active moiety. If an
active ingredient is a salt or other noncovalent derivative and its
concentration in the Type A medicated article was expressed in the
``Active Ingredient'' or Active Ingredients'' section based on the
active moiety, the proposed rule would require the approved
concentration(s) in the Type C medicated feeds to also be expressed
based on the active moiety, and the title of this subsection would be
required to include the name of the active moiety instead of the active
ingredient (see proposed Sec. 201.409(a)(9)(i)). Consistent expression
of the concentrations of active ingredients on the Type A medicated
article label may reduce the risk of mixing errors when manufacturing
medicated feeds from the Type A medicated article.
Multiple Type C medicated feeds may be approved or conditionally
approved for a Type A medicated article. Also, different
concentrations, or ranges of concentrations, of the active ingredient
may be approved or conditionally approved for different indications for
use. This subsection of the Type A medicated article label would
clarify this information for manufacturers of medicated feeds
manufactured from the Type A medicated article.
ii. ``Mixing Directions.'' The proposed rule would require this
subsection of the ``Directions'' section of the Type A medicated
article label to have the heading ``Mixing Directions,'' followed by
the approved mixing directions for the manufacture of approved
medicated feeds from the Type A medicated article for each approved or
conditionally approved indication for use (see proposed Sec.
201.409(a)(9)(ii)). An intermediate mixing step (called preblend step)
is sometimes required to manufacture medicated feeds from the Type A
medicated article. For example, the Type A medicated article may need
to be preblended with a small amount of one or more feed ingredients
before being added to the rest of the feed ingredients to increase the
uniformity of the drug distribution in the finished medicated feed. The
directions for such a preblend step would also be required to be
included in this subsection of the Type A medicated article label.
iii. ``Feeding Directions.'' The proposed rule would require the
last subsection in the ``Directions'' section of the Type A medicated
article label to have the heading ``Feeding Directions,'' followed by
the approved feeding directions for each approved or conditionally
approved indication for use for Type C medicated feeds approved or
conditionally approved to be manufactured from the Type A medicated
article (see proposed Sec. 201.409(a)(9)(iii)).
j. ``Warnings.'' The proposed rule would require this section of
the Type A medicated article label for all approved or conditionally
approved Type A medicated articles, and it would have the heading
``Warnings,'' followed by all warnings (see proposed Sec.
201.409(a)(10)). This section of the Type A medicated article label
would have the same subsections as described in Sec. 201.405(a)(10) in
full prescribing information for Rx new animal drugs, except that the
``Animal Safety Warnings'' subsection would be the same as described in
proposed Sec. 201.407(a)(7)(iii) for full product information for OTC
new animal drugs.
k. ``Additional Recommendations.'' For new animal drugs having
precautions, the proposed rule would require this section of the Type A
medicated article label to have the heading ``Additional
Recommendations,'' followed by all precautions (see proposed Sec.
201.409(a)(11)). This section of the Type A medicated article label
would be
[[Page 18298]]
the same as described in proposed Sec. 201.407(a)(8) for full product
information for OTC new animal drugs. For VFD new animal drugs, this
section would include precautions directed to veterinarians as well as
the layperson.
l. ``Other Effects You May Notice.'' For new animal drugs that have
effects on the target animal(s) that are not considered
contraindications, target animal safety warnings, adverse reactions, or
post-approval adverse drug experiences, and FDA determines that these
effects are required to be described on labeling, the proposed rule
would require this section of the Type A medicated article label to
have the heading ``Other Effects You May Notice,'' followed by a
description of the effects (see proposed Sec. 201.409(a)(12)). This
section of the Type A medicated article label would be the same as
described in proposed Sec. 201.407(a)(9) for full product information
for OTC new animal drugs.
m. ``Net Weight.'' The proposed rule would require this section of
the Type A medicated article label to have the heading ``Net Weight,''
followed by the net weight of the Type A medicated article in the
immediate container (see proposed Sec. 201.409(a)(13)).
n. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the Type A medicated article label to have the
heading ``Storage, Handling, and Disposal,'' followed by storage
information for the Type A medicated article, as well as any required
handling and disposal information (see proposed Sec. 201.409(a)(14)).
This section of the Type A medicated article label would be the same as
described in proposed Sec. 201.405(a)(20) for full prescribing
information for Rx new animal drugs.
o. ``Questions/Comments?'' The proposed rule would require this
section of the Type A medicated article label to have the heading
``Questions/Comments?,'' followed by the sponsor's contact information
for feed manufacturers or other users of the Type A medicated article
to facilitate requesting additional information or to report suspected
adverse drug experiences. FDA's contact information for voluntary
reporting of adverse drug experiences for animal drugs would also be
required (see proposed Sec. 201.409(a)(15)). The ``Questions/
Comments?'' section of the Type A medicated article label would be
similar to the ``Questions/Comments?'' section in proposed Sec.
201.407(a)(14) for full product information for OTC new animal drugs.
The sponsor's contact information would be the name of the
manufacturer, packer, or distributor, whichever is identified in the
``Name and place of business'' section of the Type A medicated article
label (see proposed Sec. 201.409(a)(17)). If more than one business is
identified in the ``Name and place of business'' section of the Type A
medicated article label, the drug sponsor would select the most
appropriate of these businesses to use in the ``Questions/Comments?''
section to provide additional information about the Type A medicated
article and to contact regarding suspected adverse drug experiences.
The statements in this section of the Type A medicated article
label would be required to be structured as follows: ``Contact [insert
name of business] at [insert business telephone number] or [insert
business web address]. To report side effects, contact [insert name of
business] at [insert business telephone number]. For additional
information about reporting side effects for animal drugs, contact FDA
at [insert current FDA telephone number for voluntary reporting of
adverse drug experiences] or [insert current FDA web address for
voluntary reporting of adverse drug experiences].'' Sponsors can search
FDA's website or contact FDA by telephone to find the current FDA
telephone number or web address for voluntary reporting of adverse drug
experiences for animal drug.
p. NADA/ANADA approval statement. For approved or generic approved
Type A medicated articles, the proposed rule would require this section
of the Type A medicated article label to include an ``NADA approval
statement'' or ``ANADA approval statement,'' respectively (see proposed
Sec. 201.409(a)(16)). This section of the Type A medicated article
label would be the same as described in proposed Sec. 201.405(a)(21)
for full prescribing information for Rx new animal drugs.
q. Name and place of business. The proposed rule would require this
section of the Type A medicated article label to identify the name and
place of business of the manufacturer, packer, or distributor (see
proposed Sec. 201.409(a)(17)). This section of the Type A medicated
article label would be the same as described in proposed Sec.
201.405(a)(22) for full prescribing information for Rx new animal
drugs.
r. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the Type A medicated article label to have the
heading ``Lot Number and Expiration Date,'' followed by the identifying
lot or control number of the Type A medicated article within the
immediate container. A lot or control number would help us to more
easily identify and trace back a specific lot of a Type A medicated
article should a problem be reported to FDA (see proposed Sec.
201.409(a)(18)). In accordance with Sec. 226.58(d) of this chapter,
the proposed rule would also require this section of the Type A
medicated article label to include the expiration date of the Type A
medicated article within the immediate container. An expiration date is
important to ensure the safe and effective use of products.
Alternatively, the proposed rule would allow for this section of
the Type A medicated article label to refer to the location on the Type
A medicated article label or immediate container where the lot or
control number and expiration date are printed (see proposed Sec.
201.409(a)(18)). As an example, if the lot number and expiration date
are printed on the bottom half of the back of the bag containing the
Type A medicated article, then the Type A medicated article label may
state in this section, ``See bottom back half of bag for lot number and
expiration date.''
s. ``Revision Date.'' The proposed rule would require this section
of the Type A medicated article label to have the heading ``Revision
Date,'' followed by the date of the most recent revision of the Type A
medicated article label, listing the month followed by the year (see
proposed Sec. 201.409(a)(19)). This information is important to ensure
that the most current approved version of the Type A medicated article
label is being used.
2. Representative Type B Medicated Feed Labeling (Proposed Sec.
201.409(b))
The proposed rule would establish content and format requirements
for representative Type B medicated feed labeling for new animal drugs
approved or conditionally approved for use in animal feeds (see
proposed Sec. 201.409(b)). A Type B medicated feed is intended solely
for the manufacture of other medicated feeds (Type B or Type C). It
serves as an intermediate medicated feed not approved for feeding to
the target animals. It is manufactured by diluting a Type A medicated
article or another Type B medicated feed with non-medicated feed, and
at least 25 percent of its weight is from nutritional ingredients (see
Sec. 558.3(b)(3)). Representative Type B medicated feed labeling is
template labeling approved by FDA as part of an NADA or CNADA for a
Type A medicated article.
Representative Type B medicated feed labeling approved in the NADA
or CNADA provide feed mills the minimal information that must be
included on
[[Page 18299]]
the final printed labels prepared for the Type B medicated feeds
manufactured containing the Type A medicated article to provide for
safe and effective use of the new animal drug for its approved or
conditionally approved indication(s) for use.
The proposed rule would require the following information to be
presented on the representative Type B medicated feed labeling for an
approved or conditionally approved new animal drug and in the following
order (see proposed Sec. 201.409(b)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs, proposed Sec. 201.407(a)
for full product information for approved or conditionally approved OTC
new animal drugs, or proposed Sec. 201.409(a) for the Type A medicated
article label.
a. Description of the Type B medicated feed. The proposed rule
would require this section of the representative Type B medicated feed
labeling to provide a description of the Type B medicated feed (see
proposed Sec. 201.409(b)(1)). This section of the representative Type
B medicated feed labeling would serve as a placeholder for the
proprietary name of the final Type B medicated feed to be added by the
feed manufacturer to the label of the final Type B medicated feed
manufactured in accordance with the approved representative Type B
labeling.
Representative Type B medicated labeling may be approved or
conditionally approved for multiple Type B medicated feeds within an
application. The proposed rule would require the description of each
approved Type B medicated feed to distinguish it from any other Type B
medicated feeds approved or conditionally approved within the same
application (see proposed Sec. 201.409(b)(1)(i)). Distinguishing
information may include the animals and/or indications for use for
which Type C medicated feeds manufactured from the Type B medicated
feed are approved or conditionally approved and/or other
characteristics of the Type B medicated feeds.
The proposed rule would require that the description of the
approved Type B medicated feed not include the proprietary name of a
Type A medicated article (see proposed Sec. 201.409(b)(1)(ii)). The
proprietary name of a Type A medicated article is specific to the Type
A medicated article; use of that proprietary name in the description of
a Type B medicated feed may incorrectly imply that the Type B medicated
feed is a Type A medicated article.
b. Established name of the Type B medicated feed. The proposed rule
would require this section of the representative Type B medicated feed
labeling to include the established name of the Type B medicated feed.
The established name of the Type B medicated feed would include the
active moiety or active ingredient of each new animal drug, as
determined by FDA, followed by an identifying statement of either
``Type B medicated feed'' or ``Type B liquid medicated feed,'' as
applicable (see proposed Sec. 201.409(b)(2)). The identifying
statements also clearly designate the medicated feeds as Type B (as
opposed to a Type C) medicated feeds. The identifying statements also
distinguish Type B liquid medicated feeds from other Type B medicated
feeds, which is important because Type B liquid medicated feeds have
unique approval and labeling requirements (see Sec. 558.5 (21 CFR
558.5)).
c. VFD cautionary statement. For VFD new animal drugs, the proposed
rule would require this section of the representative Type B medicated
feed labeling to provide the VFD cautionary statement, in accordance
with Sec. 558.6(a)(6), as described in proposed Sec. 201.409(a)(2)
for the Type A medicated article label (see proposed Sec.
201.409(b)(3)).
d. ``Do Not Feed Undiluted.'' The proposed rule would require this
section of the representative Type B medicated feed labeling to state,
``Do Not Feed Undiluted'' (see proposed Sec. 201.409(b)(4)). This
statement would remind users that the Type B medicated feed is not to
be fed directly to animals.
e. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the
representative Type B medicated feed labeling to include a conditional
approval statement, as described in proposed Sec. 201.405(a)(3) for
full prescribing information for Rx new animal drugs (see proposed
Sec. 201.409(b)(5)).
f. ``Indications for Use.'' The proposed rule would require this
section of the representative Type B medicated feed labeling to have
the heading ``Indications for Use,'' followed by the approved or
conditionally approved indications(s) and target animal(s), as
described in proposed Sec. 201.407(a)(3) for full product information
for OTC new animal drugs, with the exception of the heading. In
addition, this section of the representative Type B medicated feed
labeling would include only the indications for use applicable to the
specific Type B medicated feed to which the representative labeling
applies (see proposed Sec. 201.409(b)(6)).
g. Extralabel use statement. The proposed rule would require this
section of the representative Type B medicated feed labeling to include
an extralabel use statement, as described in proposed Sec.
201.409(a)(6) for the Type A medicated article label (see proposed
Sec. 201.409(b)(7)).
h. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the representative Type B medicated
feed labeling to have the heading ``Active Ingredient'' or ``Active
Ingredients,'' followed by the established name and approved
concentration(s) of each active ingredient (see proposed Sec.
201.409(b)(8)). If the Type B medicated feed contains one active
ingredient, the proposed rule would require this section of the
representative Type B medicated feed labeling to be titled ``Active
Ingredient.'' If the Type B medicated feed contains more than one
active ingredient, the proposed rule would require this section of the
representative Type B medicated feed labeling to be titled ``Active
Ingredients.'' FDA approves a single concentration or a range of
concentrations of each active ingredient for Type B medicated feeds and
their representative Type B medicated feed labeling. However, the final
Type B medicated feed label would only include a single concentration
of each active ingredient. If a range of concentrations of the active
ingredient(s) is approved or conditionally approved for Type B
medicated feeds, the representative Type B medicated feed labeling
would be required to include a footnote, placed at the bottom of the
page of the representative Type B medicated feed labeling containing
the ``Active Ingredient'' or ``Active Ingredients'' section, which
instructs feed manufacturers that the final printed Type B medicated
feed label must only include a single concentration for each active
ingredient.
i. ``Guaranteed Analysis.'' The proposed rule would require this
section of the representative Type B medicated feed labeling to have
the heading ``Guaranteed Analysis,'' followed by the nutritional
content guarantees of the Type B medicated feed appropriate for the
approved target animals in addition to any other required
specifications (see proposed Sec. 201.409(b)(9)). The Type B medicated
feed will be used to make a Type C medicated feed that will be included
as part of the target animals' diet or serve
[[Page 18300]]
as their complete diet. Therefore, the feed manufacturer and user must
be aware of the nutritional content of the Type B medicated feed to
properly balance the nutritional content of the diet of the target
animal. Without this nutritional content information being made
available to the manufacturer and user of the medicated feed, the
animals' diet may be imbalanced, e.g., either under- or over-feeding
critical nutrients, which could be harmful to the health of the target
animals. For this reason, information of this type may be considered
material under section 201(n) of the FD&C Act such that it would be
required to be disclosed on the representative Type B feed labeling.
Additional specifications may also be required in this section of
the representative Type B medicated feed labeling, such as the range of
pH and/or range of percent dry matter. For example, the pH and/or ratio
of dry matter to moisture (expressed as percent dry matter) of a liquid
medicated feed may affect the stability of the new animal drug(s) it
contains, such that a specific Type B liquid medicated feed would be
approved only within a specific range of pH and/or percent dry matter
(see Sec. 558.5(d)(1) and (2)).
j. ``Ingredients.'' The proposed rule would require this section of
the representative Type B medicated feed labeling to have the heading
``Ingredients,'' followed by information relative to feed ingredients
(see proposed Sec. 201.409(b)(10)). This information would include a
statement that the feed ingredients must be listed on each final
printed Type B medicated feed label by their common or usual names in
descending order of predominance by weight, in accordance with Sec.
501.4(a) (21 CFR 501.4(a)), including their collective names where
permitted, in accordance with Sec. 501.4(b)(13). Also included would
be a statement that spices, flavorings, colorings, and chemical
preservatives, if used, must be declared on each final printed Type B
medicated feed label, in accordance with Sec. 501.22 (21 CFR 501.22).
k. ``Mixing Directions.'' The proposed rule would require this
section of the representative Type B medicated feed labeling to have
the heading ``Mixing Directions,'' followed by approved mixing
directions for the manufacture of a Type C medicated feed(s) or another
Type B medicated feed(s), as applicable, from the Type B medicated feed
for which the representative Type B medicated feed labeling applies
(see proposed Sec. 201.409(b)(11)).
l. ``Warnings.'' The proposed rule would require this section of
the representative Type B medicated feed labeling to have the heading
``Warnings,'' followed by the ``Warnings'' section, as described in
proposed Sec. 201.409(a)(10) for the Type A medicated article label.
In addition, this section of the representative Type B medicated feed
labeling would include only the warnings applicable to the specific
Type B medicated feed to which the representative labeling applies (see
proposed Sec. 201.409(b)(12)).
m. ``Additional Recommendations.'' For new animal drugs having
precautions, the proposed rule would require this section of the
representative Type B medicated feed labeling to have the heading
``Additional Recommendations,'' followed by the precautions, as
described in proposed Sec. 201.407(a)(8) for full product information
for OTC new animal drugs. In addition, this section of the
representative Type B medicated feed labeling would include only the
precautions applicable to the specific Type B medicated feed to which
the representative labeling applies (see proposed Sec.
201.409(b)(13)).
n. ``Other Effects You May Notice.'' For new animal drugs that have
effects on the target animal(s) that are not considered
contraindications, target animal safety warnings, adverse reactions, or
post-approval adverse drug experiences, and FDA determines that these
effects are required to be described on labeling, the proposed rule
would require this section of the representative Type B medicated feed
labeling to have the heading ``Other Effects You May Notice,'' followed
by a description of the effects. This section of the representative
Type B medicated feed labeling would be the same as described in
proposed Sec. 201.407(a)(9) for full product information for OTC new
animal drugs. In addition, this section of the representative Type B
medicated feed labeling would include only statements of other effects
applicable to the specific Type B medicated feed to which the
representative Type B medicated feed labeling applies (see proposed
Sec. 201.409(b)(14)).
o. Name and place of business. The proposed rule would require this
section of the representative Type B medicated feed labeling to provide
for identification of the name and place of business of the
manufacturer, packer, or distributor of the final Type B medicated feed
on the final printed Type B medicated feed label, in accordance with
Sec. 501.5 (see proposed Sec. 201.409(b)(15)).
p. ``Net Weight.'' The proposed rule would require this section of
the representative Type B medicated feed labeling to have the heading
``Net Weight,'' followed by space to provide for a statement on the
final printed Type B medicated feed label of the net weight of the Type
B medicated feed in the immediate container (see proposed Sec.
201.409(b)(16)).
q. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the representative Type B medicated feed
labeling to have the heading ``Storage, Handling, and Disposal,''
followed by storage information for the Type B medicated feed, as well
as any required handling and disposal information, as described in
proposed Sec. 201.405(a)(20) for full prescribing information for Rx
new animal drugs (see proposed Sec. 201.409(b)(17)).
r. ``Questions/Comments?'' The proposed rule would require this
section of the representative Type B medicated feed labeling to have
the heading ``Questions/Comments?,'' followed by statements providing
contact information for use by feed manufacturers or other users of the
final Type B medicated feed to request additional information on the
product and/or to report problems with the medicated feed (see proposed
Sec. 201.409(b)(18)). The first statement would provide placeholders
for the name and contact information of the business of the
manufacturer, packer, or distributor of the final Type B medicated feed
to later be inserted by the business. The second statement would
provide FDA contact information for reporting adverse drug experiences
for animal drugs and would be required to be inserted by the sponsor of
the new animal drug application.
s. ``Lot, Batch, or Control Number.'' The proposed rule would
require this section of the representative Type B medicated feed
labeling to have the heading ``Lot, Batch, or Control Number,''
followed by space to provide for an identifying lot, batch, or control
number on the final printed Type B medicated feed label (see proposed
Sec. 201.409(b)(19)).
t. ``Expiration Date.'' For Type B medicated feeds requiring an
expiration date, in accordance with Sec. 514.1(b)(5)(x), the proposed
rule would require this section of the representative Type B medicated
feed labeling to have the heading ``Expiration Date,'' followed by
space to provide for the expiration date to be printed on the final
printed Type B medicated feed label. In addition, the approved
expiration period would need to be included in this section of the
representative Type B medicated feed labeling (see proposed Sec.
201.409(b)(20)).
[[Page 18301]]
u. ``Revision Date.'' The proposed rule would require this section
of the representative Type B medicated feed labeling to have the
heading ``Revision Date,'' followed by the date of the most recent
revision of the representative Type B medicated feed labeling, listing
the month followed by the year (see proposed Sec. 201.409(b)(21)).
This information is important to ensure that the most current approved
version of the representative Type B medicated feed labeling is being
used.
3. Representative Type C Medicated Feed Labeling (Proposed Sec.
201.409(c))
The proposed rule would establish content and format requirements
for representative Type C medicated feed labeling for new animal drugs
approved or conditionally approved for use in animal feeds (see
proposed Sec. 201.409(c)). Type C medicated feed is fed directly to
target animals. It may also be used in the manufacture of another Type
C medicated feed. When fed directly to target animals, it is intended
to be the animals' complete feed or part of their total diet. It is
manufactured by diluting a Type A medicated article, a Type B medicated
feed, or another Type C medicated feed with non-medicated feed, and it
contains a substantial quantity of nutritional ingredients (see Sec.
558.3(b)(4)).
Representative Type C medicated feed labeling approved in the NADA
or CNADA provide feed mills the minimal information that must be
included on the final printed labels prepared for the Type C medicated
feeds manufactured containing the Type A medicated article to provide
for safe and effective use of the new animal drug for its approved or
conditionally approved indication(s) for use.
The proposed rule would require the following information to be
presented on the representative Type C medicated feed labeling for an
approved or conditionally approved new animal drug and in the following
order (see proposed Sec. 201.409(c)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs, proposed Sec. 201.407(a)
for full product information for approved or conditionally approved OTC
new animal drugs, proposed Sec. 201.409(a) for the Type A medicated
article label, or proposed Sec. 201.409(b) for representative Type B
medicated feed labeling.
a. Description of the Type C medicated feed. The proposed rule
would require this section of the representative Type C medicated feed
labeling to provide a description of the Type C medicated feed (see
proposed Sec. 201.409(c)(1)). This section of the representative Type
C medicated feed labeling would serve as a placeholder for the
proprietary name of the final Type C medicated feed to be added by the
feed manufacturer to the label of the final Type C medicated feed
manufactured in accordance with the approved representative Type C
labeling.
Representative Type C medicated labeling may be approved or
conditionally approved for multiple Type C medicated feeds within an
application. The proposed rule would require the description of each
approved Type C medicated feed to distinguish it from any other Type C
medicated feeds approved or conditionally approved within the same
application (see proposed Sec. 201.409(c)(1)(i)). Distinguishing
information may include the animals and/or indications for use for
which Type C medicated feeds are approved or conditionally approved
and/or other characteristics of the Type C medicated feeds.
The proposed rule would require that the description of the
approved Type C medicated feed not include the proprietary name of a
Type A medicated article (see proposed Sec. 201.409(c)(1)(ii)). The
proprietary name of a Type A medicated article is specific to the Type
A medicated article; use of that proprietary name in the description of
a Type C medicated feed may incorrectly imply that the Type C medicated
feed is a Type A medicated article.
b. Established name of the Type C medicated feed. The proposed rule
would require this section of the representative Type C medicated feed
labeling to include the established name of the Type C medicated. The
established name of the Type C medicated feed would include the active
moiety or active ingredient of each new animal drug, as determined by
FDA, followed by an identifying statement of, ``Type C medicated
feed,'' ``Type C liquid medicated feed,'' ``Type C top-dress medicated
feed,'' ``Type C free-choice medicated feed,'' or ``Type C liquid free-
choice medicated feed,'' as applicable (see proposed Sec.
201.409(c)(2)). The identifying statements also clearly designate the
medicated feeds as Type C (as opposed to a Type B) medicated feeds. The
identifying statements also distinguish Type C liquid medicated feeds
from other Type C medicated feeds, which is important because Type C
liquid medicated feeds have unique approval and labeling requirements
(see Sec. 558.5). Similarly, Type C free-choice medicated feeds have
specific requirements for their approval (see Sec. 510.455 (21 CFR
510.455)).
c. VFD cautionary statement. For VFD new animal drugs, the proposed
rule would require this section of the representative Type C medicated
feed labeling to provide the VFD cautionary statement, in accordance
with Sec. 558.6(a)(6), as described in proposed Sec. 201.409(a)(2)
for the Type A medicated article label (see proposed Sec.
201.409(c)(3)).
d. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the
representative Type C medicated feed labeling to include a conditional
approval statement, as described in proposed Sec. 201.405(a)(3) for
full prescribing information for Rx new animal drugs (see proposed
Sec. 201.409(c)(4)).
e. ``Indications for Use.'' The proposed rule would require this
section of the representative Type C medicated feed labeling to have
the heading ``Indications for Use,'' followed by the approved or
conditionally approved indications(s) and target animal(s), as
described in proposed Sec. 201.407(a)(3) for full product information
for OTC new animal drugs, with the exception of the heading. In
addition, this section of the representative Type C medicated feed
labeling would include only the indications for use applicable to the
specific Type C medicated feed to which the representative labeling
applies (see proposed Sec. 201.409(c)(5)).
f. Extralabel use statement. The proposed rule would require this
section of the representative Type C medicated feed labeling to include
an extralabel use statement, as described in proposed Sec.
201.409(a)(6) for the Type A medicated article label (see proposed
Sec. 201.409(c)(6)).
g. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the representative Type C medicated
feed labeling to have the heading ``Active Ingredient'' or ``Active
Ingredients,'' followed by the established name and approved
concentration(s) of each active ingredient (see proposed Sec.
201.409(c)(7)). If the Type C medicated feed contains one active
ingredient, the proposed rule would require this section of the
representative Type C medicated feed labeling to be entitled ``Active
Ingredient.'' If the Type C medicated feed contains more than one
active ingredient, the proposed rule would require this section of the
representative Type C medicated feed
[[Page 18302]]
labeling to be entitled ``Active Ingredients.'' We approve a single
concentration or a range of concentrations of each active ingredient
for Type C medicated feeds and their representative Type C medicated
feed labeling. However, the final Type C medicated feed label would
only include a single concentration of each active ingredient. If a
range of concentrations of the active ingredient(s) is approved or
conditionally approved for Type C medicated feeds, the representative
Type C medicated feed labeling would be required to include a footnote,
placed at the bottom of the page of the representative Type C medicated
feed labeling containing the ``Active Ingredient'' or ``Active
Ingredients'' section, which instructs feed manufacturers that the
final printed Type C medicated feed label must include only a single
concentration for each active ingredient.
h. ``Guaranteed Analysis.'' The proposed rule would require this
section of the representative Type C medicated feed labeling to have
the heading ``Guaranteed Analysis,'' followed by the nutritional
content guarantees of the Type C medicated feed and any other required
specifications, as described in proposed Sec. 201.409(b)(9) for
representative Type B medicated feed labeling (see proposed Sec.
201.409(c)(8)).
i. ``Ingredients.'' The proposed rule would require this section of
the representative Type C medicated feed labeling to have the heading
``Ingredients,'' followed by information relative to feed ingredients
(see proposed Sec. 201.409(c)(9)).
For Type C medicated feeds that are not Type C free-choice
medicated feeds, proposed Sec. 201.409(b)(9)(i) would require the
heading to be followed by a statement that the feed ingredients must be
listed on each final printed Type C medicated feed label by their
common or usual names in descending order of predominance by weight, in
accordance with Sec. 501.4(a), including their collective names where
permitted, in accordance with Sec. 501.4(b)(13). Also included would
be a statement that spices, flavorings, colorings, and chemical
preservatives, if used, must be declared on the final printed Type C
medicated feed label, in accordance with Sec. 501.22.
For Type C free-choice medicated feeds, the proposed rule would
require the heading to be followed by a listing of the feed ingredients
and their inclusion rates, including the drug concentrations exactly as
they appear in the approved non-proprietary formula published for the
specific new animal drug in part 558 (see proposed Sec.
201.409(b)(9)(ii)).
j. ``Feeding Directions.'' The proposed rule would require this
section of the representative Type C medicated feed labeling to have
the heading ``Feeding Directions,'' followed by the approved feeding
directions (see proposed Sec. 201.409(c)(10)). This section of
representative Type C medicated feed labeling would include only the
feeding directions applicable to the specific Type C medicated feed to
which the representative Type C medicated feed labeling applies.
k. ``Warnings.'' The proposed rule would require this section of
the representative Type C medicated feed labeling to have the heading
``Warnings,'' followed by the ``Warnings'' section, as described in
proposed Sec. 201.409(a)(10) for the Type A medicated article label.
In addition, this section of the representative Type C medicated feed
labeling would include only the warnings applicable to the specific
Type C medicated feed to which the representative labeling applies (see
proposed Sec. 201.409(c)(11)).
l. ``Additional Recommendations.'' For new animal drugs having
precautions, the proposed rule would require this section of the
representative Type C medicated feed labeling to have the heading
``Additional Recommendations,'' followed by the precautions, as
described in proposed Sec. 201.407(a)(8) for full product information
for OTC new animal drugs. In addition, this section of the
representative Type C medicated feed labeling would include only the
precautions applicable to the specific Type C medicated feed to which
the representative labeling applies (see proposed Sec.
201.409(c)(12)).
m. ``Other Effects You May Notice.'' For new animal drugs that have
effects on the target animal(s) that are not considered
contraindications, target animal safety warnings, adverse reactions, or
post-approval adverse drug experiences, and FDA determines that these
effects are required to be described on labeling, the proposed rule
would require this section of the representative Type C medicated feed
labeling to have the heading ``Other Effects You May Notice,'' followed
by a description of the effects. This section of the representative
Type C medicated feed labeling would be the same as described in
proposed Sec. 201.407(a)(9) for full product information for OTC new
animal drugs. In addition, this section of the representative Type C
medicated feed labeling would include only statements of other effects
applicable to the specific Type C medicated feed to which the
representative Type C labeling applies (see proposed Sec.
201.409(c)(13)).
n. Name and place of business. The proposed rule would require this
section of the representative Type C medicated feed labeling to provide
for identification of the name and place of business of the
manufacturer, packer, or distributor of the final Type C medicated feed
on the final printed Type C medicated feed label, in accordance with
Sec. 501.5 (see proposed Sec. 201.409(c)(14)).
o. ``Net Weight.'' The proposed rule would require this section of
the representative Type C medicated feed labeling to have the heading
``Net Weight,'' followed by space to provide for a statement on the
final printed Type C medicated feed label of the net weight of the Type
C medicated feed in the immediate container (see proposed Sec.
201.409(c)(15)).
p. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the representative Type C medicated feed
labeling to have the heading ``Storage, Handling, and Disposal,''
followed by storage information for the Type C medicated feed, as well
as any required, handling and disposal information, as described in
proposed Sec. 201.405(a)(20) for full prescribing information for Rx
new animal drugs (see proposed Sec. 201.409(c)(16)).
q. ``Questions/Comments?'' The proposed rule would require this
section of the representative Type C medicated feed labeling to have
the heading ``Questions/Comments?,'' followed by statements providing
contact information for use by feed manufacturers or other users of the
final Type C medicated feed to request additional information on the
product and/or to report problems with the medicated feed (see proposed
Sec. 201.409(c)(17)). The first statement would provide placeholders
for the name and contact information of the business of the
manufacturer, packer, or distributor of the final Type C medicated feed
to later be inserted by the business. The second statement would
provide FDA contact information for reporting adverse drug experiences
for animal drugs and would be required to be inserted by the sponsor of
the new animal drug application.
r. ``Lot, Batch, or Control Number.'' The proposed rule would
require this section of the representative Type C medicated feed
labeling to have the heading ``Lot, Batch, or Control Number,''
followed by space to provide for an identifying lot, batch, or control
[[Page 18303]]
number on the final printed Type C medicated feed label (see proposed
Sec. 201.409(c)(19)).
s. ``Expiration Date.'' For Type C medicated feeds requiring an
expiration date, in accordance with Sec. 514.1(b)(5)(x), the proposed
rule would require this section of the representative Type C medicated
feed labeling to have the heading ``Expiration Date,'' followed by
space to provide for the expiration date to be printed on the final
printed Type C medicated feed label. In addition, the approved
expiration period would need to be included in this section of the
representative Type C medicated feed labeling (see proposed Sec.
201.409(c)(19)).
t. ``Revision Date.'' The proposed rule would require this section
of the representative Type C medicated feed labeling to have the
heading ``Revision Date,'' followed by the date of the most recent
revision of the representative Type C medicated feed labeling, listing
the month followed by the year (see proposed Sec. 201.409(c)(20)).
This information is important to ensure that the most current approved
version of the representative Type C medicated feed labeling is being
used.
4. Proprietary Type B Medicated Feed Label (Proposed Sec. 201.409(d))
The proposed rule would establish content and format requirements
for a proprietary Type B medicated feed label for new animal drugs
approved or conditionally approved for use in animal feeds (see
proposed Sec. 201.409(d)). A proprietary Type B medicated feed is
intended solely for the manufacture of Type C medicated feeds or other
Type B medicated feeds and is not approved or conditionally approved
for feeding to the target animals. For some proprietary Type B
medicated feeds, the formulation and labeling are approved in an NADA.
In other situations, the underlying data and labeling for the
proprietary Type B medicated feed to support the approved uses are
maintained in a VMF. For example, this would include situations in
which a proprietary Type B medicated feed is manufactured via
modification to an approved formulation published in the CFR or where a
feed manufacturer creates its own proprietary formulation. The
application for a proprietary Type B medicated feed will include the
proprietary label for the final Type B medicated feed and
representative Type C medicated feed labeling that directs the
preparation of final printed labels for Type C medicated feeds
manufactured from the proprietary Type B medicated feed. A proprietary
Type B medicated feed label is on the immediate container, which is
typically a bag or bulk container.
The proposed rule would require the following information to be
presented on the proprietary Type B medicated feed label for an
approved or conditionally approved new animal drug and in the following
order (see proposed Sec. 201.409(d)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs, proposed Sec. 201.407(a)
for full product information for approved or conditionally approved OTC
new animal drugs, or proposed Sec. 201.409(a) for the Type A medicated
article label.
a. Proprietary Type B medicated feed identification. The proposed
rule would require this section of the proprietary Type B medicated
feed label to identify the Type B medicated feed (see proposed Sec.
201.409(d)(1)). This section of the proprietary Type B medicated feed
label would be required to include the following components in order:
i. Proprietary name of the Type B medicated feed. The proposed rule
require this subsection of the proprietary Type B medicated feed label
to include the proprietary name of the Type B medicated feed (see
proposed Sec. 201.409(d)(1)(i)).
ii. Established name of the Type B medicated feed. The proposed
rule would require this subsection of the proprietary Type B medicated
feed label to include the established name of the Type B medicated
feed. The established name of the Type B medicated feed would include
the active moiety or active ingredient of each new animal drug, as
determined by FDA, followed by an identifying statement of either
``Type B medicated feed'' or ``Type B liquid medicated feed,'' as
applicable (see proposed Sec. 201.409(d)(1)(ii)). The identifying
statements also clearly designate the medicated feed as a Type B (as
opposed to a Type C) medicated feed. The identifying statements also
distinguish Type B liquid medicated feeds from other Type B medicated
feeds, which is important because Type B liquid medicated feeds have
unique approval and labeling requirements (see Sec. 558.5).
b. VFD cautionary statement. For VFD new animal drugs, the proposed
rule would require this section of the proprietary Type B medicated
feed label to provide the VFD cautionary statement, in accordance with
Sec. 558.6(a)(6), as described in proposed Sec. 201.409(a)(2) for the
Type A medicated article label (see proposed Sec. 201.409(d)(2)).
c. ``Do Not Feed Undiluted.'' The proposed rule would require this
section of the proprietary Type B medicated feed label to state, ``Do
Not Feed Undiluted'' (see proposed Sec. 201.409(d)(3)). This statement
would remind users that the Type B medicated feed is not to be fed
directly to animals.
d. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the
proprietary Type B medicated feed label to include a conditional
approval statement, as described in proposed Sec. 201.405(a)(3) for
full prescribing information for Rx new animal drugs (see proposed
Sec. 201.409(d)(4)).
e. ``Indications for Use.'' The proposed rule would require this
section of the proprietary Type B medicated feed label to have the
heading ``Indications for Use,'' followed by the approved or
conditionally approved indications(s) and target animal(s), as
described in proposed Sec. 201.407(a)(3) for full product information
for OTC new animal drugs, with the exception of the heading (see
proposed Sec. 201.409(d)(5)).
f. Extralabel use statement. The proposed rule would require this
section of the proprietary Type B medicated feed label to include an
extralabel use statement, as described in proposed Sec. 201.409(a)(6)
for the Type A medicated article label (see proposed Sec.
201.409(d)(6)).
g. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the proprietary Type B medicated
feed label to have the heading ``Active Ingredient'' or ``Active
Ingredients,'' followed by the established name and approved
concentration of each active ingredient (see proposed Sec.
201.409(d)(7)). If the proprietary Type B medicated feed contains one
active ingredient, the proposed rule would require this section of the
proprietary Type B medicated feed label to be entitled ``Active
Ingredient.'' If the proprietary Type B medicated feed contains more
than one active ingredient, the proposed rule would require this
section of the proprietary Type B medicated feed label to be entitled
``Active Ingredients.'' Because the proprietary Type B medicated feed
label applies to a final Type B medicated feed, a single concentration
would be required for each active ingredient rather than a range.
h. ``Guaranteed Analysis.'' The proposed rule would require this
section of the proprietary Type B
[[Page 18304]]
medicated feed label to have the heading ``Guaranteed Analysis,''
followed by the nutritional content guarantees and any other required
specifications for the proprietary Type B medicated feed (see proposed
Sec. 201.409(d)(8)).
i. ``Ingredients.'' The proposed rule would require this section of
the proprietary Type B medicated feed label to have the heading
``Ingredients,'' followed by a listing of the feed ingredients in the
proprietary Type B medicated feed. The feed ingredients would be
required to be listed by their common or usual names in descending
order of predominance by weight, in accordance with Sec. 501.4(a),
including their collective names where permitted, in accordance with
Sec. 501.4(b)(13) (see proposed Sec. 201.409(d)(9)(i)). Spices,
flavorings, colorings, and chemical preservatives, if used, would be
required to be declared, in accordance with Sec. 501.22 (see proposed
Sec. 201.409(d)(9)(ii)).
j. ``Mixing Directions.'' The proposed rule would require this
section of the proprietary Type B medicated feed label to have the
heading ``Mixing Directions,'' followed by the approved mixing
directions for the manufacture of a Type C medicated feed(s) or another
Type B medicated feed(s), if applicable, from the proprietary Type B
medicated feed (see proposed Sec. 201.409(d)(10)).
k. ``Warnings.'' The proposed rule would require this section of
the proprietary Type B medicated feed label to have the heading
``Warnings,'' followed by the ``Warnings'' section, as described in
proposed Sec. 201.409(a)(10) for the Type A medicated article label
(see proposed Sec. 201.409(d)(11)).
l. ``Additional Recommendations.'' For new animal drugs having
precautions, the proposed rule would require this section of the
proprietary Type B medicated feed label to have the heading
``Additional Recommendations,'' followed by all precautions, as
described in proposed Sec. 201.407(a)(8) for full product information
for OTC new animal drugs (see proposed Sec. 201.409(d)(12)).
m. ``Other Effects You May Notice.'' For new animal drugs that have
effects on the target animal(s) that are not considered
contraindications, target animal safety warnings, adverse reactions, or
post-approval adverse drug experiences, and FDA determines that these
effects are required to be described on labeling, the proposed rule
would require this section of the proprietary Type B medicated feed
label to have the heading ``Other Effects You May Notice,'' followed by
a description of the effects. This section of the proprietary Type B
medicated feed label would be the same as described in proposed Sec.
201.407(a)(9) for full product information for OTC new animal drugs
(see proposed Sec. 201.409(d)(13)).
n. ``Net Weight.'' The proposed rule would require this section of
the proprietary Type B medicated feed label to have the heading ``Net
Weight,'' followed by the net weight of the Type B medicated feed in
the immediate container (see proposed Sec. 201.409(d)(14)).
o. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the proprietary Type B medicated feed label to
have the heading ``Storage, Handling, and Disposal,'' followed by
storage information for the Type B medicated feed, as well as any
required handling and disposal information, as described in proposed
Sec. 201.405(a)(20) for full prescribing information for Rx new animal
drugs (see proposed Sec. 201.409(d)(15)).
p. ``Questions/Comments?'' The proposed rule would require this
section of the proprietary Type B medicated feed label to have the
heading ``Questions/Comments?,'' followed by the sponsor's contact
information for feed manufacturers or other users of the Type B
medicated feed to facilitate requesting additional information on the
product or to report suspected adverse drug experiences. FDA's contact
information for voluntary reporting of adverse drug experiences for
animal drugs would also be required (see proposed Sec.
201.409(d)(16)).
The sponsor's contact information would be the name of the
manufacturer, packer, or distributor, whichever is identified in the
``Name and place of business'' section of the Type B medicated feed
(see proposed Sec. 201.409(d)(18)). If more than one business is
identified in the ``Name and place of business'' section of the
proprietary Type B medicated feed label, the drug sponsor would select
the most appropriate of these businesses to use in the ``Questions/
Comments?'' section to provide additional information about the Type B
medicated feed and to contact regarding suspected adverse drug
experiences.
The statements in this section of the proprietary Type B medicated
feed label would be required to be structured as follows: ``Contact
[insert name of business] at [insert business telephone number] or
[insert business web address]. To report side effects, contact [insert
name of business] at [insert business telephone number]. For additional
information about reporting problems with medicated feeds, contact FDA
at [insert current FDA telephone number for voluntary reporting of
adverse drug experiences] or [insert current FDA web address for
voluntary reporting of adverse drug experiences].'' Sponsors can search
FDA's website or contact FDA by telephone to find the current FDA
telephone number or web address for voluntary reporting of adverse drug
experiences for animal drug.
q. NADA/ANADA approval statement. For approved or generic approved
proprietary Type B medicated feeds, the proposed rule would require
this section of the proprietary Type B medicated feed label to include
an ``NADA approval statement'' or ``ANADA approval statement,''
respectively, as described in proposed Sec. 201.405(a)(21) for full
prescribing information for Rx new animal drugs (see proposed Sec.
201.409(d)(17)).
r. Name and place of business. The proposed rule would require this
section of the proprietary Type B medicated feed label to identify name
and place of business of the manufacturer, packer, or distributor, as
described in proposed Sec. 201.405(a)(22) for full prescribing
information for Rx new animal drugs (see proposed Sec.
201.409(d)(18)).
s. ``Lot, Batch, or Control Number.'' The proposed rule would
require this section of the proprietary Type B medicated feed label to
have the heading ``Lot, Batch, or Control Number,'' followed by the
identifying lot, batch, or control number of the Type B medicated feed.
Alternatively, the proposed rule would allow for this section of the
proprietary Type B medicated feed label to refer to the location on the
proprietary Type B medicated feed label or immediate container where
the lot, batch, or control number is printed (see proposed Sec.
201.409(d)(19)).
t. ``Expiration Date.'' For Type B medicated feeds requiring an
expiration date, in accordance with Sec. 514.1(b)(5)(x), the proposed
rule would require this section of the proprietary Type B medicated
feed label to have the heading ``Expiration Date,'' followed by the
expiration date of the proprietary Type B medicated feed.
Alternatively, the proposed rule would allow for this section of the
proprietary Type B medicated feed label to refer to the location on the
proprietary Type B medicated feed label or immediate container where
the expiration date is printed (see proposed Sec. 201.409(d)(20)).
u. ``Revision Date.'' The proposed rule would require this section
of the proprietary Type B medicated feed label to have the heading
``Revision Date,''
[[Page 18305]]
followed by the date of the most recent revision of the proprietary
Type B medicated feed label, listing the month followed by the year
(see proposed Sec. 201.409(d)(21)). This information is important to
ensure that the most current approved version of the proprietary Type B
medicated feed label is being used.
5. Proprietary Type C Medicated Feed Label (Proposed Sec. 201.409(e))
The proposed rule would establish content and format requirements
for a proprietary Type C medicated feed label for new animal drugs
approved or conditionally approved for use in animal feeds (see
proposed Sec. 201.409(e)). FDA may approve or conditionally approve
applications for proprietary final formulations of Type C medicated
feeds. For some proprietary Type C medicated feeds, the formulation and
labeling are approved in an NADA. In other situations, the underlying
data and labeling for the proprietary Type C medicated feed to support
the approved uses are maintained in a VMF. For example, this would
include situations in which a proprietary Type C medicated feed is
manufactured via modification to an approved formulation published in
the CFR or where a feed manufacturer creates its own proprietary
formulation. The application for a proprietary Type C medicated feed
will include the proprietary label for the final Type C medicated feed.
A proprietary Type C medicated feed label is on the immediate
container, which is typically a bag or bulk container.
The proposed rule would require the following information to be
presented on the proprietary Type C medicated feed label for an
approved or conditionally approved new animal drug and in the following
order (see proposed Sec. 201.409(e)). Unless otherwise indicated, this
information would be the same as that required by proposed Sec.
201.405(a) for full prescribing information for approved or
conditionally approved Rx new animal drugs, proposed Sec. 201.407(a)
for full product information for approved or conditionally approved OTC
new animal drugs, proposed Sec. 201.409(a) for the Type A medicated
article label, or proposed Sec. 201.409(d) for the proprietary Type B
medicated feed label.
a. Proprietary Type C medicated feed identification. The proposed
rule would require this section of the proprietary Type C medicated
feed label to identify the Type C medicated feed (see proposed Sec.
201.409(e)(1)). This section of the proprietary Type C medicated feed
label would be required to include the following components in order:
i. Proprietary name of the Type C medicated feed. The proposed rule
would require this subsection of the proprietary Type C medicated feed
label to include the proprietary name of the Type C medicated feed (see
proposed Sec. 201.409(e)(1)(i)).
ii. Established name of the Type C medicated feed. The proposed
rule would require this subsection of the proprietary Type C medicated
feed label to include the established name of the Type C medicated
feed. The established name of the proprietary Type C medicated feed
would include the active moiety or active ingredient of each new animal
drug, as determined by FDA, followed by an identifying statement of,
``Type C medicated feed,'' ``Type C liquid medicated feed,'' ``Type C
top-dress medicated feed,'' ``Type C free-choice medicated feed,'' or
``Type C liquid free-choice medicated feed,'' as applicable (see
proposed Sec. 201.409(e)(1)(ii)). The identifying statements also
clearly designate the medicated feeds as Type C (as opposed to a Type
B) medicated feeds. The identifying statements also distinguish Type C
liquid medicated feeds from other Type C medicated feeds, which is
important because Type C liquid medicated feeds have unique approval
and labeling requirements (see Sec. 558.5). Similarly, Type C free-
choice medicated feeds have specific requirements for their approval
(see Sec. 510.455).
b. VFD cautionary statement. For VFD new animal drugs, the proposed
rule would require this section of the proprietary Type C medicated
feed label to provide the VFD cautionary statement, in accordance with
Sec. 558.6(a)(6), as described in proposed Sec. 201.409(a)(2) for the
Type A medicated article label (see proposed Sec. 201.409(e)(2)).
c. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the
proprietary Type C medicated feed label to include a conditional
approval statement, as described in proposed Sec. 201.405(a)(3) for
full prescribing information for Rx new animal drugs (see proposed
Sec. 201.409(e)(3)).
d. ``Indications for Use.'' The proposed rule would require this
section of the proprietary Type C medicated feed label to have the
heading ``Indications for Use,'' followed by the approved or
conditionally approved indications(s) and target animal(s), as
described in proposed Sec. 201.407(a)(3) for full product information
for OTC new animal drugs, with the exception of the heading (see
proposed Sec. 201.409(e)(4)).
e. Extralabel use statement. The proposed rule would require this
section of the proprietary Type C medicated feed label to include an
extralabel use statement, as described in proposed Sec. 201.409(a)(6)
for the Type A medicated article label (see proposed Sec.
201.409(e)(5)).
f. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the proprietary Type C medicated
feed label to have the heading ``Active Ingredient,'' or ``Active
Ingredients,'' followed by the established name and approved
concentration of each active ingredient (see proposed Sec.
201.409(e)(6)). If the proprietary Type C medicated feed contains one
active ingredient, the proposed rule would require this section of the
proprietary Type C medicated feed label to be entitled ``Active
Ingredient.'' If the proprietary Type C medicated feed contains more
than one active ingredient, the proposed rule would require this
section of the proprietary Type C medicated feed label to be entitled
``Active Ingredients.'' Because the proprietary Type C medicated feed
label applies to a final Type C medicated feed, a single concentration
would be required for each active ingredient rather than a range.
g. ``Guaranteed Analysis.'' The proposed rule would require this
section of the proprietary Type C medicated feed label to have the
heading ``Guaranteed Analysis,'' followed by the nutritional content
guarantees and other required specifications for the final proprietary
Type C medicated feed, as described in Sec. 201.409(d)(8) for the
proprietary Type B medicated feed label (see proposed Sec.
201.409(e)(7)).
h. ``Ingredients.'' The proposed rule would require this section of
the proprietary Type C medicated label to have the heading
``Ingredients,'' followed by a listing of the feed ingredients in the
proprietary Type C medicated feed, as described in Sec. 201.409(d)(9)
for the proprietary Type B medicated feed label (see proposed Sec.
201.409(e)(8)).
i. ``Feeding Directions.'' The proposed rule would require this
section of the proprietary Type C medicated feed label to have the
heading ``Feeding Directions,'' followed by the approved feeding
directions (see proposed Sec. 201.409(e)(9)).
j. ``Warnings.'' The proposed rule would require this section of
the proprietary Type C medicated feed label to have the heading
``Warnings,''
[[Page 18306]]
followed by the ``Warnings'' section, as described in proposed Sec.
201.409(a)(10) for the Type A medicated article label (see proposed
Sec. 201.409(e)(10)).
k. ``Additional Recommendations.'' For new animal drugs having
precautions, the proposed rule would require this section of the
proprietary Type C medicated feed label to have the heading
``Additional Recommendations,'' followed by all precautions, as
described in proposed Sec. 201.407(a)(8) for full product information
for OTC new animal drugs (see proposed Sec. 201.409(e)(11)).
l. ``Other Effects You May Notice.'' For new animal drugs that have
effects on the target animal(s) that are not considered
contraindications, target animal safety warnings, adverse reactions, or
post-approval adverse drug experiences, and FDA determines that these
effects are required to be described on labeling, the proposed rule
would require this section of the proprietary Type C medicated feed
label to have the heading ``Other Effects You May Notice,'' followed by
a description of the effects. This section of the proprietary Type C
label would be the same as described in proposed Sec. 201.407(a)(9)
for full product information for OTC new animal drugs (see proposed
Sec. 201.409(e)(12)).
m. ``Net Weight.'' The proposed rule would require this section of
the proprietary Type C medicated feed label to have the heading ``Net
Weight,'' followed by the net weight of the Type C medicated feed in
the immediate container (see proposed Sec. 201.409(e)(13)).
n. ``Storage, Handling, and Disposal.'' The proposed rule would
require this section of the proprietary Type C medicated feed label to
have the heading ``Storage, Handling, and Disposal,'' followed by
storage information for the Type C medicated feed, as well as any
required handling, and disposal information, as described in proposed
Sec. 201.405(a)(20) for full prescribing information for Rx new animal
drugs (see proposed Sec. 201.409(e)(14)).
o. ``Questions/Comments?'' The proposed rule would require this
section of the proprietary Type C medicated feed label to have the
heading ``Questions/Comments?,'' followed by the sponsor's contact
information for users of the Type C medicated feed to facilitate
requesting additional information on the product or to report suspected
adverse drug experiences. FDA's contact information for voluntary
reporting of adverse drug experiences for animal drugs would also be
required (see proposed Sec. 201.409(e)(15)).
The sponsor's contact information would be the name of the
manufacturer, packer, or distributor, whichever is identified in the
``Name and place of business'' section of the Type C medicated feed
(see proposed Sec. 201.409(e)(17)). If more than one business is
identified in the ``Name and place of business'' section of the
proprietary Type C medicated feed label, the drug sponsor would select
the most appropriate of these businesses to use in the ``Questions/
Comments?'' section to provide additional information about the Type C
medicated feed and to contact regarding suspected adverse drug
experiences.
The statements in this section of the proprietary Type C medicated
feed label would be required to be structured as follows: ``Contact
[insert name of business] at [insert business telephone number] or
[insert business web address]. To report side effects, contact [insert
name of business] at [insert business telephone number]. For additional
information about reporting side effects or other problems with
medicated feeds, contact FDA at [insert current FDA telephone number
for voluntary reporting of adverse drug experiences] or [insert current
FDA web address for voluntary reporting of adverse drug experiences].''
Sponsors can search FDA's website or contact FDA by telephone to find
the current FDA telephone number or web address for voluntary reporting
of adverse drug experiences for animal drugs.
p. NADA/ANADA approval statement. For approved or generic approved
proprietary Type C medicated feeds, the proposed rule would require
this section of the proprietary Type C medicated feed label to include
an ``NADA approval statement'' or ``ANADA approval statement,''
respectively, as described in proposed Sec. 201.405(a)(21) for full
prescribing information for Rx new animal drugs (see proposed Sec.
201.409(e)(16)).
q. Name and place of business. The proposed rule would require this
section of the proprietary Type C medicated feed label to identify name
and place of business of the manufacturer, packer, or distributor, as
described in proposed Sec. 201.405(a)(22) for full prescribing
information for Rx new animal drugs (see proposed Sec.
201.409(e)(17)).
r. ``Lot, Batch, or Control Number.'' The proposed rule would
require this section of the proprietary Type C medicated feed label to
have the heading ``Lot, Batch, or Control Number,'' followed by the
identifying lot, batch, or control number of the Type C medicated feed.
Alternatively, the proposed rule would allow for this section of the
proprietary Type C medicated feed label to refer to the location on the
proprietary Type C medicated feed label or immediate container where
the lot, batch, or control number is printed (see proposed Sec.
201.409(e)(18)).
s. ``Expiration Date.'' For Type C medicated feeds requiring an
expiration date, in accordance with Sec. 514.1(b)(5)(x), the proposed
rule would require this section of the proprietary Type C medicated
feed label to have the heading ``Expiration Date,'' followed by the
expiration date of the proprietary Type C medicated feed.
Alternatively, the proposed rule would allow for this section of the
proprietary Type C medicated feed label to refer to the location on the
proprietary Type C medicated feed label or immediate container where
the expiration date is printed (see proposed Sec. 201.409(e)(19)).
t. ``Revision Date.'' The proposed rule would require this section
of the proprietary Type C medicated feed label to have the heading
``Revision Date,'' followed by the date of the most recent revision of
the proprietary Type C medicated feed label, listing the month followed
by the year (see proposed Sec. 201.409(e)(20)).
6. Other Approved Labeling for Type A Medicated Articles (Proposed
Sec. 201.409(f))
The proposed rule would establish content and format requirements
for the information presented on other approved labeling for Type A
medicated articles approved or conditionally approved for use in animal
feeds. Other approved labeling for Type A medicated articles includes,
but is not limited to, labeling on shipping cartons containing bags of
Type A medicated articles (see proposed Sec. 201.409(f)).
The proposed rule would require the following information to be
presented on other approved labeling for Type A medicated articles and
in the following order (see proposed Sec. 201.409(f)). Unless
otherwise indicated, this information would be the same as that
required by proposed Sec. 201.405(a) for full prescribing information
for approved or conditionally approved Rx new animal drugs, or proposed
Sec. 201.409(a) for a Type A medicated article label.
a. Type A medicated article identification. The proposed rule would
require this section of the other approved labeling for Type A
medicated articles to include, in order, the proprietary name and the
established
[[Page 18307]]
name of the Type A medicated article (see proposed Sec.
201.409(f)(1)).
b. VFD cautionary statement. For VFD new animal drugs, the proposed
rule would require this section of the other approved labeling for Type
A medicated articles to provide the VFD cautionary statement, in
accordance with Sec. 558.6(a)(6), as described in proposed Sec.
201.409(a)(2) for the Type A medicated article label (see proposed
Sec. 201.409(f)(2)).
c. ``Active Ingredient'' or ``Active Ingredients.'' The proposed
rule would require this section of the other approved labeling for Type
A medicated articles to have the heading ``Active Ingredient'' or
``Active Ingredients,'' followed by the established name and
concentration of each active ingredient in the Type A medicated
article. If the Type A medicated article contains one active
ingredient, the proposed rule would require this section of the other
approved labeling for Type A medicated articles to be entitled ``Active
Ingredient.'' If the Type A medicated article contains more than one
active ingredient, the proposed rule would require this section of the
other approved labeling for Type A medicated articles to be entitled
``Active Ingredients'' (see proposed Sec. 201.409(f)(3)).
d. Conditional approval statement. For conditionally approved new
animal drugs, the proposed rule would require this section of the other
approved labeling for Type A medicated articles to include a
conditional approval statement, as described in proposed Sec.
201.405(a)(3) for full prescribing information for Rx new animal drugs
(see proposed Sec. 201.409(f)(4)).
e. ``Net Contents.'' The proposed rule would require this section
of the other approved labeling for Type A medicated articles to have
the heading ``Net Contents,'' followed by the contents of the container
to which the other approved labeling for Type A medicated articles
applies (see proposed Sec. 201.409(f)(5)).
f. ``Storage and Handling.'' The proposed rule would require this
section of the other approved labeling for Type A medicated articles to
have the heading ``Storage and Handling,'' followed by storage
information for the Type A medicated article (see proposed Sec.
201.409(f)(6)). Also, any handling information required for safe and
effective use of the Type A medicated article would be included in this
section. Information on disposal of the Type A medicated article would
not be required to be included on other approved labeling for Type A
medicated articles.
g. NADA/ANADA approval statement. For approved or generic approved
proprietary Type A medicated articles, the proposed rule would require
this section of the other approved labeling for Type A medicated
articles to include an ``NADA approval statement'' or ``ANADA approval
statement,'' respectively, as described in proposed Sec.
201.405(a)(21) for full prescribing information for Rx new animal drugs
(see proposed Sec. 201.409(f)(7)).
h. Name and place of business. The proposed rule would require this
section of the other approved labeling for Type A medicated articles to
identify name and place of business of the manufacturer, packer, or
distributor, as described in proposed Sec. 201.405(a)(22) for full
prescribing information for Rx new animal drugs (see proposed Sec.
201.409(f)(8)).
i. ``Lot Number and Expiration Date.'' The proposed rule would
require this section of the other approved labeling for Type A
medicated articles to have the heading ``Lot Number and Expiration
Date,'' followed by the identifying lot or control number(s) and the
expiration date(s) of the Type A medicated article within the container
(see proposed Sec. 201.409(f)(9)). The container may include more than
one lot of the Type A medicated article, and therefore, more than one
lot or control number and expiration date may be listed in this section
of other approved labeling for Type A medicated articles.
j. ``Revision Date.'' The proposed rule would require this section
of the other approved labeling for Type A medicated articles to have
the heading ``Revision Date,'' followed by the date of the most recent
revision of the other approved labeling for Type A medicated articles,
listing the month followed by the year (see proposed Sec.
201.409(f)(10)).
G. Exemptions From Labeling Requirements for Approved or Conditionally
Approved New Animal Drugs (Proposed Sec. 201.411)
FDA would provide sponsors the opportunity to request an exemption
from one or more specific requirements set forth in this proposed
subpart on the basis that the requirements are not appropriate for the
specific approved or conditionally approved new animal drug (see
proposed Sec. 201.411).
An exemption request would be required to be submitted to the
corresponding application or investigational new animal drug file
(INAD) for the new animal drug. A separate request would be required to
be submitted for each new animal drug for which an exemption is sought.
Requests for exemptions would be granted or denied by the Director of
FDA's Center for Veterinary Medicine or the Director's designee (see
proposed Sec. 201.411(a)). The sponsor seeking an exemption would be
required to: (1) describe why the particular requirement for which the
exemption is requested was not appropriate for the new animal drug; (2)
describe why granting the exemption would not adversely impact the
safety or effectiveness of the use of the new animal drugs; and (3)
include copies of all draft labeling proposed to be used for the new
animal drug (see proposed Sec. 201.411(b)). We anticipate that such
exemptions would be rare.
H. Labeling Requirements for Certain Approved or Conditionally Approved
New Animal Drugs (Proposed Sec. 201.413)
This section of the proposed regulations would consolidate, and
where appropriate, update existing labeling requirements pertaining to
certain approved or conditionally approved new animal drugs that would
continue to apply in addition to the other labeling requirements in
proposed subpart H. Currently, the labeling requirements for these new
animal drugs are dispersed throughout the regulations. It would be
helpful to new animal drug sponsors and FDA reviewers if the proposed
rule were to consolidate, and where appropriate, update the additional
labeling requirements for these specific new animal drugs in the same
subpart of the CFR as general labeling requirements for approved or
conditionally approved new animal drugs.
This section also proposes a new labeling provision for all new
animal drugs approved or conditionally approved for use in horses and
anthelmintic new animal drugs for certain species of animals.
We may propose to amend Sec. 201.413 in the future to include
additional labeling requirements for certain specific new animal drugs
as appropriate.
1. Approved or Conditionally Approved Corticosteroid-Containing New
Animal Drugs for Oral, Injectable, and/or Ophthalmic Use
The proposed rule would move labeling requirements currently
provided in Sec. 510.410 relating to corticosteroid-containing new
animal drugs intended for oral, injectable, and/or ophthalmic use to
proposed Sec. 201.413(a). We also propose a conforming amendment to
remove current Sec. 510.410.
Section 510.410 was originally issued by FDA in 1970 as Sec.
135.101 (35 FR 11556, July 18, 1970) and provided
[[Page 18308]]
background information and established certain labeling requirements
for corticosteroid animal drugs administered orally or parenterally.
The regulation stated that such corticosteroid animal drugs must bear
the veterinary prescription legend and meet the labeling requirements
in Sec. 201.105 for prescription new animal drugs. The regulation also
required the labeling of these products to bear a warning statement
regarding potential adverse reproductive effects to the treated animals
when these drugs are administered during the last trimester of
pregnancy, specifically premature parturition followed by dystocia,
fetal death, retained placenta, and metritis. The regulation was
subsequently revised in 1972 (37 FR 24343, November 16, 1972) to
address corticosteroid animal drugs for oral, injectable, and
intramammary use. In 1984, FDA amended the regulation on labeling
requirements for use of corticosteroid animal drugs again to add
ophthalmic products, delete intramammary products, and to include an
additional warning concerning certain potential congenital/teratogenic
effects (49 FR 48535, December 13, 1984). Ophthalmic products were
added to the regulation based on the results of a published study
supporting the need for these warning statements for ophthalmic use
corticosteroid drugs. Intramammary corticosteroid animal drugs were
removed from the regulation because intramammary products no longer
included steroids in their formulations.
The proposed rule would redesignate Sec. 510.410 as proposed Sec.
201.413(a) and revise its contents to remove some of the background
information because we believe it is now well understood. Furthermore,
we propose to update some of the warning statements to use more concise
language. These animal drug products would continue to be subject to
the labeling requirements for prescription new animal drugs. However,
because the labeling requirements for approved or conditionally
approved prescription new animal drugs would no longer be in Sec.
201.105, we would update the citation to refer to the labeling
requirements for prescription new animal drugs in proposed subpart H.
The proposed rule would require the warning statements for adverse
reproductive effects to be included in the ``Animal Safety Warnings and
Precautions'' subsection of labeling for approved or conditionally
approved corticosteroid new animal drugs for oral, and/or injectable
use (see proposed Sec. 201.413(a)). For corticosteroid new animal
drugs approved or conditionally approved for ophthalmic use, per this
proposal, we may require these statements to also be included in the
``Animal Safety Warnings and Precautions'' subsection of labeling. For
example, the warning statements might not be necessary for ophthalmic
corticosteroid new animal drugs if data are provided to us that
demonstrate the intended use is not associated with adverse
reproductive effects in the treated animal.
2. Anthelmintic New Animal Drugs
The proposed rule would move labeling requirements currently
provided in Sec. 500.25 for approved or conditionally approved OTC
anthelmintic new animal drugs to proposed Sec. 201.413(b)(1). Labeling
requirements currently provided in Sec. 500.25 for OTC anthelmintic
new animal drugs that are indexed would be moved to Sec. 516.155 (21
CFR 516.155), ``Labeling of indexed drugs''. We also propose a
conforming amendment to remove current Sec. 500.25. Furthermore, the
proposed rule would require that all approved or conditionally approved
anthelmintic new animal drugs for use in sheep, goats, cattle, horses,
swine, and/or poultry include statements on labeling on appropriate use
of these drugs to minimize anthelmintic resistance development (see
proposed Sec. 201.413(b)(2)).
Section 500.25 was originally issued by FDA in 1974 as Sec.
135.111 (39 FR 7165 at 7166, February 25, 1974) and required that
labeling for anthelmintic animal drugs not carrying the prescription
statement bear the following statement ``Consult your veterinarian for
assistance in the diagnosis, treatment, and control of parasitism.''
Labeling of approved anthelmintic animal drugs not carrying the
prescription statement were to be revised accordingly by February 25,
1975, and labeling of all subsequently approved non-prescription
anthelmintic new animal drugs were to bear the statement. In 2007,
Sec. 500.25 was amended to add the labeling requirement for indexed
non-prescription anthelmintic new animal drugs (72 FR 69108 at 69120,
December 6, 2007).
The proposed rule would redesignate portions of Sec. 500.25 for
approved or conditionally approved OTC anthelmintic new animal drugs,
including OTC anthelmintic new animal drugs for use in animal feeds, as
proposed Sec. 201.413(b)(1) and update some of its contents. VFD
anthelmintic new animal drugs for use in or on animal feeds would be
excluded from this requirement. The labeling statement would be
required to be placed in the ``Additional Recommendations'' section of
labeling. Reference to being able to revise labeling without prior
approval would be removed because the labeling statement would be
required for approval or conditional approval. Reference to an
effective date of February 25, 1975 would be removed.
Portions of Sec. 500.25 for indexed OTC anthelmintic new animal
drugs would be redesignated as paragraph (c) in Sec. 516.155,
``Labeling of indexed drugs''. Reference to an effective date of
February 25, 1975 would be removed. The current Sec. 516.155(c) would
be redesignated as Sec. 516.155(d).
The proposed rule would also require all approved or conditionally
approved anthelmintic new animal drugs for use in sheep, goats, cattle,
horses, swine, and/or poultry to include statements on their labeling
providing information to end users on appropriate use of these drugs to
minimize anthelmintic resistance development. FDA's Center for
Veterinary Medicine held a public meeting on antiparasitic drug use and
resistance in ruminants and equines on March 5 and 6, 2012. During that
meeting, a panel of veterinary parasitology experts discussed the
emerging problem of anthelmintic resistance cattle, horses, and
especially small ruminants in the United States, contributing factors
to resistance development, strategies to detect and manage anthelmintic
resistance, and the importance of educating both veterinarians and
other end users about how to detect and manage anthelmintic resistance.
Since this meeting, published reports in the United States continue to
support that anthelmintic resistance is spreading and is particularly
concerning in grazing species (cattle, sheep, goats, and horses), but
is also becoming a problem in swine and poultry.
It is in the interest of animal health to take a proactive approach
to ensure that anthelmintics are used appropriately to help maintain
the effectiveness of these drugs. Therefore, the proposed rule would
require that all approved or conditionally approved anthelmintic new
animal drugs for use in sheep, goats, cattle, horses, swine, and/or
poultry include statements on their labeling providing information to
end users on appropriate use of these drugs to minimize antiparasitic
resistance development. These statements would include information on
appropriate dosing, anthelmintic drug selection, effectiveness
monitoring, the integration of anthelmintic drug use with other
parasite management practices, and other information as needed (see
[[Page 18309]]
proposed Sec. 201.413(b)(2)). The statements would be required in the
``Other Warnings'' subsection of labeling, and if applicable,
additional statements may be required in the ``Dosage and
Administration'' section of labeling for Rx anthelmintic new animal
drugs, the ``Directions'' section of labeling for OTC anthelmintic new
animal drugs, or the ``Feeding Directions'' section or subsection of
labeling for anthelmintic new animal drugs for use in animal feeds. We
would determine specific statements during review of the new animal
drug and its labeling as part of the approval process and/or via
guidance developed by FDA.
3. Approved or Conditionally Approved New Animal Drugs for Use in
Horses
The proposed rule would require that all approved or conditionally
approved new animal drugs for use in horses include in the ``Other
Warnings'' subsection of labeling a statement advising against the use
of the drug in certain horses (see proposed Sec. 201.413(c)).
Historically, drugs approved or conditionally approved for use in
horses do not have tolerance levels established because FDA does not
consider horses to be food-producing animals. Therefore, FDA currently
does not require a human food safety evaluation of new animal drugs
intended for use in horses. Because there is no human food safety
evaluation of the new animal drug, FDA does not have the data needed to
ensure that horses that have been treated with the drugs could safely
be used for human consumption and sponsors may not label their drugs as
appropriate for use in horses intended for use as human food. Proposed
Sec. 201.413(c) would require that all new animal drugs approved or
conditionally approved for use in horses include a statement in the
``Other Warnings'' subsection of labeling advising against use of the
drug in horses intended for human consumption.
I. Proposed Conforming Amendments
We also propose to amend the following sections:
Sec. 201.15 pertaining to foreign translations of
labeling,
Sec. 201.100 pertaining to prescription drugs for human
use,
Sec. 201.105 pertaining to prescription drugs for animal
use,
part 501 pertaining to animal food labeling,
Sec. 514.1 pertaining to new animal drug applications,
and
Sec. 516.155 pertaining to labeling of indexed drugs.
Also, we propose to remove the following sections and incorporate
their requirements in proposed new subpart H:
Sec. 500.25 pertaining to OTC anthelmintic drug use in
animals, and
Sec. 510.410 pertaining to corticosteroids for oral,
injectable, and ophthalmic use in animals.
We propose to remove the following sections:
Sec. 500.55 pertaining to the exemption of certain drug-
labeling requirements, and
Sec. Sec. 510.105 and 510.106 pertaining to labeling of
drugs for use in milk-producing animals.
The proposed rule would establish translation requirements for
approved or conditionally approved new animal drug labeling that
contains any representation of a foreign language in proposed Sec.
201.404(i) and (j). Therefore, we propose a change to Sec. 201.15,
``Drugs; prominence of required label statements.'' We propose adding
paragraph (4) to Sec. 201.15(c). Proposed paragraph (c)(4) would
exempt approved or conditionally approved new animal drugs from the
requirements established in Sec. 201.15(c) and state that foreign
translations of the labeling for approved or conditionally approved new
animal drugs must comply with Sec. 201.404(i) and (j).
The proposed rule would amend Sec. 201.100, ``Prescription drugs
for human use,'' in paragraph (d) to remove the words, ``and Sec.
201.105(b)(2)'' from the introductory text. This conforming amendment
would be in conjunction with conforming amendments proposed for Sec.
201.105, ``Veterinary drugs'' (see discussion below), which includes
the removal of Sec. 201.105(f). Paragraph (f) provides labeling
requirements for prescription drugs intended for both human and
veterinary use.
Current Sec. 201.105, entitled ``Veterinary drugs,'' provides
requirements, including labeling requirements, for drugs subject to
section 503(f)(1) of the FD&C Act, which are prescription drugs for
animal use. These drugs include approved or conditionally approved
prescription new animal drugs, prescription new animal drugs listed in
the index of legally marketed unapproved new animal drugs for minor
species, and prescription animal drugs not subject to an approved or
conditionally approved application or index listing. Section 201.100,
``Prescription drugs for human use,'' serves a similar purpose for
prescription human drugs. The proposed rule would revise the title of
Sec. 201.105 to read ``Prescription drugs for animal use.'' This would
clarify the scope of the section and be consistent with the title of
its counterpart for human prescription drugs in Sec. 201.100.
We propose minor editorial changes to update Sec. 201.105(a),
which provides requirements, other than labeling requirements, for
prescription animal drugs.
To accommodate the proposed content and format requirements in
proposed subpart H for labeling authorized in approved or conditionally
approved new animal drug applications, the proposed rule would change
Sec. 201.105 to provide the labeling requirements for approved or
conditionally approved prescription new animal drugs separately from
the labeling requirements for prescription new animal drugs listed in
the index of legally marketed unapproved new animal drugs for minor
species, and prescription animal drugs not subject to an approved or
conditionally approved application or index listing. Accordingly, we
propose to insert a new paragraph Sec. 201.105(b) that would provide
labeling requirements for prescription new animal drugs approved under
section 512 of the FD&C Act or conditionally approved under section 571
of the FD&C Act. The provisions in the proposed paragraph Sec.
201.105(c) would apply to prescription new animal drugs listed in the
index of legally marketed unapproved new animal drugs for minor species
established under section 572 of the FD&C Act, and prescription animal
drugs not subject to an approved or conditionally approved application
or index listing.
The proposed rule would provide requirements for the labeling
components for approved or conditionally approved prescription new
animal drugs identified in proposed Sec. 201.405 (see proposed Sec.
201.105(b)(1)), which include labeling providing full prescribing
information, labels, small labels, labeling for secondary containers
that include a package insert, shipping labeling, and other approved
labeling for prescription new animal drugs. Such labeling would be
required to contain adequate information for use of the drug, including
indications for use, dosages, routes of administration, frequency and
duration of administration, and any relevant contraindications,
warnings, precautions, and adverse reactions, under which veterinarians
licensed by law to administer the drug can use the drug safely and for
the purposes for which it is intended, including all purposes for which
it is advertised or represented (see proposed Sec. 201.105(b)(1)(i)).
The labeling
[[Page 18310]]
components identified in proposed Sec. 201.405 also would be required
to be the labeling authorized by the approved new animal drug
application or conditionally approved new animal drug application for
the prescription new animal drug (see proposed Sec.
201.105(b)(1)(ii)).
These requirements for the labeling components identified in
proposed Sec. 201.405 would be consistent with requirements in current
paragraph Sec. 201.105(c) for labeling on or within the package from
which the approved or conditionally approved prescription new animal
drugs is dispensed. We also propose editorial revisions to use more
current terminology regarding the types of information required to
provide adequate information for use of the drug by veterinarians.
These labeling components also would be required to comply with the
applicable content and format requirements of proposed subpart H (see
proposed Sec. 201.105(b)(1)(iii)).
The exemption currently provided in Sec. 201.105(c)(2) permits,
upon written request to the Commissioner of Food and Drugs, the
labeling information required by Sec. 201.105(c)(1) (i.e., adequate
information for use) to be omitted from the dispensing container of
prescription animal drugs for which the directions, hazards, warnings,
and use information are commonly known to licensed veterinarians.
Providing an exemption from the requirement that all prescription
animal drugs must provide labeling that bears adequate information for
use by veterinarians does not ensure safe and effective use of these
drugs and is no longer warranted. Additional risks relating to the use
of an animal drug may become known long after the drug is first
marketed, even when veterinarians have become familiar with the
directions, hazards, and warnings concerning its use. Moreover, in some
cases, labeling may need to be revised to include additional safety
information. Therefore, the proposed rule would revoke the exemption
provided in current Sec. 201.105(c)(2). As discussed below, we also
propose to remove Sec. 500.55, which lists the animal drugs to which
this exemption has been applied.
The proposed rule would set forth requirements for any labeling, as
defined in section 201(m) of the FD&C Act, for approved or
conditionally approved prescription new animal drugs, distributed by or
on behalf of the manufacturer, packer, or distributor of the drug, that
provides or purports to provide information for use or prescribes,
recommends, or suggests a dosage for use of the drug (see proposed
Sec. 201.105(b)(2)), consistent with the requirements in current Sec.
201.105(d) for such prescription new animal drugs. Labeling, as defined
in section 201(m) of the FD&C Act, means ``all labels and other
written, printed, or graphic matter (1) upon any article or any of its
containers or wrappers, or (2) accompanying such article.'' Thus,
labeling includes material such as promotional labeling, in addition to
the labeling authorized in the approved new animal drug application or
the conditionally approved new animal drug application. Such labeling
that provides or purports to provide information or a dosage for the
drug's use would be required to contain adequate information to ensure
licensed veterinarians can use the drug safely and for the purposes for
which the drug is intended, including all conditions for which the drug
is advertised or represented. For the labeling of the approved or
conditionally approved prescription animal drug to contain adequate
information for use by veterinarians, proposed Sec. 201.105(b)(2)
would require such labeling to include the indications for use,
dosages, routes of administration, frequency and duration of
administration, and any relevant contraindications, warnings,
precautions, and adverse reactions, and information relevant to
compliance with the new animal drug provisions of the FD&C Act. It
would also require the labeling components providing such information
for use to be the same in language and emphasis as the labeling
authorized by the approved or conditionally approved new animal drug
application, and any other labeling components would have to be
consistent with and not contrary to such authorized labeling (see
proposed Sec. 201.105(b)(2)(i)). The labeling would be required to
contain the same information concerning the ingredients of the drug as
appears on the labeling authorized by the approved new animal drug
application or the conditionally approved new animal drug application
(see proposed Sec. 201.105(b)(2)(ii)).
We propose requirements for the label of prescription new animal
drugs listed in the index of legally marketed unapproved new animal
drugs for minor species established under section 572 of the FD&C Act,
and prescription animal drugs not subject to an approved or
conditionally approved application or index listing, that are
consistent with those currently provided in Sec. 201.105(b) (see
proposed Sec. 201.105(c)(1)). The proposed rule includes requirements
for the labeling on or within the package from which such drugs are to
be dispensed that are consistent with the requirements currently
provided in Sec. 201.105(c) (see proposed Sec. 201.105(c)(2)). In
addition, the proposed rule includes editorial revisions to use more
current terminology to identify the types of information that would
need to be included on the labeling on or within the dispensing
container in order to provide adequate information for use of such
drugs by veterinarians (see proposed Sec. 201.105(c)(2)). The proposed
rule would revoke the exemption provided in current Sec. 201.105(c)(2)
for the reasons described previously.
Proposed Sec. 201.105(c)(3) would require that any labeling, as
defined in section 201(m) of the FD&C Act, for prescription new animal
drugs listed in the index of legally marketed unapproved new animal
drugs for minor species, or prescription animal drugs not subject to an
approved or conditionally approved application or an index listing,
that is distributed by or on behalf of the manufacturer, packer, or
distributor of the drug, that provides information for use or a dosage
for use of the drug contain adequate information for use of the drug by
licensed veterinarians. This provision is consistent with the
requirements currently provided in Sec. 201.105(d) for these
prescription animal drugs. In addition, all labeling for such
prescription animal drugs, except labels and cartons, that contain
information for use of the drug would be required to include the date
of the issuance or latest revision of such labeling, consistent with
the requirements currently provided in Sec. 201.105(e) (see proposed
Sec. 201.105(c)(4)).
The proposed rule would replace the current proviso language in
Sec. 201.105(d)(2) relating to prescription animal drug reminder-piece
labeling with a provision that is similar to the reminder labeling
provision at Sec. 201.100(f) (21 CFR 201.100(f)) for human
prescription drugs (see proposed Sec. 201.105(d)). Specifically, the
proposed provision would replace the term reminder-piece labeling with
the term reminder labeling and define reminder labeling for
prescription animal drugs in a manner similar to how that term is
defined for prescription human drugs. In the past, we have relied on
the definition for reminder labeling in Sec. 201.100(f) as a guide
when reviewing such labeling because the current proviso language in
Sec. 201.105 lacks such a detailed definition. We propose to modify
the definition for reminder labeling found at Sec. 201.100(f) to
establish a similar definition for prescription animal drugs. The
proposed use of the term reminder
[[Page 18311]]
labeling for prescription animal drugs and the proposed inclusion of a
definition for this term that is similar to the definition in Sec.
201.100(f) is clearer and more accurate than the current definition for
reminder-piece labeling (see proposed Sec. 201.105(d)).
Current Sec. 201.105(f) provides labeling requirements for
prescription drugs intended for both human and veterinary use. The
proposed rule would remove this provision, which was established in
1960 (as Sec. 1.106(c)(6)); 25 FR 12592) and is now obsolete. In 1968,
section 512 of the FD&C Act established separate approval requirements
for new animal drugs, including their labeling.
The proposed rule would remove Sec. 500.25, which contains
labeling requirements for OTC anthelmintic new animal drugs. The
requirements for the labeling of approved or conditionally approved OTC
anthelminthic new animal drugs contained in current Sec. 500.25 would
be moved to proposed Sec. 201.413(b)(1), ``Labeling requirements for
certain approved or conditionally approved new animal drugs.'' This
would further consolidate regulations pertaining to labeling of
approved or conditionally approved new animal drugs. The requirements
for the labeling of indexed OTC anthelminthic new animal drugs
contained in current Sec. 500.25 would be moved to Sec. 516.155,
``Labeling of indexed drugs.''
To ensure the safe and effective use of new animal drugs, the
proposed rule would remove from the provision found at Sec. 500.55,
``Exemption from certain drug-labeling requirements,'' and proviso
language at Sec. 201.105(c)(2) that permits animal drug sponsors to
receive an exemption from including certain labeling information
required by Sec. 201.105(c)(1) on the dispensing package for their
products where the Commissioner of Food and Drugs has determined that
such information is already commonly known to veterinarians. Under
Sec. 201.105(c)(1) of this Agency's regulations, the labeling on or
within the dispensing package of prescription new animal drugs must
have adequate information for its use, including indications, effects,
dosages, routes, methods, and frequency and duration of administration,
and any relevant hazards, contraindications, side effects, and
precautions, under which veterinarians licensed by law to administer
the drug can use it safely and for the purposes for which the drug is
intended, including all purposes for which the drug is advertised or
represented. Section 201.105(c)(2) contains certain proviso language
that permits the ``full disclosure'' labeling required by Sec.
201.105(c)(1) to be omitted from the dispensing package of prescription
new animal drugs if the directions, hazards, warnings, and use
information are commonly known to veterinarians. The Commissioner of
Food and Drugs has, upon written request, offered an opinion that such
information may be omitted from the dispensing package for the
prescription animal drugs listed in Sec. 500.55. Only eight animal
drugs have received such an exemption from providing the full
disclosure labeling information otherwise required by Sec.
201.105(c)(1).
The list of unapproved prescription animal drugs currently in Sec.
500.55 that have received an exemption from providing full disclosure
labeling meeting the requirements of Sec. 201.105(c)(1) on their
dispensing package was initially created in 1962. This list was added
to a then-existing provision at 21 CFR 3.515 that permitted full
disclosure labeling to be omitted from the dispensing package of
certain prescription drugs for human use in cases where the
Commissioner of Food and Drugs determined that directions, hazards,
warnings, and use information for such drugs was commonly known to
physicians (27 FR 5428, June 8, 1962). In 1971, when FDA issued
regulations implementing the Animal Drug Amendments of 1968, the human
and animal drug provisions were recodified in separate sections of
FDA's regulations. As a result, the list of animal drugs exempt from
the requirement to have full disclosure labeling on their dispensing
package was moved to Sec. 135.107 and the list of human prescription
drugs exempt from similar labeling requirements was moved to Sec.
201.160. In the mid-1970s, as part of the Agency's reorganization of
its regulations, the animal drug list was moved again to Sec. 500.55.
In 1979, FDA removed Sec. 201.160, the human drug provision
similar to Sec. 500.55, because the Agency's experience had shown that
risks from the use of a drug may be uncovered long after the drug is
first marketed, even for long-used drugs for which physicians had
become familiar with the directions, hazards, and warnings concerning
their use. FDA concluded that current full disclosure labeling should
be provided for all human prescription drugs to ensure that physicians
have the information they need to use these drugs safely. For similar
reasons, full disclosure labeling is needed for all prescription new
animal drugs to ensure veterinarians are able to use these products
safely and effectively. In addition, none of the eight products listed
in Sec. 500.55 received FDA approval for the uses in animals for which
they were generally employed by veterinarians at the time the list of
exempt drugs was initially established in 1962, and several are no
longer used in veterinary medicine. Therefore, we propose to remove
Sec. 500.55 and the proviso language at Sec. 201.105(c)(2).
In part 501 subpart A, we propose to add a new section, Sec.
501.19, ``Animal food; labeling of animal food containing new animal
drugs.'' Proposed Sec. 501.19 would require labeling of animal food
containing an approved or conditionally approved new animal drug to
comply with proposed Sec. 201.409. The requirements in part 501 would
apply only as specified in proposed Sec. 201.409.
The proposed rule would remove Sec. 510.105, ``Labeling of drugs
for use in milk-producing animals'', and Sec. 510.106, ``Labeling of
antibiotic and antibiotic-containing drugs intended for use in milk-
producing animals'', which provide statements required to appear on the
labeling of such drugs for use in milk-producing animals. The
requirements in proposed Sec. Sec. 201.405(a)(10)(i),
201.407(a)(7)(i), and 201.409(a)(10)(i) would supersede the
requirements in Sec. Sec. 510.105 and 510.106.
Section 510.105 was originally issued by FDA in 1960 as 21 CFR 3.18
(25 FR 8321, August 31, 1960) and was recodified as Sec. 135.103 (21
CFR 135.103) in 1971 (36 FR 18375 at 18393, September 14, 1971). In
1975 Sec. 135.103 was redesignated as Sec. 510.105 (40 FR 13802,
March 27, 1975).
Section 510.106 was originally issued by FDA in 1960 as Sec.
146.14 (21 CFR 146.14) (25 FR 8321 at 8322, August 31, 1960). In 1964,
Sec. 146.14 was redesignated as Sec. 148.5 (21 CFR 148.5) (29 FR
15672, November 21, 1964) and subsequently amended in 1965 (30 FR 7040
at 7041, May 26, 1965) to update the warning statements. In 1975 Sec.
148.5 was redesignated as Sec. 510.106 (40 FR 13802, March 27, 1975).
Both Sec. Sec. 510.105 and 510.106 were amended in 1998 to update
the warning statements in those provisions to reflect current practices
in the dairy industry (63 FR 32978, June 17, 1998).
The proposed rule would remove Sec. Sec. 510.105 and 510.106
because the labeling requirements proposed for the subsection entitled
``Withdrawal Periods and Residue Warnings'' or ``Withdrawal Periods''
would supersede such requirements in Sec. Sec. 510.105 and 510.106.
The labeling requirements for the proposed ``Withdrawal Periods and
Residue Warnings'' or ``Withdrawal Periods'' subsection would provide
flexibility to have more targeted and informative statements with
respect to human food safety warnings, including
[[Page 18312]]
milk discard times, withdrawal periods, and residue warning statements
for the labeling of all new animal drugs intended for use in food-
producing animals (see proposed Sec. Sec. 201.405(a)(10)(i),
201.407(a)(7)(i), and 201.409(a)(10)(i)).
The proposed rule would remove Sec. 510.410. The requirements in
current Sec. 510.410 would be moved to proposed Sec. 201.413,
``Labeling requirements for certain approved or conditionally approved
new animal drugs.'' The warning language would be clarified and updated
in proposed Sec. 201.413(a). This would further consolidate
regulations pertaining to labeling of approved or conditionally
approved new animal drugs.
The proposed rule would amend Sec. 514.1, which describes the
requirements for applications for new animal drugs. Current Sec.
514.1(b)(3) describes the labeling that must be included in a new
animal drug application. Paragraphs (ii) through (vi) of current Sec.
514.1(b)(3) describe the labeling required in a new animal drug
application for prescription and nonprescription new animal drugs and
new animal drugs intended for use in the manufacture of medicated
feeds.
The proposed rule would insert a paragraph after Sec.
514.1(b)(3)(i) to indicate that the content and format of all proposed
labeling must comply with subpart H of part 201 of this chapter.
Paragraphs (ii) through (vi) of Sec. 514.1(b)(3) would be
redesignated as paragraphs (iii) through (vii). The current text
``prescription veterinary drugs'' in redesignated paragraphs (iv) and
(vii) would be changed to ``prescription new animal drugs'' to be
consistent with the text used in proposed subpart H.
VI. Proposed Effective/Compliance Dates
If finalized, sponsors of new animal drugs would need to comply
with these proposed regulations within 6 years of the effective date of
the final rule, according to the compliance schedule provided in the
General Requirements section of this proposed rule, discussed in
section V.C. The compliance schedule is based on application number,
with approved NADAs with higher application numbers having the earliest
compliance date because they are more recently approved and therefore
likely to need the fewest labeling revisions. The 6-year compliance
period would begin on the effective date of the final rule (see
proposed Sec. 201.404(a)(4)).
VII. Preliminary Economic Analysis of Impacts
We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, Executive Order 14094, the
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4).
Executive Orders 12866, 13563, and 14094 direct us to assess all
benefits, costs, and transfers of available regulatory alternatives
and, when regulation is necessary, to select regulatory approaches that
maximize net benefits (including potential economic, environmental,
public health and safety, and other advantages; distributive impacts;
and equity). Rules are ``significant'' under Executive Order 12866
Section 3(f)(1) (as amended by Executive Order 14094) if they ``have an
annual effect on the economy of $200 million or more (adjusted every 3
years by the Administrator of [the Office of Information and Regulatory
Affairs (OIRA)] for changes in gross domestic product); or adversely
affect in a material way the economy, a sector of the economy,
productivity, competition, jobs, the environment, public health or
safety, or State, local, territorial, or tribal governments or
communities.'' OIRA has determined that this proposed rule is not a
significant regulatory action as defined by Executive Order 12866
Section 3(f)(1).
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because net annualized compliance costs of the proposed rule
are less than 2 percent of average annual revenues for the smallest
firms in the industry, we propose to certify that the proposed rule
will not have a significant economic impact on a substantial number of
small entities.
The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated impacts, before proposing ``any rule that includes any
Federal mandate that may result in the expenditure by State, local, and
tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation) in any one
year.'' The current threshold after adjustment for inflation is $177
million, using the most current (2022) Implicit Price Deflator for the
Gross Domestic Product. This proposed rule would not result in an
expenditure in any year that meets or exceeds this amount.
The proposed rule, if finalized, would require that sponsors follow
specific content and format requirements for labeling of approved or
conditionally approved new animal drugs. A comprehensive set of
standardized requirements for the content and format of information on
labeling of such drugs currently does not exist. Veterinarians, pet
owners, livestock owners, and other users of new animal drugs may more
easily locate the information they need with standardized labeling.
We quantify potential cost savings to industry and FDA from a
reduction in the quantity and time burden of new animal drug labeling
amendments and informal communications related to new animal drug
labeling. There may be additional benefits to users of approved or
conditionally approved new animal drugs from greater predictability and
ease of reading new animal drug labeling in the form of time saved
searching for content, which we are unable to quantify. Additionally,
animal or human health benefits may result from reductions in
medication errors or improvements in adverse event reporting, which we
cannot quantify.
We expect that new animal drug sponsors would incur one-time costs
to read and understand the rule, revise standard operating procedures
(SOPs) related to labeling, and train employees on the revised SOPs.
New animal drug sponsors would also bear costs to update labeling and
prepare supplemental labeling applications to conform to the proposed
requirements. FDA would incur costs to review these supplemental
applications.
We summarize the quantified benefits and costs in table 2. We
estimate that the annualized benefits over 10 years would range from
$0.143 million to $0.243 million at a 2 percent discount rate, with a
primary estimate of $0.193 million. The annualized costs would range
from $2.16 million to $2.77 million at a 2 percent discount rate, with
a primary estimate of $2.45 million.
The present value of total benefits over 10 years would range from
$1.31 million to $2.23 million at a 2 percent discount rate, with a
primary estimate of $1.77 million. At a 2 percent discount rate, the
present value of total costs would range from $19.78 million to $25.38
million, with a primary estimate of $22.48 million.
[[Page 18313]]
Table 2--Summary of Benefits, Costs, and Distributional Effects of the Proposed Rule
[Millions of 2022 dollars]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Notes (e.g., Risk assumptions; source
Primary Low High Dollar Discount Time citations; whether inclusion of capital
Category estimate estimate estimate year rate horizon effects differs across low, primary,
high estimates; etc.)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
Annualized monetized benefits..... $0.193 $0.143 $0.243 2022 2 10 Cost savings to industry and FDA.
Annualized quantified, but non- .......... .......... .......... .......... .......... .......... ........................................
monetized, benefits.
-----------------------------------------------------------------------------------------------------------------
Unquantified benefits............. Information search cost savings to users of new animal drugs and ........................................
potential benefits to animal or human health.
-----------------------------------------------------------------------------------------------------------------
COSTS:
Annualized monetized costs........ 2.45 2.16 2.77 2022 2 10 ........................................
Annualized quantified, but non- .......... .......... .......... .......... .......... .......... ........................................
monetized, costs.
Unquantified costs................ .......... .......... .......... .......... .......... .......... ........................................
Transfers:
Annualized monetized Federal .......... .......... .......... .......... .......... .......... ........................................
budgetary transfers.
Bearers of transfer gain and loss? .......... .......... .......... .......... .......... .......... ........................................
Other annualized monetized .......... .......... .......... .......... .......... .......... ........................................
transfers.
Bearers of transfer gain and loss? .......... .......... .......... .......... .......... .......... ........................................
Net Benefits:
Annualized monetized net benefits. -2.26 -2.02 -2.53 2022 2 10 ........................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
Category Effects
Notes
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects on State, local, or Tribal None.
governments.
Effects on small businesses........... Quantified effects of less than 2
percent of average annual revenues
for the smallest firms.
Effects on wages...................... None.
Effects on growth..................... None.
--------------------------------------------------------------------------------------------------------------------------------------------------------
We have developed a comprehensive Preliminary Economic Analysis of
Impacts that assesses the impacts of the proposed rule. The full
preliminary analysis of economic impacts is available in the docket for
this proposed rule (Ref. 2) and at https://www.fda.gov/about-fda/economics-staff/regulatory-impact-analyses-ria.
VIII. Analysis of Environmental Impact
The Agency has determined under Sec. 25.30(k) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
IX. Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by the OMB under the Paperwork Reduction Act of
1995 (44 U.S.C. 3501-3521). A description of these provisions is given
in the Description section of this document with an estimate of the
annual reporting burden. Included in the estimate is the time for
reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing each
collection of information.
FDA invites comments on these topics: (1) whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Title: Reporting Associated With New Animal Drug Applications and
Veterinary Master Files; OMB control number 0910-0032--Revision.
Description: The proposed rule, if finalized, would revise the
existing requirements for the content and format of labeling for
approved or conditionally approved new animal drugs that sponsors
submit as part of NADAs or CNADAs, respectively. The proposed rule
would also place labeling requirements that are specific to approved or
conditionally approved new animal drugs in a single location in the
CFR. The proposed rule would apply to the labeling of both Rx and OTC
new animal drugs, as well as new animal drugs for use in animal feeds.
The proposed regulations would provide the following for the
content and format elements of labeling for approved or conditionally
approved new animal drugs:
Description of Respondents: Respondents include persons developing,
manufacturing, and/or researching new animal drugs, commonly referred
to as new animal drug sponsors.
We estimate the burden of the information collection as follows:
[[Page 18314]]
Table 3--Estimated One-Time Reporting Burden
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
21 CFR section; activity Number of responses per Total responses Average burden Total hours
respondents respondent per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
514.8 and 514.8(c)(2); supplements and changes to an approved 66 \1\ 12.55 \2\ 828 20 16,560
application.......................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Decimal rounded up.
\2\ Decimal rounded down.
To ease the burden of the information collection on respondents, we
have established a 6-year implementation period. We estimate 828
supplemental labeling applications of approved and marketed new animal
drugs over the course of 6 years to comply with the labeling
regulations, if finalized. Based on internal data, there were 78 unique
firms with an approved or conditionally approved new animal drug
application (sponsors) in September 2023. Sixty-six of these sponsors
currently had an approved and marketed new animal drug. We assume 828
submissions regarding supplements and changes to an application for an
approved and marketed new animal drug, for an average of 12.55
submissions per respondent. We further assume it takes an average of 20
hours to prepare each submission for a total of 16,560 hours.
Table 4--Estimated One-Time Recordkeeping Burden
----------------------------------------------------------------------------------------------------------------
Number of Average burden
Activity Number of records per Total annual per Total hours
Recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
Reading and understanding the 156 1 156 6 936
rule..........................
Writing new labeling SOPs...... 156 1 156 2.14 \1\ 334
Training....................... 156 1 156 0.89 \1\ 139
--------------------------------------------------------------------------------
Total...................... ............... .............. .............. .............. 1,409
----------------------------------------------------------------------------------------------------------------
\1\ Decimal rounded up.
We estimate that approved new animal drug sponsors will incur one-
time burden attributable to reading and understanding the rule,
revising SOPs related to labeling, and training employees on the
revised SOPs. We estimate the average time to read and understand the
proposed rule is 6 hours (156 x 6 = 936 hours). We estimate that small
businesses will spend 4 hours and large business will spend 8 hours
revising SOPs related to labeling. Based on data from the 2017
Statistics of U.S. Businesses, there are 72 small business entities and
6 large business entities. ((72 x 4) + (6 x 8) / 156 = 2.14 hours per
record). We also estimate that small businesses will spend 1 hour and
large businesses will spend 12 hours to train employees on the revised
SOPs ((72 x 1) + (6 x 12) / 156 = 0.89 hours per record). We assume at
least two recordkeepers per drug sponsor.
To ensure that comments on information collection are received, OMB
recommends that written comments be submitted through reginfo.gov (see
ADDRESSES). All comments should be identified with the title of the
information collection.
In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3407(d)), we have submitted the information collection provisions of
this proposed rule to OMB for review. These information collection
requirements will not be effective until FDA publishes a final rule,
OMB approves the information collection requirements, and the rule goes
into effect. FDA will announce OMB approval of these requirements in
the Federal Register.
X. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132: Federalism. The Order
requires Federal Agencies to examine actions carefully to determine if
they contain policies that have federalism implications or that preempt
State law. As defined in the Order, ``policies that have federalism
implications'' refers to regulations, legislative comments or proposed
legislation, and other policy statements or actions that have
substantial direct effects on the States, on the relationship between
the Federal Government and the States, or on the distribution of power
and responsibilities among the various levels of government.
Section 4(a) of the Order requires Agencies to ``construe . . . a
Federal statute to preempt State law only where the statute contains an
express preemption provision or there is some other clear evidence that
the Congress intended preemption of State law, or where the exercise of
State authority conflicts with the exercise of Federal authority under
the Federal statute.'' The sole statutory provision giving preemptive
effect to this proposed rule is section 751 of the FD&C Act (21 U.S.C.
379r), which would apply only with respect to nonprescription animal
drugs. There are no express preemption provisions of the FD&C Act
applicable to prescription animal drugs.
We have complied with all of the applicable requirements under the
Executive order and have determined that the preemptive effect of this
proposed rule, if finalized, would be consistent with Executive Order
13132. Through publication of this proposed rule, we are providing
notice and an opportunity for State and local officials to comment on
this rulemaking.
XI. Consultation and Coordination With Indian Tribal Governments
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule does not contain policies that would have a
substantial direct effect on one or more Indian Tribes, on the
relationship between the Federal Government and Indian Tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian Tribes. The
[[Page 18315]]
Agency solicits comments from tribal officials on any potential impact
on Indian Tribes from this proposed action.
XII. References
The following references are on display in the Dockets Management
Staff (see ADDRESSES) and are available for viewing by interested
persons between 9 a.m. and 4 p.m. Monday through Friday; they are also
available electronically at https://www.regulations.gov. Although FDA
has verified the website addresses in this document, please note that
websites are subject to change over time.
1. FDA, Preliminary Regulatory Impact, Initial Regulatory
Flexibility, and Unfunded Mandates Reform Act Analyses, 2023; Docket
No. FDA-2023-N-5160; https://www.fda.gov/about-fda/economics-staff/regulatory-impact-analyses-ria.
List of Subjects
21 CFR Part 201
Drugs, Labeling, Reporting and Recordkeeping requirements.
21 CFR Part 500
Animal drugs, Animal feeds, Cancer, Labeling, Packaging and
containers, Polychlorinated biphenyls (PCB's).
21 CFR Part 501
Animal foods, Packaging and containers, Reporting and recordkeeping
requirements.
21 CFR Part 510
Administrative practice and procedure, Animal drugs, Labeling,
Reporting and recordkeeping requirements.
21 CFR Parts 514 and 516
Administrative practice and procedure, Animal drugs, Confidential
business information, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, we propose
that 21 CFR parts 201, 500, 501, 510, 514, and 516 be amended as
follows:
PART 201--LABELING
0
1. The authority citation for part 201 is revised to read as follows:
Authority: 21 U.S.C. 321, 331, 343, 351, 352, 353, 354, 355,
358, 360, 360b, 360ccc, 360ccc-1, 360ee, 360gg-360ss, 371, 374,
379e; 42 U.S.C. 216, 241, 262, 264.
0
2. In Sec. 201.15, add paragraph (c)(4) to read as follows:
Sec. 201.15 Drugs; prominence of required label statements.
* * * * *
(c) * * *
(4) Approved or conditionally approved new animal drugs are
exempted from the requirements in paragraph (c). Foreign language
translations of the labeling for approved or conditionally approved new
animal drugs must comply with Sec. 201.404(i) and (j).
Sec. 201.100 [Amended].
0
3. In Sec. 201.100, in paragraph (d) introductory text remove the
words, ``and Sec. 201.105(b)(2)''.
0
4. Revise Sec. 201.105 to read as follows:
Sec. 201.105 Prescription drugs for animal use.
A drug subject to the requirements of section 503(f)(1) of the
Federal Food, Drug, and Cosmetic Act is exempt from section 502(f)(1)
of the Federal Food, Drug, and Cosmetic Act if all the following
conditions are met:
(a) The prescription animal drug is:
(1)(i) In the possession of a person, or the person's agents or
employees, regularly and lawfully engaged in the manufacture,
transportation, storage, or wholesale distribution of drugs that are to
be used only by or on the prescription or other order of a licensed
veterinarian; or
(ii) In the possession of a retail, hospital, or clinic pharmacy,
or other person authorized under State law to dispense prescription
animal drugs, who is regularly and lawfully engaged in dispensing drugs
that are to be used only by or on the prescription or other order of a
licensed veterinarian; or
(iii) In the possession of a licensed veterinarian for use in the
course of his or her professional practice; and
(2) To be dispensed in accordance with section 503(f) of the
Federal Food, Drug, and Cosmetic Act.
(b) For prescription new animal drugs approved under section 512 of
the Federal Food, Drug, and Cosmetic Act or conditionally approved
under section 571 of the Federal Food, Drug, and Cosmetic Act:
(1) The labeling components identified in Sec. 201.405 for the
prescription new animal drug:
(i) Contain adequate information for its use, including indications
for use, dosages, routes of administration, frequency and duration of
administration, and any relevant contraindications, warnings,
precautions, and adverse reactions, under which veterinarians licensed
by law to administer the drug can use the drug safely and for the
purposes for which it is intended, including all purposes for which it
is advertised or represented;
(ii) Are authorized by the approved new animal drug application or
the conditionally approved new animal drug application for the
prescription new animal drug; and
(iii) Comply with the applicable content and format requirements of
subpart H of this part.
(2) Any labeling, as defined in section 201(m) of the Federal Food,
Drug, and Cosmetic Act, for the approved or conditionally approved
prescription new animal drug, distributed by or on behalf of the
manufacturer, packer, or distributor of the drug, that provides or
purports to provide information for its use or a dosage for its use
contains:
(i) Adequate information for such use, including indications for
use, dosages, routes of administration, frequency and duration of
administration, and any relevant contraindications, warnings,
precautions, and adverse reactions, and information relevant to
compliance with the new animal drug provisions of the Federal Food,
Drug, and Cosmetic Act, under which veterinarians licensed by law to
administer the drug can use the drug safely and for the purposes for
which it is intended, including all conditions for which it is
advertised or represented, and the labeling components providing such
information for use are the same in language and emphasis as labeling
authorized by the approved new animal drug application or the
conditionally approved new animal drug application, and any other
labeling components are consistent with and not contrary to such
authorized labeling; and
(ii) The same information concerning the ingredients of the drug as
appears on the labeling authorized by the approved new animal drug
application or the conditionally approved new animal drug application.
(c) For prescription new animal drugs listed in the index of
legally marketed unapproved new animal drugs for minor species
established under section 572 of the Federal Food, Drug, and Cosmetic
Act, or prescription animal drugs not subject to an approved or
conditionally approved application or indexed listing:
(1) The label of the drug bears:
(i) The statement, ``Caution: Federal law restricts this drug to
use by or on the order of a licensed veterinarian'';
(ii) The recommended or usual dosage;
(iii) The route of administration, if it is not for oral use;
(iv) The quantity or proportion of each active ingredient as well
as the information required by section 502(e)
[[Page 18316]]
of the Federal Food, Drug, and Cosmetic Act; and
(v) If it is for other than oral use, the names of all inactive
ingredients, except that:
(A) Flavorings and perfumes may be designated as such without
naming their components;
(B) Color additives may be designated as coloring without naming
specific color components unless the naming of such components is
required by a color additive regulation prescribed in subchapter A of
this chapter; and
(C) Trace amounts of harmless substances added solely for
individual product identification need not be named.
(vi) If it is intended for administration by parenteral injection,
the quantity or proportion of all inactive ingredients, except that
ingredients added to adjust the pH or to make the drug isotonic may be
declared by name and a statement of their effect; and if the vehicle is
water for injection, it need not be named.
(vii) An identifying lot or control number from which it is
possible to determine the complete manufacturing history of the package
of the drug.
(viii) In the case of containers too small or otherwise unable to
accommodate a label with sufficient space to bear all of the
information required by paragraph (c)(1) of this section, but which are
packaged within an outer container from which they are removed for
dispensing or use, the information required by paragraphs (c)(1)(ii),
(iii), (v), and (vi) of this section may be contained in other labeling
on or within the package from which the drug is to be so dispensed, and
the information referred to in paragraph (c)(1)(i) of this section may
be placed on such outer container only, and the information required by
paragraph (c)(1)(vii) of this section may be placed on the crimp of the
dispensing tube.
(2) The labeling on or within the package from which the drug is to
be dispensed:
(i) Bears adequate information for its use, including indications
for use, dosages, routes of administration, frequency and duration of
administration, and any relevant contraindications, warnings,
precautions, and adverse reactions, under which veterinarians licensed
by law to administer the drug can use the drug safely and for the
purposes for which it is intended, including all purposes for which it
is advertised or represented; and
(ii) For prescription new animal drugs listed in the index of
legally marketed unapproved new animal drugs for minor species
established under section 572 of the Federal Food, Drug, and Cosmetic
Act, the labeling bearing such information is the labeling contained in
the index listing.
(3) Any labeling, as defined in section 201(m) of the Federal Food,
Drug, and Cosmetic Act, whether or not it is on or within a package
from which the drug is to be dispensed, distributed by or on behalf of
the manufacturer, packer, or distributor of the drug, that provides or
purports to provide information for use or which prescribes,
recommends, or suggests a dosage for the use of the drug (other than
dose information required by paragraph (c)(1)(ii) of this section)
contains:
(i) Adequate information for such use, including indications for
use, dosages, routes of administration, frequency and duration of
administration, and any relevant contraindications, warnings,
precautions, and adverse reactions, including information relevant to
compliance with the new animal drug provisions of the Federal Food,
Drug, and Cosmetic Act, under which veterinarians licensed by law to
administer the drug can use the drug safely and for the purposes for
which it is intended, including all conditions for which it is
advertised or represented; for prescription new animal drugs listed in
the index of legally marketed unapproved new animal drugs for minor
species established under section 572 of the Federal Food, Drug, and
Cosmetic Act, the labeling components providing such information are
the same in language and emphasis as labeling indexed under the
provisions of section 572 of the Federal Food, Drug, and Cosmetic Act,
and any other labeling components are consistent with and not contrary
to such indexed labeling; and
(ii) The same information concerning the ingredients of the drug as
appears on the label and labeling on or within the package from which
the drug is to be dispensed.
(4) All labeling, except labels and cartons, bearing information
for use of the drug also bears the date of the issuance or the date of
the latest revision of such labeling.
(d) Reminder labeling, which calls attention to the name of the
prescription animal drug product but does not include indications or
dosage recommendations for use of the drug product, is exempted from
the provisions of paragraphs (b) and (c) of this section. This reminder
labeling must contain only the proprietary name of the drug product, if
any; the established name of the drug product, if any; the established
name of each active ingredient in the drug product; and, optionally,
information relating to quantitative ingredient statements, dosage
form, quantity of package contents, price, the name and address of the
manufacturer, packer, or distributor or other written, printed, or
graphic matter containing no representation or suggestion relating to
the drug product. If the Commissioner finds that there is evidence of
significant incidence of fatalities or serious injury associated with
the use of a particular prescription animal drug, the Commissioner may
withdraw this exemption by so notifying the manufacturer, packer, or
distributor of the drug by letter. Reminder labeling, other than price
lists and catalogs solely intended to convey price information, is not
permitted for a prescription animal drug product whose labeling
contains a boxed warning relating to a serious hazard associated with
the use of the drug product.
0
5. Add subpart H, consisting of Sec. Sec. 201.401 through 201.413, to
read as follows:
Subpart H--Labeling Requirements for Approved or Conditionally Approved
New Animal Drugs
Sec.
201.401 Scope.
201.403 Definitions.
201.404 General requirements.
201.405 Content and format for prescription new animal drug
labeling.
201.407 Content and format for over-the-counter (OTC) new animal
drug labeling.
201.409 Content and format of labeling for new animal drugs for use
in animal feeds.
201.411 Exemptions from labeling requirements for approved or
conditionally approved new animal drugs.
201.413 Labeling requirements for certain approved or conditionally
approved new animal drugs.
Subpart H--Labeling Requirements for Approved or Conditionally
Approved New Animal Drugs
Sec. 201.401 Scope.
(a) This subpart establishes requirements for content and format of
labeling for the following categories of prescription (Rx) new animal
drugs, over-the-counter (OTC) new animal drugs other than those for use
in animal feeds in accordance with part 558 of this chapter, and new
animal drugs for use in animal feeds that are subject to part 558 of
this chapter, including veterinary feed directive (VFD) drugs:
(1) New animal drugs that are the subject of a new animal drug
application (NADA) approved or submitted pursuant to section 512 of the
Federal Food, Drug, and Cosmetic Act;
(2) New animal drugs that are the subject of an application for
conditional
[[Page 18317]]
approval (CNADA) conditionally approved or submitted pursuant to
section 571 of the Federal Food, Drug, and Cosmetic Act;
(3) Generic new animal drugs that are the subject of an abbreviated
new animal drug application (ANADA) approved or submitted pursuant to
section 512(n) of the Federal Food, Drug, and Cosmetic Act that
references a new animal drug for which the NADA has been voluntarily
withdrawn for reasons other than safety or effectiveness, or that
references a new animal drug for which the NADA has been withdrawn on
the basis of one or more of the grounds included under section 512(e)
of the Federal Food, Drug, and Cosmetic Act and for which the generic
new animal drug's approval was not affected by the withdrawal; and
(4) New animal drugs for use in proprietary medicated feeds for
which the labeling is maintained in a Veterinary Master File (VMF).
Proprietary medicated feeds for which the labeling is maintained in an
NADA or CNADA are included within the categories of drugs described in
paragraphs (a)(1) and (2) of this section.
(b) The provisions of this subpart apply to the applications
described in paragraphs (a)(1) through (4) of this section for new
animal drugs that are approved before the [EFFECTIVE DATE OF THE FINAL
RULE], pending on the [EFFECTIVE DATE OF THE FINAL RULE], or submitted
on or after the [EFFECTIVE DATE OF THE FINAL RULE], in accordance with
the schedule in Sec. 201.404(a)(4).
(c) Any new animal drug subject to this subpart that does not fully
comply with the applicable requirements of this subpart in accordance
with the schedule in Sec. 201.404(a)(4) is deemed to be misbranded
under section 502 of the Federal Food, Drug, and Cosmetic Act and, if
that drug is a VFD drug, also under section 504(b) of the Federal Food,
Drug, and Cosmetic Act.
(d) The provisions of this subpart do not apply to:
(1) Legally marketed unapproved new animal drugs for minor species
that are indexed in accordance with section 572 of the Federal Food,
Drug, and Cosmetic Act;
(2) Heritable intentional genomic alterations in animals; and
(3) Promotional labeling or advertising.
Sec. 201.403 Definitions.
The following definitions apply to this subpart H.
Active ingredient has the same meaning as given in Sec.
210.3(b)(7) of this chapter.
Active moiety means the molecule or ion, excluding those appended
portions of the molecule that cause the drug to be an ester, salt
(including a salt with hydrogen or coordination bonds), or other
noncovalent derivative (such as a complex, chelate, or clathrate) of
the molecule, responsible for the physiological or pharmacological
action of the drug substance.
Adverse drug experience has the same meaning as given in Sec.
514.3 of this chapter.
Adverse reaction means an undesirable effect, reasonably associated
with the use of the drug product, that may occur as part of the
pharmacological action of the drug or that may be unpredictable in
occurrence.
ANADA has the same meaning as given in Sec. 514.3 of this chapter.
Boxed warning means certain contraindications or serious warnings,
particularly those that may lead to death or serious injury to animals
or humans that must be presented in a box on labeling. The box and its
contents must be bolded. The boxed warning is ordinarily based on data
from the target animal, but data from other species may also be used.
Contraindication means any situation in which the new animal drug
should not be used because the risk of use (e.g., certain potentially
fatal adverse reactions) clearly outweighs any possible benefit to the
animal. Those situations may include use of the drug in animals that,
because of their particular species, class, breed, age, sex,
concomitant therapy, disease state, or other condition such as
pregnancy or lactation, have a substantial risk of being harmed by the
drug and for which no potential benefit makes the risk acceptable.
Contraindications include only known hazards.
Drug product has the same meaning as given in Sec. 210.3(b)(4) of
this chapter.
Environmental warning means a warning that identifies any potential
hazard to the human environment associated with the use of the new
animal drug.
Established name has the same meaning as given in section 502(e)(3)
of the Federal Food, Drug, and Cosmetic Act.
Extralabel use has the same meaning as given in Sec. 530.3(a) of
this chapter.
Field study means a type of adequate and well-controlled study
designed to assess the effectiveness and/or safety of a new animal drug
in the target animal under conditions that closely approximate the
actual conditions of use.
Free-choice medicated feed has the same meaning as given in Sec.
510.455(a) of this chapter.
Full prescribing information means all information necessary for
the safe and effective use of a Rx new animal drug.
Full product information means all information necessary for the
safe and effective use of an OTC new animal drug.
Immediate container means the container in contact with the new
animal drug. The term ``immediate container'' does not include package
liners (section 201(l) of the Federal Food, Drug, and Cosmetic Act).
Inactive ingredient has the same meaning as given in Sec.
210.3(b)(8) of this chapter.
Indication means the use for which the new animal drug is approved
or conditionally approved.
Label has the same meaning as given in section 201(k) of the
Federal Food, Drug, and Cosmetic Act.
Labeling has the same meaning as given in section 201(m) of the
Federal Food, Drug, and Cosmetic Act.
Lot number, control number, or batch number has the same meaning as
given in Sec. 210.3(b)(11) of this chapter.
Milk discard time means the interval between the time of the last
administration of a new animal drug and the time when the milk can be
safely consumed.
NADA has the same meaning as given in Sec. 514.3 of this chapter.
New animal drug has the same meaning as given in section 201(v) of
the Federal Food, Drug, and Cosmetic Act.
Package insert means a labeling component that contains full
prescribing information for Rx new animal drugs or full product
information for OTC new animal drugs and is included with the immediate
container or secondary container or is attached to the label.
Precaution means any special care to be exercised for safe and
effective use of the new animal drug. This may include recommended
screening, monitoring, or diagnostic tests.
Representative Type B medicated feed labeling means template
labeling (also known as ``Blue Bird labels,'' 64 FR 63197, November 19,
1999) approved by FDA as part of the new animal drug application or an
application for conditional approval for a Type A medicated article for
the preparation of final printed labels (for medicated feed bags) or
labeling (accompanying bulk medicated feed) for Type B medicated feeds
containing the new animal drug. Representative Type B medicated feed
labeling provides the minimum
[[Page 18318]]
information that must be included on the final printed labels or
labeling for Type B medicated feeds.
Representative Type C medicated feed labeling means template
labeling (also known as ``Blue Bird labels,'' 64 FR 63197, November 19,
1999) approved by FDA as part of the new animal drug application or an
application for conditional approval for a Type A medicated article or
proprietary Type B medicated feed for the preparation of final printed
labels (for medicated feed bags) or labeling (accompanying bulk
medicated feed) for Type C medicated feeds containing the new animal
drug. Representative Type C medicated feed labeling provides the
minimum information that must be included on the final printed labels
or labeling for Type C medicated feeds.
Residue warning statement means a statement that warns against the
use of the new animal drug in animals for which the withdrawal period
and/or milk discard time has not been determined, and/or provides other
information to prevent illegal drug residues in food products from
animals treated with the new animal drug.
Secondary container means the packaging that surrounds the
immediate container for a new animal drug.
Shipping labeling means labeling associated with the outermost
carton containing immediate containers, secondary containers, and/or
multiple unit (multi-unit) cartons of a new animal drug and intended
for shipment, but not display, of the product.
Small label means a label on an immediate container for a new
animal drug that has insufficient space to accommodate the information
required for a label by Sec. 201.405(b) for Rx new animal drugs or
Sec. 201.407(b) for OTC new animal drugs.
Sponsor has the same meaning as given in Sec. 510.3(k) of this
chapter.
Strength has the same meaning as given in Sec. 210.3(b)(16) of
this chapter.
Target animal means the species, or collection of species, of
animals, and, if applicable, the specific subset(s) of animals (e.g.,
life stage, production class, age, gender) for which the new animal
drug is approved or conditionally approved.
Type A medicated article has the same meaning as given in Sec.
558.3(b)(2) of this chapter.
Type B medicated feed has the same meaning as given in Sec.
558.3(b)(3) of this chapter.
Type C medicated feed has the same meaning as given in Sec.
558.3(b)(4) of this chapter.
User safety warning means a warning that identifies any serious
adverse reaction or potential hazard to human health associated with
human exposure during use of a new animal drug via contact, inhalation,
ingestion, injection, or by other means.
Veterinary feed directive (VFD) has the same meaning as given in
Sec. 558.3(b)(7) of this chapter.
VFD drug has the same meaning as given in Sec. 558.3(b)(6) of this
chapter.
Warning means any serious adverse reaction or potential hazard
associated with the use of the new animal drug.
Withdrawal period means the interval between the time of the last
administration of a new animal drug and the time when the animal can be
safely slaughtered for food.
Sec. 201.404 General requirements.
(a) The labeling of a new animal drug subject to these regulations
as identified in Sec. 201.401(a):
(1) Must conform to an application approved under section 512 of
the Federal Food, Drug, and Cosmetic Act or conditionally approved
under section 571 of the Federal Food, Drug, and Cosmetic Act.
(2) Must be informative and accurate and neither promotional in
tone nor false or misleading in any particular.
(3) Must be updated if new information becomes available that
causes the labeling to become inaccurate, false, or misleading, in
accordance with Sec. 514.8 of this chapter.
(4) Must conform to this subpart in accordance with the earliest
applicable compliance date provided in the following schedule, unless
paragraphs (b), (c), or (d) of this section are applicable.
Table 1 to Paragraph (a)(4)
------------------------------------------------------------------------
All conforming labeling must be
Application No. and/or status submitted:
------------------------------------------------------------------------
(i) NADA, CNADA, or a supplement to an As part of the application or
NADA or CNADA subject to Sec. supplemental application
514.8(c)(2) submitted after [effective
date of the final rule plus 180 days].
(ii) NADA, CNADA, or a supplement to an As part of the application or
NADA or CNADA subject to Sec. supplemental application; or,
514.8(c)(2) pending on [effective date as a supplement to an approved
of the final rule] or submitted application or supplemental
between [effective date of the final application no later than 180
rule] and [effective date of the final days after the approval date
rule plus 180 days]. of the application or
supplemental application
(iii) NADA number 141-300 or greater As a supplement to an approved
and originally approved before application between [effective
[effective date of the final rule]; or date of the final rule plus 1
ANADA that references an NADA (1) year] and [effective date of
voluntarily withdrawn for reasons the final rule plus 2 years]
other than safety and effectiveness,
or (2) withdrawn under section 512(e)
of the Federal Food, Drug, and
Cosmetic Act and the ANADA's approval
was not affected by the withdrawal.
(iv) NADA number 141-000 to 141-299.... As a supplement to an approved
application between [effective
date of the final rule plus 2
years] and [effective date of
the final rule plus 3 years]
(v) NADA number 115-000 to 140-999..... As a supplement to an approved
application between [effective
date of the final rule plus 3
years] and [effective date of
the final rule plus 4 years]
(vi) NADA number 45-000 to 114-999..... As a supplement to an approved
application between [effective
date of the final rule plus 4
years] and [effective date of
the final rule plus 5 years]
(vii) NADA number 1 to 44-999.......... As a supplement to an approved
application between [effective
date of the final rule plus 5
years] and [effective date of
the final rule plus 6 years]
------------------------------------------------------------------------
[[Page 18319]]
(b) For proprietary Type B or Type C medicated feeds in which the
underlying data and labeling are maintained in a VMF, a submission
containing the conforming labeling must be made to the VMF within 180
days after all conforming labeling has been approved for the NADA or
CNADA that is the approved or conditionally approved source of the new
animal drug used to manufacture the proprietary medicated feed.
(c) Unless a supplement subject to Sec. 514.8(c)(2) of this
chapter is submitted to a CNADA after the [effective date of the final
rule], new animal drugs conditionally approved before [effective date
of the final rule] are not required to conform to this subpart until an
application for full approval is submitted.
(d) For combination new animal drugs subject to section 512(d)(4)
of the Federal Food, Drug, and Cosmetic Act that are approved for use
in animal feed or drinking water on or before [effective date of the
final rule], a supplement containing the conforming labeling for the
combination new animal drug must be submitted within 180 days after all
conforming labeling has been approved for the individual new animal
drugs in the combination.
(e) In those circumstances where it may not be clear how a
requirement in this subpart applies to a particular new animal drug, or
whether it applies, the final determination will be made by FDA.
(f) When submitting labeling for the purposes of conforming to the
requirements of subpart H according to the schedule in paragraph (a)(4)
of this section, all labeling components for the approved or
conditionally approved new animal drug must be provided in one
submission. FDA will refuse to file labeling submissions intended to
conform to this subpart if they are incomplete.
(g) All labeling for an approved or conditionally approved new
animal drug must comply with the general formatting requirements
described in this paragraph in addition to all content and formatting
requirements described in this subpart.
(1) Placement of the established name relative to the proprietary
name on labeling for approved or conditionally approved Rx new animal
drugs must comply with Sec. 201.10(g)(1). Size and prominence of the
established name relative to the proprietary name must comply with
section 502(e)(1)(B) of the Federal Food, Drug, and Cosmetic Act and
Sec. 201.10(g)(2).
(2) Placement, size, and prominence of the established name
relative to the proprietary name on the labeling for approved or
conditionally approved OTC new animal drugs and the labeling for
approved or conditionally approved new animal drugs for use in animal
feeds (Type A medicated article label, proprietary Type B medicated
feed label, proprietary Type C medicated feed label, other approved
labeling associated with a Type A medicated article), excluding
representative Type B and Type C medicated feed labeling, must comply
with the following requirements:
(i) The proprietary name of the new animal drug must be accompanied
by the established name each time the proprietary name is featured on
the labeling, except in running text. Running text includes detailed
information such as found in warnings and directions. On any panel or
page of a component of labeling in which the proprietary name is not
featured elsewhere but is used in the running text, the established
name must be placed in conjunction with the proprietary name at least
with the first presentation of the proprietary name in running text.
(ii) Where the established name accompanies the proprietary name,
it must be placed directly to the right of, or directly below, the
proprietary name. Except for trademark symbols associated with the
proprietary name, the proprietary name and the established name must
not be separated by placement of intervening matter that, in any way,
detracts from, obfuscates, or de-emphasizes the established name of the
product, or obscures the relationship between the proprietary name and
the established name. The established name must be presented entirely
within parentheses.
(iii) Except in running text, where the established name
accompanies the proprietary name, the smallest letter of the
established name (upper or lower case letters) must be printed in
letters at least half the size of the largest letter of the proprietary
name (upper or lower case letters). Within running text, the
established name accompanying the proprietary name must be printed in
letters the same size of the letters in the proprietary name (upper and
lower case letters). The prominence of the established name must be
consistent with the prominence of the proprietary name, taking into
account all pertinent factors including typography, layout, contrast,
and other printing features.
(3) For representative Type B and Type C medicated feed labeling
for approved or conditionally approved new animal drugs for use in
animal feeds, the established name of the Type B or Type C medicated
feed presented below the description of the Type B or Type C medicated
feed must comply with the following requirements:
(i) The established name must be presented directly below the
description of the Type B or Type C medicated feed and must not be
separated by placement of intervening matter.
(ii) The established name must be printed in lower case letters
except for ``Type B'' or ``Type C''.
(iii) The established name must be printed in non-bold font of the
same size letters as the name of the Type B or Type C medicated feed
(upper and lower case letters).
(iv) The established name must be presented entirely within
parentheses.
(4) All labeling text and type style must be easy to read, and
letters must not touch.
(5) Running text, section headings, and subsection headings on
package inserts and representative Type B and Type C medicated feed
labeling must be in black and on a white background and use a single
type style. For other labeling components, other color combinations may
be used if there is sufficient contrast between text and the background
colors to ensure readability of the text.
(6) Representative Type B and Type C medicated feed labeling must
not contain any logos, graphics, or designs other than illustrations or
tables that FDA determines are necessary for proper use of the
medicated feed. For other labeling components for approved or
conditionally approved new animal drugs, in accordance with Sec.
201.15(b)(1), graphics or designs associated with the labeling must not
take up space needed for information required by this subpart. In
accordance with paragraph (a)(2) of this section, graphics or diagrams
must not be promotional in tone. If graphics are incorporated into the
background, for any text appearing over the graphics, there must be
sufficient contrast between the text and the graphics colors to ensure
readability of the text. The use of compressed arrows on labeling is
limited to the subsection entitled either ``Withdrawal Periods and
Residue Warnings'' or ``Withdrawal Periods,'' in accordance with
paragraph (g)(8)(iii) of this section.
(7) The following minimum letter height or type size must be used
for specific components of labeling, subject to the provisions of
paragraph (g)(2) of this section:
(i) Immediate container label, secondary container labeling,
package inserts, and labeling of multiple unit cartons and display
cartons: 8 points.
(ii) Small label: 6 points.
[[Page 18320]]
(iii) Type A medicated article label, representative Type B
medicated feed labeling, representative Type C medicated feed labeling,
proprietary Type B medicated feed label, and proprietary Type C
medicated feed label: 10 points.
(iv) Additional labeling for Rx new animal drugs that is to be
provided to the animal owner: 12 points.
(v) Shipping labeling for Rx and OTC new animal drugs and other
approved labeling for Type A medicated articles: 16 points.
(8) Section headings and subsection headings must be formatted as
follows:
(i) All section headings and subsection headings must be in bold
type that prominently distinguishes them from other approved labeling
information.
(ii) Section headings must be either left justified or centered.
(iii) For the subsection entitled either ``Withdrawal Periods and
Residue Warnings'' or ``Withdrawal Periods,'' the subsection heading,
and the contents of the subsection, must be centered within compressed
arrows.
(iv) All other subsection headings must be left justified.
(h) If the National Drug Code (NDC) is included on labeling, it
must appear in accordance with Sec. 207.33 of this chapter.
(i) All words, statements, and other information required on the
labeling for approved or conditionally approved new animal drugs must
appear in the English language. Additional translations of labeling for
approved or conditionally approved new animal drugs into foreign
languages must comply with the following requirements:
(1) For approved or conditionally approved Rx new animal drugs, if
a labeling component contains any section or wording translated into a
foreign language, then the entire full prescribing information must be
translated into the foreign language and must comply with the format
and content requirements in Sec. 201.405(a). FDA also may require
additional wording on other labeling components for the Rx new animal
drug to be translated into the foreign language when necessary to
ensure its safe and effective use.
(2) For approved or conditionally approved OTC new animal drugs
other than new animal drugs for use in animal feeds, if a labeling
component contains any section or wording translated into a foreign
language, then the entire full product information must be translated
into the foreign language and must comply with the format and content
requirements in Sec. 201.407(a). FDA also may require additional
wording on other labeling components for the OTC new animal drug to be
translated into the foreign language when necessary to ensure its safe
and effective use.
(3) For approved or conditionally approved new animal drugs for use
in animal feeds, if the labeling contains any section or wording
translated into a foreign language, then all labeling must be
translated into the foreign language and must comply with the format
and content requirements in Sec. 201.409.
(4) FDA may limit the number of languages into which labeling
information is translated to ensure clarity of information and the safe
and effective use of the new animal drug.
(j) For approved or conditionally approved new animal drugs
distributed solely in the Commonwealth of Puerto Rico or in a Territory
where the predominant language is other than English, the predominant
language may be substituted for English. Such new animal drugs may be
exempt from paragraph (i) of this section.
Sec. 201.405 Content and format for prescription (Rx) new animal
drug labeling.
This section describes specific content and format requirements for
the labeling of approved or conditionally approved Rx new animal drugs.
This section does not apply to new animal drugs approved or
conditionally approved as veterinary feed directive (VFD) drugs. See
Sec. 201.409 for content and format requirements for the labeling of
approved or conditionally approved new animal drugs for use in animal
feeds that are subject to part 558 of this chapter, including VFD
drugs. Omit labeling sections or subsections that do not apply to the
Rx new animal drug. The final content of each applicable component and
section of labeling is determined by FDA. In addition to the content
and format requirements in this section, the labeling of approved or
conditionally approved Rx new animal drugs must comply with other
applicable requirements in this subpart.
(a) Labeling providing full prescribing information. All approved
or conditionally approved Rx new animal drugs must provide full
prescribing information as described in this paragraph. The package
insert must include full prescribing information. If no package insert
is provided, a secondary container is required, and its labeling must
include full prescribing information as described in this paragraph.
The following information, as applicable, must appear in the order
listed on the labeling component providing full prescribing
information. If full prescribing information is provided on the
secondary container labeling, in accordance with section 201(k) of the
Federal Food, Drug, and Cosmetic Act, the secondary container labeling
may exclude any of the information described in this subsection that is
required by paragraphs (b) or (c) of this section to appear on the
label if such information is easily legible through the secondary
container. Section headings, subsection headings, and other text
presented in quotations in this paragraph must appear verbatim on the
labeling providing full prescribing information. Sections and
subsections are not numbered on full prescribing information.
(1) Drug product identification. This section of full prescribing
information must include:
(i) The proprietary name of the finished drug product;
(ii) The established name of the drug product;
(iii) The route(s) of administration, if not included as part of
the established name of the drug product;
(iv) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(v) The established name and strength or concentration of each
active ingredient, except that the strength or concentration may be
excluded from full prescribing information provided on a package insert
that applies to multiple strengths or concentrations;
(vi) The pharmacological class of the new animal drug, if required
to facilitate the drug's safe and effective use; and
(vii) For controlled substances, the required controlled substance
symbol, in accordance with part 1302 of this title designating the
schedule for the drug substance.
(2) Prescription statement. This section of full prescribing
information must include the following statement: ``Caution: Federal
law restricts this drug to use by or on the order of a licensed
veterinarian''.
(3) Conditional approval statement. All conditionally approved new
animal drugs must include the following statement in this section of
full prescribing information in accordance with section 571(f)(1)(A) of
the Federal Food, Drug, and Cosmetic Act: ``conditionally approved by
FDA pending a full demonstration of effectiveness under application
number [insert number]''. This statement must be prominent and
conspicuous.
(4) Boxed warnings. All Rx new animal drugs with boxed warnings
must include the boxed warning in this section of full prescribing
information.
[[Page 18321]]
The box must contain, in upper case letters, the heading ``WARNING''.
The contents of the box must briefly explain the risk and, if
appropriate, refer to more detailed information in other sections of
full prescribing information. The box, heading, and contents must be
bolded.
(5) Extralabel use prohibition statement. An approved new animal
drug that is prohibited from extralabel use as listed under Sec.
530.41 of this chapter must include in this section of full prescribing
information an extralabel use prohibition statement that begins with
the phrase: ``Federal law prohibits the extralabel use of this drug . .
.'' and concludes with a description of the prohibition as described in
Sec. 530.41 of this chapter.
(6) ``Description''. This section of full prescribing information
must include:
(i) The proprietary name of the finished drug product;
(ii) The established name of the drug product;
(iii) The route(s) of administration, if not included as part of
the established name of the drug product;
(iv) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(v) A description of the identifying characteristics of the dosage
form, such as color, shape, coating, scoring, and imprinting;
(vi) The established name and strength or concentration of each
active ingredient, including all available strengths or concentrations
to which full prescribing information applies;
(vii) If applicable, a statement that the product is sterile; and
(viii) The established name of each inactive ingredient presented
in decreasing order of predominance, by weight or concentration.
(A) If exemption from listing one or more inactive ingredients is
granted, in accordance with Sec. 201.411, to avoid disclosure of trade
secret information, this section of full prescribing information must
also state the following: ``Certain inactive ingredients are not listed
to avoid disclosing trade secret information.''
(B) If exemption from listing one or more inactive ingredients is
granted, in accordance with Sec. 201.411, because their listing would
be impracticable, this section of full prescribing information must
also state the following: ``Certain inactive ingredients are not listed
because their listing would be impracticable.''
(7) ``Indications for Use''. Include the following information in
this section of full prescribing information in order:
(i) The approved or conditionally approved indication(s) and target
animal(s) in the following format: ``For [indication(s)] in [target
animal(s)]'';
(ii) A statement indicating that the new animal drug is approved or
conditionally approved for use only under specific conditions, if
applicable; and
(iii) A statement(s) indicating animals for which the new animal
drug is not approved or conditionally approved, if FDA determines such
a statement(s) is required for safety and/or effectiveness reasons.
(8) ``Dosage and Administration''. This section of full prescribing
information must include for each indication and target animal:
(i) The statement, ``Always provide [additional labeling] with each
prescription'' for Rx new animal drugs requiring additional labeling,
in accordance with paragraph (a)(14) of this section, inserting the
title of the additional labeling in the location indicated by the
bracketed text;
(ii) The route(s) of administration, and specific site(s) of
administration, if applicable;
(iii) The dose (or dose range);
(iv) The intervals between doses, if applicable;
(v) The duration of treatment;
(vi) The maximum volume per injection site, if required to
facilitate the drug's safe and effective use;
(vii) Any modification of the information required in paragraphs
(a)(8)(i) through (vi) of this section that is needed for special
animal populations (e.g., neonatal, reproducing, lactating, geriatric,
or those with specific disease states); and
(viii) Other information regarding dosage and administration, if
required to facilitate the drug's safe and effective use.
(9) ``Contraindications''. All Rx new animal drugs with
contraindications must include the contraindications in this section of
full prescribing information.
(10) ``Warnings and Precautions''. This section of full prescribing
information is required for all approved or conditionally approved Rx
new animal drugs. Include in the following order all applicable
subsections, headings, and information:
(i) ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods''. This subsection of full prescribing information is required
for all new animal drugs approved or conditionally approved for use in
food-producing animals and must include all human food safety warnings,
including milk discard times, withdrawal periods, and residue warning
statements, as applicable. The order of the human food safety warnings
in this subsection of full prescribing information must be as described
in paragraphs (a)(10)(i)(B) through (G) of this section, as applicable.
(A) If there is a residue warning statement(s), this subsection of
full prescribing information must be entitled ``Withdrawal Periods and
Residue Warnings''. If there is no residue warning statement, this
subsection of full prescribing information must be entitled
``Withdrawal Periods''. The title of this subsection and all
information in this subsection of full prescribing information must be
centered and placed entirely within compressed arrows, in accordance
with Sec. 201.404(g)(8). The compressed arrows must be black for
package inserts or a color that clearly contrasts from background
colors for other approved labeling.
(B) If the new animal drug is approved or conditionally approved
for use in food-producing animals excluding female animals that produce
milk for human consumption, include in this subsection of full
prescribing information the withdrawal period(s) followed by any
residue warning statements.
(C) If the new animal drug is approved or conditionally approved
for use in food-producing animals excluding female animals that produce
milk for human consumption and there is no withdrawal period, include
in this subsection of full prescribing information the statement ``No
withdrawal period is required when used according to labeling.'',
followed by any residue warning statements.
(D) If the new animal drug is approved or conditionally approved
for use in female animals that produce milk for human consumption,
include in this subsection of full prescribing information the milk
discard time(s), followed by the withdrawal period(s), followed by any
residue warning statements.
(E) If the new animal drug is approved or conditionally approved
for use in female animals that produce milk for human consumption and
there is a milk discard time(s) but no withdrawal period, include in
this subsection of full prescribing information the milk discard
time(s), followed by the statement ``No withdrawal period is required
when used according to labeling.'', followed by any residue warning
statements.
(F) If the new animal drug is approved or conditionally approved
for use in female animals that produce milk for human consumption and
there is no
[[Page 18322]]
milk discard time but there is a withdrawal period(s), include in this
subsection of full prescribing information the withdrawal period(s),
followed by the statement ``No milk discard time is required when used
according to labeling.'', followed by any residue warning statements.
(G) If the new animal drug is approved or conditionally approved
for use in female animals that produce milk for human consumption and
there is no milk discard time and no withdrawal period, include in this
subsection of full prescribing information the statement ``No milk
discard time and no withdrawal period is required when used according
to labeling.'', followed by any residue warning statements.
(ii) ``User Safety Warnings''. This subsection of full prescribing
information is required for all new animal drugs and must include in
the following order:
(A) ``Not for use in humans. Keep out of reach of children.''
(B) All additional user safety warnings listed in decreasing order
of severity or frequency; and
(C) ``To obtain a Safety Data Sheet(s), contact [insert name of
manufacturer] at [insert manufacturer's telephone number] or [insert
manufacturer's website].''
(iii) ``Animal Safety Warnings and Precautions''. All target animal
safety warnings that identify any serious adverse reaction or potential
hazard to the target animal(s) associated with the use of the new
animal drug and all precautions must be included in this subsection of
full prescribing information. These items must be listed in decreasing
order of severity or frequency.
(iv) ``Environmental Warnings''. All environmental warnings
applicable to the new animal drug that are included in an approved or
conditionally approved application must be provided in this subsection
of full prescribing information.
(v) ``Other Warnings''. Any other required warnings must be
included in this subsection of full prescribing information.
(11) ``Adverse Reactions''. Include in this section of full
prescribing information the adverse reactions, as determined by FDA,
that occur with use of the Rx new animal drug and with use of drugs in
the same pharmacologically active and chemically related class, if
applicable. Include information necessary to interpret the adverse
reactions (e.g., for field studies include total number of animals
exposed, extent and nature of exposure). Within the following
categories, as applicable, present the adverse reactions in decreasing
order of severity or frequency.
(i) ``Pre-approval experience''. Include adverse reactions observed
in laboratory or field studies in the target animal(s).
(ii) ``Foreign market experience''. If the drug product has been
commercially marketed outside the United States, include information
from foreign adverse drug experience reports known prior to U.S.
approval.
(iii) ``Post-approval experience''. Include the adverse reactions
identified from domestic and foreign adverse drug experience reports.
(12) ``Contact Information''. The following statements must be
included in this section of full prescribing information: ``Contact
[insert name of business] at [insert business telephone number] or
[insert business web address]. To report suspected adverse drug
experiences, contact [insert name of business] at [insert business
telephone number]. For additional information about reporting adverse
drug experiences for animal drugs, contact FDA at [insert current FDA
telephone number for voluntary reporting of adverse drug experiences]
or [insert current FDA web address for voluntary reporting of adverse
drug experiences].'' Use as the name of the business the manufacturer,
packer, or distributor identified in the ``Name and place of business''
section of full prescribing information according to paragraph (a)(22)
of this section. If more than one business is identified in the ``Name
and place of business'' section of full prescribing information, select
the most appropriate to identify as the ``business'' in the ``Contact
Information'' section of full prescribing information to provide
additional information about the Rx new animal drug and to contact
regarding suspected adverse drug experiences.
(13) ``Information for Animal Owner''. Any specific information
that FDA determines is necessary for the animal owner or person
treating the animal to use the Rx new animal drug safely and
effectively must be included in this section of full prescribing
information. If FDA requires additional labeling (e.g., a client
information sheet), a printed copy must be attached to, or accompany,
the package insert or secondary container labeling if no package insert
is provided.
(14) ``Clinical Pharmacology''. If required by FDA to facilitate
the drug's safe and effective use, include a summary of the clinical
pharmacology of the Rx new animal drug in the target animal(s) in this
section of full prescribing information, including the following three
subsections, as applicable:
(i) ``Mechanism of action'';
(ii) ``Pharmacodynamics''; and
(iii) ``Pharmacokinetics''.
(15) ``Microbiology''. This section of full prescribing information
is required for all antimicrobial Rx new animal drugs and must include
a description of microbiologic data associated with the studies used to
support the effectiveness of the drug against the indicated pathogens.
Microbiology data must be restricted to organisms named in the approved
or conditionally approved indications. If in vitro data for
antimicrobial new animal drugs are included in this section of full
prescribing information that have not been correlated to clinical
effectiveness, the data must be immediately preceded by the statement:
``The following in vitro data are available, but their clinical
significance is unknown.''
(16) ``Target Animal Safety''. This section of full prescribing
information must include a summary of the basis for the conclusion that
the new animal drug is safe in the target animal(s) when used as
approved or conditionally approved.
(17) ``Effectiveness''. This section of full prescribing
information must include a summary of the basis for the conclusion that
the new animal drug is effective in the target animal(s) when used as
approved. For a conditionally approved new animal drug, include a
summary of the basis for the reasonable expectation of effectiveness.
(18) ``Net Contents''. This section of full prescribing information
must identify the contents of the secondary container. Exclude this
section from package inserts.
(19) ``How Supplied''. This section of full prescribing information
must include information on the available drug strengths,
concentrations, and container sizes to which the labeling applies.
Revise this section of full prescribing information if new strengths,
concentrations, or container sizes are added.
(20) ``Storage, Handling, and Disposal''. This section of full
prescribing information must include drug storage information. Also
include any required handling and drug disposal information in this
section.
(21) NADA/ANADA approval statement. In accordance with section
502(w)(3) of the Federal Food, Drug, and Cosmetic Act, approved new
animal drugs must include the following statement in this section of
full prescribing information: ``Approved by FDA under NADA # xxx-xxx''.
Approved generic new animal drugs must include the following statement
in
[[Page 18323]]
this section of full prescribing information: ``Approved by FDA under
ANADA # xxx-xxx''. This statement must appear in this section of full
prescribing information and:
(i) Appear on one straight line unless there is insufficient space,
in which case the statement may appear on two straight lines;
(ii) Not be incorporated into a seal, stamp, logo or other graphic;
(iii) Be of consistent type size, color, and contrast and be of no
greater prominence than the rest of the labeling text; and
(iv) Not obscure or otherwise render less conspicuous any word,
statement, or other information required by FDA.
(22) Name and place of business. This section of full prescribing
information must include the name and place of business of the
manufacturer, packer, or distributor.
(23) ``Lot Number and Expiration Date''. This section is required
when full prescribing information is provided on the secondary
container labeling. This section must include the identifying lot or
control number of the Rx new animal drug within the secondary
container. This section must also include the expiration date of the Rx
new animal drug within the secondary container, in accordance with
Sec. 201.17. Alternatively, this section must refer to the location on
the secondary container labeling or secondary container where the lot
or control number and expiration date are printed. In accordance with
Sec. 201.17, an expiration date may be excluded from the secondary
container labeling or secondary container if the expiration date
provided on the label or immediate container is easily legible through
the secondary container.
(24) ``Revision Date''. This section of full prescribing
information must include the date of the most recent revision of the
component of labeling that provides full prescribing information,
listing the month followed by the year.
(b) Prescription new animal drug label (Rx label). All approved or
conditionally approved Rx new animal drugs must provide a label (Rx
label). The following information, as applicable, must appear in the
order listed on the Rx label. If there is insufficient space on the
immediate container for a label to provide for all of the following
information, then an Rx small label is required instead. The
requirements for an Rx small label are provided in paragraph (c) of
this section. Section headings and other text presented in quotations
in this paragraph must appear verbatim on the Rx label. Sections are
not numbered on the Rx label. For Rx labels with a front panel and one
side or back panel, the information identified in paragraph (b)(1) of
this section must be provided on the front panel in the order listed,
and the information identified in paragraph (b)(2) of this section must
be provided on the side or back panel in the order listed. If the Rx
label consists of a single panel, the information identified in
paragraph (b)(1) must be provided on the Rx label in the order listed
followed by the information identified in paragraph (b)(2) in the order
listed. For Rx labels with a front panel and multiple side and/or back
panels, the information identified in paragraph (b)(1) must be provided
on the Rx label in the order listed followed by the information
identified in paragraph (b)(2) in the order listed, starting on the
front panel, continuing on the panel immediately to the right of the
front panel, and continuing to fill the panels to the right until all
of the information is presented. In all instances, the information
specified in paragraphs (b)(2)(iii) and (iv) must appear on the same
panel.
(1) Front panel. The following information must appear on the front
panel of the Rx label in the order listed.
(i) Drug product identification. This section of the Rx label must
include:
(A) The proprietary name of the finished drug product;
(B) The established name of the drug product;
(C) The route(s) of administration, if not included as part of the
established name of the drug product;
(D) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(E) The established name and strength or concentration of each
active ingredient;
(F) If applicable, a statement that the product is sterile;
(G) The pharmacological class of the new animal drug, if required
to facilitate the drug's safe and effective use; and
(H) For controlled substances, the required controlled substance
symbol, in accordance with part 1302 of this title designating the
schedule for the drug substance.
(ii) Prescription statement. This section of the Rx label must
include the following statement, in accordance with section 503(f)(4)
of the Federal Food, Drug, and Cosmetic Act: ``Caution: Federal law
restricts this drug to use by or on the order of a licensed
veterinarian.''
(iii) Conditional approval statement. For conditionally approved
new animal drugs, the requirements of paragraph (a)(3) of this section
apply.
(iv) Boxed warnings. For Rx new animal drugs that have boxed
warnings, the requirements of paragraph (a)(4) of this section apply.
(v) ``Indications for Use''. The requirements of paragraph (a)(7)
of this section apply. However, if there is insufficient space on the
Rx label for the complete ``Indications for Use'' section as specified
in paragraph (a)(7), then include the statement required in paragraph
(a)(7)(i) or, if there is insufficient space on the Rx label for the
statement in paragraph (a)(7)(i), then include the statement, ``For
[abbreviated indication(s)] in [target animal(s)]''. In either
situation where there is insufficient space on the Rx label for the
complete ``Indications for Use'' section as specified in paragraph
(a)(7), the required statement must be followed by, ``See package
insert for complete `Indications for Use''' if full prescribing
information is provided on a package insert, or ``See package labeling
for complete `Indications for Use''' if full prescribing information is
provided on the secondary container labeling.
(vi) Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use as listed under Sec. 530.41 of
this chapter, the requirements of paragraph (a)(5) of this section
apply.
(vii) ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods''. For new animal drugs approved or conditionally approved for
use in food-producing animals, the requirements of paragraph (a)(10)(i)
of this section apply. If there is insufficient space on the front
panel of Rx labels consisting of only a front panel and one side or
back panel for the information required in paragraph (a)(10)(i), this
section must be provided on the side or back panel of the Rx label
immediately following the full prescribing information statement
specified in paragraph (b)(2)(i) of this section.
(viii) ``Net Contents''. This section of the Rx label must identify
the contents of the immediate container, in accordance with Sec.
201.5.
(ix) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of paragraph
(a)(21) of this section apply.
(2) Side or back panel. The following information must appear on
the side or back panel of the Rx label in the order listed.
(i) Full prescribing information statement. This section of the Rx
label must include one of two statements. If full prescribing
information is provided
[[Page 18324]]
on the package insert, the following statement must be used: ``Before
using this drug, read package insert for full prescribing
information.'' If full prescribing information is provided on the
secondary container labeling, the following statement must be used:
``Before using this drug, read package labeling for full prescribing
information.''
(ii) ``Dosage and Administration''. The requirements of paragraph
(a)(8) of this section apply. If there is insufficient space on the Rx
label for the complete requirements as specified in paragraph (a)(8) or
if it is necessary for additional information provided in full
prescribing information that is not provided on the Rx label to be read
before administering the drug, FDA may allow this section to be
excluded from the Rx label.
(iii) ``Active Ingredient'' or ``Active Ingredients''. This section
of the Rx label must provide the established name and strength or
concentration of each active ingredient. If the Rx new animal drug
contains one active ingredient, this section of the Rx label must be
entitled ``Active Ingredient''. If the Rx new animal drug contains more
than one active ingredient, this section of the Rx label must be
entitled ``Active Ingredients.''
(iv) ``Inactive Ingredients''. The requirements of paragraph
(a)(6)(viii) of this section apply.
(v) ``Storage, Handling, and Disposal''. The requirements of
paragraph (a)(20) of this section apply.
(vi) Name and place of business. This section of the Rx label must
include the name and place of business of the manufacturer, packer, or
distributor, in accordance with section 502(b) of the Federal Food,
Drug, and Cosmetic Act.
(vii) ``Lot Number and Expiration Date'' or ``Lot Number''. This
section of the Rx label must include the identifying lot or control
number of the Rx new animal drug within the immediate container. This
section of the Rx label must also include the expiration date of the Rx
new animal drug within the immediate container, in accordance with
Sec. 201.17. Alternatively, this section must refer to the location on
the Rx label or immediate container where the lot or control number and
expiration date are printed. In accordance with Sec. 201.17, if the
immediate container provides a single dose of the Rx new animal drug
and is packaged individually in a secondary container that provides an
expiration date on the secondary container labeling or secondary
container, an expiration date is not required on the Rx label or
immediate container. If an expiration date is not provided on the Rx
label or immediate container per this provision, then this section of
the Rx label must be entitled ``Lot Number.''
(viii) ``Revision Date''. This section of the Rx label must include
the date of the most recent revision of the Rx label, listing the month
followed by the year.
(c) Prescription new animal drug small label (Rx small label). The
following information, as applicable, must appear in the order listed
on the Rx small label. FDA will make the final determination as to
whether an immediate container lacks sufficient space for the label to
include all of the information required by paragraph (b) of this
section, taking into consideration readability and legibility of the
information. Section headings and other text presented in quotations in
this paragraph must appear verbatim on the Rx small label. Sections are
not numbered on the Rx small label.
(1) Proprietary name. This section of the Rx small label must
provide the proprietary name of the finished drug product.
(2) Established name. This section of the Rx small label must
provide the established name of the drug product.
(3) Active ingredient(s). This section of the Rx small label must
provide the established name and strength or concentration of each
active ingredient.
(4) Controlled substance symbol. For controlled substances, this
section of the Rx small label must include the required controlled
substance symbol, in accordance with part 1302 of this title
designating the schedule for the drug substance.
(5) Prescription statement. This section of the Rx small label must
include the following: ``Rx Animal Use''.
(6) Target animals. This section of the Rx small label must include
the statement: ``For [target animal(s)] only''.
(7) Full prescribing information statement. This section of the Rx
small label must include one of two statements. If full prescribing
information is provided on the package insert, the following statement
must be used: ``Read package insert for full prescribing information.''
If full prescribing information is provided on the secondary container
labeling, the following statement must be used: ``Read package labeling
for full prescribing information.''
(8) ``Net Contents''. This section of the Rx small label must
identify the contents of the immediate container, in accordance with
Sec. 201.51.
(9) Name and place of business. This section of the Rx small label
must include the name and place of business of the manufacturer,
packer, or distributor, in accordance with section 502(b) of the
Federal Food, Drug, and Cosmetic Act.
(10) ``Lot, Exp. and Storage'' or ``Lot and Storage''. This section
of the Rx small label must include the identifying lot or control
number of the Rx new animal drug within the immediate container. This
section of the Rx small label must also include the expiration date of
the Rx new animal drug within the immediate container, in accordance
with Sec. 201.17. Drug storage information for the Rx new animal drug
must also be included in this section of the Rx small label. In
accordance with Sec. 201.17, if the immediate container provides a
single dose of the Rx new animal drug and is packaged individually in a
secondary container that provides an expiration date on the secondary
container labeling or secondary container, an expiration date is not
required on the Rx small label or immediate container. If an expiration
date is not provided on the Rx small label or immediate container per
this provision, then this section of the Rx small label must be
entitled ``Lot and Storage.''
(11) ``Revision Date''. This section of the Rx small label must
include the date of the most recent revision of the Rx small label,
listing the month followed by the year.
(d) Labeling for secondary containers for Rx new animal drugs that
include a package insert (Rx secondary container labeling). If a
secondary container is provided for an approved or conditionally
approved Rx new animal drug and the Rx new animal drug includes a
package insert, the following information, as applicable, must appear
in the order listed on the secondary container labeling (Rx secondary
container labeling). In accordance with section 201(k) of the Federal
Food, Drug, and Cosmetic Act, the Rx secondary container labeling may
exclude any of the information described in this subsection that is
required by paragraphs (b) or (c) of this section to appear on the
label if such information is easily legible through the Rx secondary
container. Section headings, subsection headings, and other text
presented in quotations in this paragraph must appear verbatim on the
Rx secondary container labeling. Sections and subsections are not
numbered on the Rx secondary container labeling. For Rx secondary
container labeling with a front panel and one side or back panel, the
information identified in paragraph (d)(1) of this section must be
provided on the front panel in the order listed, and the information
identified in
[[Page 18325]]
paragraph (d)(2) of this section must be provided on the side or back
panel in the order listed. For Rx secondary container labeling with a
front panel and multiple side and/or back panels, the information
identified in paragraph (d)(1) must be provided on the Rx secondary
container labeling in the order listed followed by the information
identified in paragraph (d)(2) in the order listed, starting on the
front panel, continuing on the panel immediately to the right of the
front panel, and continuing to fill the panels to the right until all
of the information is presented. In all instances, the information
specified in paragraphs (d)(2)(v) and (vi) of this section must appear
on the same panel.
(1) Front panel. The following information must appear on the front
panel of the Rx secondary container labeling in the order listed.
(i) Drug product identification. This section of the Rx secondary
container labeling must include:
(A) The proprietary name of the finished drug product;
(B) The established name of the drug product;
(C) The route(s) of administration, if not included as part of the
established name of the drug product;
(D) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(E) The established name and strength or concentration of each
active ingredient;
(F) If applicable, a statement that the product is sterile;
(G) The pharmacological class of the new animal drug, if required
to facilitate the drug's safe and effective use; and
(H) For controlled substances, the required controlled substance
symbol, in accordance with part 1302 of this title designating the
schedule for the drug substance.
(ii) Prescription statement. The requirements of paragraph (a)(2)
of this section apply.
(iii) Conditional approval statement. The requirements of paragraph
(a)(3) of this section apply.
(iv) Boxed warnings. The requirements of paragraph (a)(4) of this
section apply.
(v) ``Indications for Use''. The requirements of paragraph (a)(7)
of this section apply.
(vi) Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use as listed under Sec. 530.41 of
this chapter, the requirements of paragraph (a)(5) of this section
apply.
(vii) ``Net Contents''. This section of the Rx secondary container
labeling must identify the contents of the secondary container.
(viii) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of paragraph
(a)(21) of this section apply.
(2) Side or back panel. The following information must appear on
the side or back panel of the Rx secondary container labeling in the
order listed.
(i) Full prescribing information statement. This section of the Rx
secondary container labeling must include the following statement:
``Before using this drug, read package insert for full prescribing
information.''
(ii) ``Dosage and Administration''. The requirements of paragraph
(a)(8) of this section apply.
(iii) ``Contraindications''. The requirements of paragraph (a)(9)
of this section apply.
(iv) ``Warnings and Precautions''. The requirements of paragraph
(a)(10) of this section apply.
(v) ``Active Ingredient'' or ``Active Ingredients''. The
requirements of paragraph (b)(2)(iii) of this section apply.
(vi) ``Inactive Ingredients''. The requirements of paragraph
(a)(6)(viii) of this section apply.
(vii) ``Storage, Handling, and Disposal''. The requirements of
paragraph (a)(20) of this section apply.
(viii) Name and place of business. The requirements of paragraph
(a)(22) of this section apply.
(ix) ``Lot Number and Expiration Date''. This section of the Rx
secondary container labeling must include the identifying lot or
control number of the Rx new animal drug within the secondary
container. This section of the Rx secondary container labeling must
also include the expiration date of the Rx new animal drug within the
secondary container, in accordance with Sec. 201.17. Alternatively,
this section must refer to the location on the Rx secondary container
labeling or secondary container where the lot or control number and
expiration date are printed. In accordance with Sec. 201.17, an
expiration date may be excluded from the Rx secondary container
labeling or secondary container if the expiration date provided on the
Rx label, Rx small label, or immediate container is easily legible
through the secondary container.
(x) ``Revision Date''. This section of the Rx secondary container
labeling must include the date of the most recent version of the Rx
secondary container labeling, listing the month followed by the year.
(e) Shipping labeling for Rx new animal drugs (Rx shipping
labeling). If shipping labeling is provided for an approved or
conditionally approved Rx new animal drug (Rx shipping labeling), the
following information, as applicable, must appear in the order listed
on the Rx shipping labeling. Section headings and other text presented
in quotations in this paragraph must appear verbatim on the Rx shipping
labeling. Sections are not numbered on the Rx shipping labeling.
(1) Proprietary name. This section of the Rx shipping labeling must
provide the proprietary name of the finished drug product, unless the
Rx new animal drug is a controlled substance.
(2) Established name. This section of the Rx shipping labeling must
provide the established name of the drug product, unless the Rx new
animal drug is a controlled substance.
(3) Active ingredient(s). This section of the Rx shipping labeling
must provide the established name and strength or concentration of each
active ingredient, unless the Rx new animal drug is a controlled
substance.
(4) Conditional approval statement. The requirements of paragraph
(a)(3) of this section apply, unless the Rx new animal drug is a
controlled substance.
(5) ``Net Contents''. This section of the Rx shipping labeling must
identify the contents of the shipping carton.
(6) ``Storage and Handling''. This section of the Rx shipping
labeling must include drug storage information. If required by FDA to
facilitate the drug's safe and effective use, also include handling
information.
(7) NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the requirements of paragraph
(a)(21) of this section apply, unless the Rx new animal drug is a
controlled substance.
(8) Name and place of business. The requirements of paragraph
(a)(22) of this section apply.
(9) ``Lot Number and Expiration Date''. This section of the Rx
shipping labeling must include the identifying lot or control number(s)
and the expiration date(s) of the Rx new animal drug within the
shipping carton.
(10) ``Revision Date''. This section of the Rx shipping labeling
must include the date of the most recent revision of the Rx shipping
labeling, listing the month followed by the year.
(f) Other approved labeling for Rx new animal drugs (Rx other
approved labeling). If other approved labeling is provided for an
approved or conditionally approved Rx new animal drug (Rx other
approved labeling), such as labeling on display cartons and multi-unit
cartons (excluding shipping
[[Page 18326]]
cartons), the following information, as applicable, must appear in the
order listed on the Rx other approved labeling. Section headings and
other text presented in quotations in this paragraph must appear
verbatim on the Rx other approved labeling. Sections are not numbered
on the Rx other approved labeling.
(1) Proprietary name. This section of the Rx other approved
labeling must provide the proprietary name of the finished drug
product.
(2) Established Name. This section of the Rx other approved
labeling must provide the established name of the drug product.
(3) Active ingredient(s). This section of the Rx other approved
labeling must provide the established name and strength or
concentration of each active ingredient.
(4) Controlled substance symbol. For controlled substances, this
section of the Rx other approved labeling must include the required
controlled substance symbol, in accordance with part 1302 of this title
designating the schedule for the drug substance.
(5) Prescription statement. The requirements of paragraph (a)(2) of
this section apply.
(6) Conditional approval statement. The requirements of paragraph
(a)(3) of this section apply.
(7) Boxed warnings. The requirements of paragraph (a)(4) of this
section apply.
(8) Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use as listed under Sec. 530.41 of
this chapter, the requirements of paragraph (a)(5) of this section
apply.
(9) ``Net Contents''. This section of the Rx other approved
labeling must identify the contents of the container to which the Rx
other approved labeling applies.
(10) ``Storage, Handling, and Disposal''. The requirements of
paragraph (a)(20) of this section apply.
(11) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of paragraph
(a)(21) of this section apply.
(12) Name and place of business. The requirements of paragraph
(a)(22) of this section apply.
(13) ``Lot Number and Expiration Date''. This section of the Rx
other approved labeling must include the identifying lot or control
number of the Rx new animal drug within the container to which the Rx
other approved labeling applies. This section of the Rx other approved
labeling must also include the expiration date of the Rx new animal
drug within the container to which the Rx other approved labeling
applies. In accordance with Sec. 201.17, an expiration date may be
excluded from the Rx other approved labeling if the expiration date
provided on containers within or their labeling is easily legible
through the container to which the Rx other approved labeling applies.
(14) ``Revision Date''. This section of the Rx other approved
labeling must include the date of the most recent revision of the Rx
other approved labeling, listing the month followed by the year.
Sec. 201.407 Content and format for over-the-counter (OTC) new
animal drug labeling.
This section describes specific content and format requirements for
the labeling of approved or conditionally approved OTC new animal drugs
other than those for use in animal feeds that are subject to part 558
of this chapter. See Sec. 201.409 for content and format requirements
for the labeling of approved or conditionally approved new animal drugs
for use in animal feeds that are subject to part 558 of this chapter.
Omit labeling sections or subsections that do not apply to the OTC new
animal drug. The final content of each applicable component and section
of labeling is determined by FDA. In addition to the content and format
requirements in this section, the labeling of approved or conditionally
approved OTC new animal drugs must comply with other applicable
requirements in this subpart.
(a) Labeling providing full product information. All approved or
conditionally approved OTC new animal drugs must provide full product
information as described in this paragraph. The package insert must
include full product information. If no package insert is provided, the
secondary container labeling must include full product information as
described in this paragraph. If neither a package insert nor a
secondary container is provided, the label must include full product
information as described in this paragraph. The following information,
as applicable, must appear in the order listed on the labeling
component providing full product information. If full product
information is provided on the secondary container labeling, in
accordance with section 201(k) of the Federal Food, Drug, and Cosmetic
Act, the secondary container labeling may exclude any of the
information described in this subsection that is required by paragraphs
(b) or (c) of this section to appear on the label if such information
is easily legible through the secondary container. Section headings,
subsection headings, and other text presented in quotations in this
paragraph must appear verbatim on the labeling providing full product
information. Sections and subsections are not numbered on full product
information.
(1) Drug product identification. This section of full product
information must include:
(i) The proprietary name of the finished drug product;
(ii) The established name of the drug product;
(iii) The route(s) of administration, if not included as part of
the established name of the drug product;
(iv) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(v) The established name and strength or concentration of each
active ingredient, except that the strength or concentration may be
excluded from full product information provided on a package insert
that applies to multiple strengths or concentrations; and
(vi) The pharmacological class of the new animal drug, if required
to facilitate the drug's safe and effective use.
(2) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(3) ``Uses''. Include the following information in this section of
full product information in order:
(i) The approved or conditionally approved indication(s) and target
animal(s) in the following format: ``For [indication(s)] in [target
animal(s)]'';
(ii) A statement indicating that the new animal drug is approved or
conditionally approved for use only under specific conditions, if
applicable;
(iii) A statement describing the relative effectiveness of doses
within the approved range of doses, if required by FDA to facilitate
the drug's safe and effective use; and
(iv) A statement(s) indicating animals for which the new animal
drug is not approved or conditionally approved, if FDA determines such
a statement(s) is required for safety and/or effectiveness reasons.
(4) Extralabel use statement. This section of full product
information must include the following extralabel use statement: ``It
is a violation of Federal law to use this drug product other than as
directed in the labeling or as directed by your veterinarian.''
(5) Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use as listed under Sec. 530.41 of
this chapter, the requirements of Sec. 201.405(a)(5) apply.
[[Page 18327]]
(6) ``Description''. This section of full product information must
include:
(i) The proprietary name of the finished drug product;
(ii) The established name of the drug product;
(iii) The route(s) of administration, if not included as part of
the established name of the drug product;
(iv) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(v) A description of the identifying characteristics of the dosage
form, such as color, shape, coating, scoring, and imprinting;
(vi) The established name and strength or concentration of each
active ingredient, including all available strengths or concentrations
to which full product information applies;
(vii) If applicable, a statement that the product is sterile; and
(viii) When inactive ingredients are provided on full product
information, the requirements of Sec. 201.405(a)(6)(viii) apply.
(7) ``Warnings''. This section of full product information is
required for all approved or conditionally approved new animal drugs.
Include in the following order all applicable subsections, headings,
and information:
(i) ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods''. The requirements of Sec. 201.405(a)(10)(i) apply.
(ii) ``User Safety Warnings''. The requirements of Sec.
201.405(a)(10)(ii) apply.
(iii) ``Animal Safety Warnings''. All contraindications, target
animal safety warnings that identify any serious adverse reaction or
potential hazard to the target animal(s) associated with the use of the
new animal drug, adverse reactions, and post-approval adverse drug
experiences must be included in this subsection of full product
information. These items must be listed in decreasing order of severity
or frequency.
(iv) ``Environmental Warnings''. The requirements of Sec.
201.405(a)(10)(iv) apply.
(v) ``Other Warnings''. The requirements of Sec. 201.405(a)(10)(v)
apply.
(8) ``Additional Recommendations''. This section of full product
information must include all precautions.
(9) ``Other Effects You May Notice''. This section of full product
information must include all statements required by FDA that identify
any effects of the OTC new animal drug on the target animal(s) that are
not considered contraindications, target animal safety warnings,
adverse reactions, or post-approval adverse drug experiences.
(10) ``Directions''. This section of full product information must
include for each indication and target animal:
(i) The route(s) of administration, and specific site(s) of
administration, if applicable;
(ii) The dose (or dose range);
(iii) The intervals between doses, if applicable;
(iv) The duration of treatment;
(v) The maximum volume per injection site, if required to
facilitate the drug's safe and effective use; and
(vi) Other information regarding administration, if required by FDA
to facilitate the drug's safe and effective use.
(11) ``Net Contents''. This section of full product information,
when presented on the label or the secondary container labeling, must
identify the contents of the immediate container, in accordance with
Sec. 201.62, or the secondary container, respectively. Exclude this
section from package inserts.
(12) ``How Supplied''. The requirements of Sec. 201.405(a)(19)
apply.
(13) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(14) ``Questions/Comments?''. The following statements must be
included in this section of full product information: ``Contact [insert
name of business] at [insert business telephone number] or [insert
business web address]. To report side effects, contact [insert name of
business] at [insert business telephone number]. For additional
information about reporting side effects for animal drugs, contact FDA
at [insert current FDA telephone number for voluntary reporting of
adverse drug experiences] or [insert current FDA web address for
voluntary reporting of adverse drug experiences].'' Use as the name of
the business the manufacturer, packer, or distributor identified in the
``Name and place of business'' section of full product information
according to paragraph (a)(16) of this section. If more than one
business is identified in the ``Name and place of business'' section of
full product information, select the most appropriate to identify as
the ``business'' in the ``Questions/Comments?'' section of full product
information to provide additional information about the OTC new animal
drug and to contact regarding suspected adverse drug experiences.
(15) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(16) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(17) ``Lot Number and Expiration Date''. This section is required
when full product information is provided on the secondary container
labeling or the label. This section must include the identifying lot or
control number of the OTC new animal drug within the secondary
container or immediate container. This section must also include the
expiration date of the OTC new animal drug within the secondary
container or immediate container, in accordance with Sec. 201.17.
Alternatively, this section must refer to the location on the secondary
container labeling, secondary container, label, or immediate container
where the lot or control number and expiration date are printed. If
full product information is provided on the secondary container
labeling, in accordance with Sec. 201.17, an expiration date may be
excluded from the secondary container labeling or secondary container
if the expiration date provided on the label or immediate container is
easily legible through the secondary container.
(18) ``Revision Date''. This section of full product information
must include the date of the most recent revision of the component of
labeling that provides full product information, listing the month
followed by the year.
(b) OTC new animal drug label not providing full product
information (OTC label). All approved or conditionally approved OTC new
animal drugs must provide a label. If a package insert or secondary
container labeling with full product information is provided for an
approved or conditionally approved OTC new animal drug and the label
does not provide full product information in accordance with paragraph
(a) of this section, the following information, as applicable, must
appear in the order listed on the label for approved or conditionally
approved OTC new animal drugs (OTC label). If there is insufficient
space on the immediate container for a label to provide for all of the
following information, then an OTC small label is required instead. The
requirements for an OTC small label are provided in paragraph (c) of
this section. Section headings and other text presented in quotations
in this paragraph must appear verbatim on the OTC label. Sections are
not numbered on the OTC label. For OTC labels with a front panel and
one side or back panel, the information identified in paragraph (b)(1)
of this section must be provided on the front panel in the order
listed,
[[Page 18328]]
and the information identified in paragraph (b)(2) of this section must
be provided on the side or back panel in the order listed. If the OTC
label consists of a single panel, the information identified in
paragraph (b)(1) of this section must be provided on the OTC label in
the order listed followed by the information identified in paragraph
(b)(2) in the order listed. For OTC labels with a front panel and
multiple side and/or back panels, the information identified in
paragraph (b)(1) must be provided on the OTC label in the order listed
followed by the information identified in paragraph (b)(2) in the order
listed, starting on the front panel, continuing on the panel
immediately to the right of the front panel, and continuing to fill the
panels to the right until all of the information is presented. In all
instances, the information specified in paragraphs (b)(2)(iii) and (iv)
of this section must appear on the same panel.
(1) Front panel. The following information must appear on the front
panel of the OTC label in the order listed.
(i) Drug product identification. This section of the OTC label must
include:
(A) The proprietary name of the finished drug product;
(B) The established name of the drug product;
(C) The route(s) of administration, if not included as part of the
established name of the drug product;
(D) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(E) The established name and strength or concentration of each
active ingredient;
(F) If applicable, a statement that the product is sterile; and
(G) The pharmacological class of the new animal drug, if required
to facilitate the drug's safe and effective use.
(ii) Conditional approval statement. For conditionally approved new
animal drugs, the requirements of Sec. 201.405(a)(3) apply.
(iii) ``Uses''. The requirements of paragraph (a)(3) of this
section apply. However, if there is insufficient space on the OTC label
for the complete ``Uses'' section as specified in paragraph (a)(3),
then include the statement required in paragraph (a)(3)(i) or, if there
is insufficient space on the OTC label for the statement in paragraph
(a)(3)(i), then include the statement, ``For [abbreviated
indication(s)] in [target animal(s)]''). In either situation where
there is insufficient space on the OTC label for the complete ``Uses''
section as specified in paragraph (a)(3), the required statement must
be followed by, ``See package insert for complete `Uses' '' if full
product information is provided on a package insert, or ``See package
labeling for complete `Uses' '' if full product information is provided
on the secondary container labeling.
(iv) Extralabel use statement. The requirements of paragraph (a)(4)
of this section apply.
(v) Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use as listed under Sec. 530.41 of
this chapter, the requirements of Sec. 201.405(a)(5) apply.
(vi) ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods''. For new animal drugs approved or conditionally approved for
use in food-producing animals, the requirements of Sec.
201.405(a)(10)(i) apply. If there is insufficient space on the front
panel of OTC labels consisting of only a front panel and one side or
back panel for the information required in Sec. 201.405(a)(10)(i),
this section must be provided on the side or back panel of the OTC
label immediately following the complete product information statement
specified in paragraph (b)(2)(i) of this section.
(vii) ``Net Contents''. This section of the OTC label must identify
the contents of the immediate container, in accordance with Sec.
201.62.
(viii) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(2) Side or back panel. The following information must appear on
the side or back panel of the OTC label in the order listed.
(i) Complete product information statement. This section of the OTC
label must include one of two statements. If full product information
is provided on the package insert, the following statement must be
used: ``Before using this drug, read package insert for complete
product information.'' If full product information is provided on the
secondary container labeling, the following statement must be used:
``Before using this drug, read package labeling for complete product
information.''
(ii) ``Directions''. The requirements of paragraph (a)(10) of this
section apply. If there is insufficient space on the OTC label for
complete requirements as specified in paragraph (a)(10) of this section
or if it is necessary for additional information provided in full
product information that is not provided on the OTC label to be read
before administering the drug, FDA may allow this section to be
excluded from the OTC label.
(iii) ``Active Ingredient'' or ``Active Ingredients''. This section
of the OTC label must provide the established name and strength or
concentration of each active ingredient. If the OTC new animal drug
contains one active ingredient, this section of the OTC label must be
entitled ``Active Ingredient''. If the OTC new animal drug contains
more than one active ingredient, this section of the OTC label must be
entitled ``Active Ingredients.''
(iv) ``Inactive Ingredients''. When inactive ingredients are
provided on the OTC label, the requirements of Sec.
201.405(a)(6)(viii) apply.
(v) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(vi) Name and place of business. This section of the OTC label must
include the name and place of business of the manufacturer, packer, or
distributor, in accordance with section 502(b) of the Federal Food,
Drug, and Cosmetic Act.
(vii) ``Lot Number and Expiration Date'' or ``Lot Number''. This
section of the OTC label must include the identifying lot or control
number of the OTC new animal drug within the immediate container. This
section of the OTC label must also include the expiration date of the
OTC new animal drug within the immediate container, in accordance with
Sec. 201.17. Alternatively, this section must refer to the location on
the OTC label or immediate container where the lot or control number
and expiration date are printed. In accordance with Sec. 201.17, if
the immediate container provides a single dose of the OTC new animal
drug and is packaged individually in a secondary container that
provides an expiration date on the secondary container labeling or
secondary container, an expiration date is not required on the OTC
label or immediate container. If an expiration date is not provided on
the OTC label or immediate container per this provision, then this
section of the OTC label must be titled ``Lot Number.''
(viii) ``Revision Date''. This section of the OTC label must
include the date of the most recent revision of the OTC label, listing
the month followed by the year.
(c) OTC new animal drug small label (OTC small label). The
following information must appear in the order listed on the OTC small
label. FDA will make the final determination as to whether an immediate
container lacks sufficient space for the label to include all of the
information required by paragraph (b) of this section, taking into
consideration readability and legibility
[[Page 18329]]
of the information. Section headings and other text presented in
quotations in this paragraph must appear verbatim on the OTC small
label. Sections are not numbered on the OTC small label.
(1) Proprietary name. This section of the OTC small label must
provide the proprietary name of the finished drug product.
(2) Established name. This section of the OTC small label must
provide the established name of the drug product.
(3) Active ingredient(s). This section of the OTC small label must
provide the established name and strength or concentration of each
active ingredient.
(4) Target animals. This section of the OTC small label must
include the statement: ``For [target animal(s)] only.''
(5) Complete product information statement. This section of the OTC
small label must include one of two statements. If full product
information is provided on the package insert, the following statement
must be used: ``Read package insert for complete product information.''
If full product information is provided on the secondary container
labeling, the following statement must be used: ``Read package labeling
for complete product information.''
(6) ``Net Contents''. This section of the OTC small label must
identify the contents of the immediate container, in accordance with
Sec. 201.62.
(7) Name and place of business. This section of the OTC small label
must include the name and place of business of the manufacturer,
packer, or distributor, in accordance with section 502(b) of the
Federal Food, Drug, and Cosmetic Act.
(8) ``Lot, Exp. and Storage'' or ``Lot and Storage''. This section
of the OTC small label must include the identifying lot or control
number of the OTC new animal drug within the immediate container. This
section of the OTC small label must also include the expiration date of
the OTC new animal drugs within the immediate container, in accordance
with Sec. 201.17. Drug storage information for the OTC new animal drug
must also be included in this section of the OTC small label. In
accordance with Sec. 201.17, if the immediate container provides a
single dose of the OTC new animal drug and is packaged individually in
a secondary container that provides an expiration date on the secondary
container labeling or secondary container, an expiration date is not
required on the OTC small label or immediate container. If an
expiration date is not provided on the OTC small label or immediate
container per this provision, then this section of the OTC small label
must be entitled ``Lot and Storage.''
(9) ``Revision Date''. This section of the OTC small label must
include the date of the most recent revision of the OTC small label,
listing the month followed by the year.
(d) Labeling for secondary containers for OTC new animal drugs that
include a package insert (OTC secondary container labeling). If a
secondary container is provided for an approved or conditionally
approved OTC new animal drug and the OTC new animal drug includes a
package insert, the following information, as applicable, must appear
in the order listed on the secondary container labeling (OTC secondary
container labeling). In accordance with section 201(k) of the Federal
Food, Drug, and Cosmetic Act, the OTC secondary container labeling may
exclude any of the information described in this subsection that is
required by paragraphs (b) or (c) of this section to appear on the
label if such information is easily legible through the OTC secondary
container. Section headings, subsection headings, and other text
presented in quotations in this paragraph must appear verbatim on the
OTC secondary container labeling. Sections and subsections are not
numbered on the OTC secondary container labeling. For OTC secondary
container labeling with a front panel and one side or back panel, the
information identified in paragraph (d)(1) of this section must be
provided on the front panel in the order listed, and the information
identified in paragraph (d)(2) of this section must be provided on the
side or back panel in the order listed. For OTC secondary container
labeling with a front panel and multiple side and/or back panels, the
information identified in paragraph (d)(1) of this section must be
provided on the OTC secondary container labeling in the order listed
followed by the information identified in paragraph (d)(2) of this
section in the order listed, starting on the front panel, continuing on
the panel immediately to the right of the front panel, and continuing
to fill the panels to the right until all of the information is
presented. In all instances, the information specified in paragraphs
(d)(2)(iv) and (v) of this section must appear on the same panel.
(1) Front panel. The following information must appear on the front
panel of the OTC secondary container labeling in the order listed.
(i) Drug product identification. This section of the OTC secondary
container labeling must include:
(A) The proprietary name of the finished drug product;
(B) The established name of the drug product;
(C) The route(s) of administration, if not included as part of the
established name of the drug product;
(D) The dosage form of the finished drug product, if not included
as part of the established name of the drug product;
(E) The established name and strength or concentration of each
active ingredient;
(F) If applicable, a statement that the product is sterile; and
(G) The pharmacological class of the new animal drug, if required
to facilitate the drug's safe and effective use.
(ii) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(iii) ``Uses''. The requirements of paragraph (a)(3) of this
section apply.
(iv) Extralabel use statement. The requirements of paragraph (a)(4)
of this section apply.
(v) Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use as listed under Sec. 530.41 of
this chapter, the requirements of Sec. 201.405(a)(5) apply.
(vi) ``Net Contents''. This section of the OTC secondary container
labeling must identify the contents of the secondary container.
(vii) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(2) Side or back panel. The following information must appear on
the side or back panel of the OTC secondary container labeling in the
order listed.
(i) Complete product information statement. This section of the OTC
secondary container labeling must include the following statement:
``Before using this drug, read package insert for complete product
information.''
(ii) ``Directions''. The requirements of paragraph (a)(10) of this
section apply.
(iii) ``Warnings''. The requirements of paragraph (a)(7) of this
section apply.
(iv) ``Active Ingredient'' or ``Active Ingredients''. The
requirements of paragraph (b)(2)(iii) of this section apply.
(v) ``Inactive Ingredients''. When inactive ingredients are
provided on the OTC secondary container labeling, the requirements of
Sec. 201.405(a)(6)(viii) apply.
(vi) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(vii) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(viii) ``Lot Number and Expiration Date''. This section of the OTC
[[Page 18330]]
secondary container labeling must include the identifying lot or
control number of the OTC new animal drug within the secondary
container. This section of the OTC secondary container labeling must
also include the expiration date of the OTC new animal drug within the
secondary container, in accordance with Sec. 201.17. Alternatively,
this section must refer to the location on the OTC secondary container
labeling or secondary container where the lot or control number and
expiration date are printed. In accordance with Sec. 201.17, an
expiration date may be excluded from the OTC secondary container
labeling or secondary container if the expiration date provided on the
OTC label, OTC small label, or immediate container is easily legible
through the secondary container.
(ix) ``Revision Date''. This section of the OTC secondary container
labeling must include the date of the most recent revision of the OTC
secondary container labeling, listing the month followed by the year.
(e) Shipping labeling for OTC new animal drugs (OTC shipping
labeling). If shipping labeling is provided for an approved or
conditionally approved OTC new animal drug (OTC shipping labeling), the
following information, as applicable, must appear in the order listed
on the OTC shipping labeling. Section headings and other text presented
in quotations in this paragraph must appear verbatim on the OTC
shipping labeling. Sections are not numbered on the OTC shipping
labeling.
(1) Proprietary name. This section of the OTC shipping labeling
must provide the proprietary name of the finished drug product.
(2) Established name. This section of the OTC shipping labeling
must provide the established name of the drug product.
(3) Active ingredient(s). This section of the OTC shipping labeling
must provide the established name and strength or concentration of each
active ingredient.
(4) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(5) ``Net Contents''. This section of the OTC shipping labeling
must identify the contents of the shipping carton.
(6) ``Storage and Handling''. This section of the OTC shipping
labeling must include drug storage information. If required by FDA to
facilitate the drug's safe and effective use, also include handling
information.
(7) NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(8) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(9) ``Lot Number and Expiration Date''. This section of the OTC
shipping labeling must include the identifying lot or control number(s)
and the expiration date(s) of the OTC new animal drug within the
shipping carton.
(10) ``Revision Date''. This section of the OTC shipping labeling
must include the date of the most recent revision of OTC shipping
labeling, listing the month followed by the year.
(f) Other approved labeling for OTC new animal drugs (OTC other
approved labeling). If other approved labeling is provided for an
approved or conditionally approved OTC new animal drug (OTC other
approved labeling), such as labeling on display cartons and multi-unit
cartons (excluding shipping cartons), the following information, as
applicable, must appear in the order listed on the OTC other approved
labeling. Section headings and other text presented in quotations in
this paragraph must appear verbatim on the OTC other approved labeling.
Sections are not numbered on the OTC other approved labeling.
(1) Proprietary name. This section of the OTC other approved
labeling must provide the proprietary name of the finished drug
product.
(2) Established name. This section of the OTC other approved
labeling must provide the established name of the drug product.
(3) Active ingredient(s). This section of the OTC other approved
labeling must provide the established name and strength or
concentration of each active ingredient.
(4) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(5) Extralabel use statement. The requirements of paragraph (a)(4)
of this section apply.
(6) Extralabel use prohibition statement. For approved new animal
drugs prohibited from extralabel use as listed under Sec. 530.41 of
this chapter, the requirements of Sec. 201.405(a)(5) apply.
(7) ``Net Contents''. This section of the OTC other approved
labeling must identify the contents of the container to which the OTC
other approved labeling applies.
(8) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(9) NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(10) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(11) ``Lot Number and Expiration Date''. This section of the OTC
other approved labeling must include the identifying lot or control
number of the OTC new animal drug within the container to which the OTC
other approved labeling applies. This section of the OTC other approved
labeling must also include the expiration date of the OTC new animal
drug within the container to which the OTC other approved labeling
applies. In accordance with Sec. 201.17, an expiration date may be
excluded from the OTC other approved labeling if the expiration date on
containers within or their labeling is easily legible through the
container to which the OTC other approved labeling applies.
(12) ``Revision Date''. This section of the OTC other approved
labeling must include the date of the most recent revision of the OTC
other approved labeling, listing the month followed by the year.
Sec. 201.409 Content and format of labeling for new animal drugs for
use in animal feeds.
This section describes specific content and format requirements for
the labeling of approved or conditionally approved new animal drugs for
use in animal feeds and that are subject to part 558 of this chapter,
including VFD drugs. Omit labeling sections or subsections that do not
apply to the new animal drug for use in animal feeds. The final content
of each applicable component and section of labeling is determined by
FDA. In addition to the content and format requirements in this
section, the labeling of approved or conditionally approved new animal
drugs for use in animal feeds and that are subject to part 558 of this
chapter must comply with other applicable requirements in this subpart.
(a) Type A medicated article label. All approved or conditionally
approved Type A medicated articles must provide a Type A medicated
article label as described in this paragraph. The following
information, as applicable, must appear in the order listed on the Type
A medicated article label. Section headings, subsection headings, and
other text presented in quotations in this paragraph must appear
verbatim on the Type A medicated article label. Sections and
subsections are not numbered on the Type A medicated article label.
(1) Type A medicated article identification. This section of the
Type
[[Page 18331]]
A medicated article label must include in order:
(i) The proprietary name of the Type A medicated article;
(ii) The established name of the Type A medicated article; and
(iii) The phrase ``Type A medicated article'' or ``Type A liquid
medicated article,'' as applicable, if not included as part of the
established name of the Type A medicated article.
(2) VFD cautionary statement. For VFD drugs, this section of the
Type A medicated article label must prominently and conspicuously
display the cautionary statement, in accordance with Sec. 558.6(a)(6)
of this chapter.
(3) Manufacturing statement. This section of the Type A medicated
article label must include the statement: ``For further manufacturing
only.''
(4) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(5) ``Indications for Use''. The requirements of Sec.
201.407(a)(3) apply.
(6) Extralabel use statement. This section of the Type A medicated
article label must include the following extralabel use statement: ``It
is a violation of Federal law to use other than as directed in the
labeling.''
(7) ``Active Ingredient'' or ``Active Ingredients''. This section
of the Type A medicated article label must provide the established name
and concentration of each active ingredient in the Type A medicated
article. If the Type A medicated article contains one active
ingredient, this section of the Type A medicated article label must be
entitled ``Active Ingredient.'' If the Type A medicated article
contains more than one active ingredient, this section of the Type A
medicated article label must be entitled ``Active Ingredients.''
(8) ``Inactive Ingredients''. When inactive ingredients are
provided on the Type A medicated article label, the requirements of
Sec. 201.405(a)(6)(viii) apply.
(9) ``Directions''. This section of the Type A medicated article
label must include the following three subsections in order:
(i) ``Approved Concentration(s) of [Active Ingredient or Active
Moiety] in Type C Medicated Feeds''. This subsection of the Type A
medicated article label must provide the approved concentration(s) of
each active ingredient in Type C medicated feeds to be manufactured
from the Type A medicated article for each approved or conditionally
approved indications for use. If an active ingredient is a salt or
other noncovalent derivative and its concentration(s) in paragraph
(a)(7) of this section is expressed based on the active moiety, the
approved concentration(s) in the Type C medicated feeds must be
expressed based on the active moiety, and the title of this subsection
must include the name of the active moiety instead of the active
ingredient.
(ii) ``Mixing Directions''. This subsection of the Type A medicated
article label must provide the approved mixing directions for the
manufacture of approved medicated feeds from this Type A medicated
article for each approved or conditionally approved indications for
use, including an intermediate mixing step (i.e., preblend step) if
required.
(iii) ``Feeding Directions''. This subsection of the Type A
medicated article label must provide the approved feeding directions
for each approved or conditionally approved indications for use for
Type C medicated feeds manufactured from this Type A medicated article.
(10) ``Warnings''. This section of the Type A medicated article
label is required for all Type A medicated articles. Include in the
following order all applicable subsections, headings, and information:
(i) ``Withdrawal Periods and Residue Warnings'' or ``Withdrawal
Periods''. The requirements of Sec. 201.405(a)(10)(i) apply.
(ii) ``User Safety Warnings''. The requirements of Sec.
201.405(a)(10)(ii) apply.
(iii) ``Animal Safety Warnings''. The requirements of Sec.
201.407(a)(7)(iii) apply.
(iv) ``Environmental Warnings''. The requirements of Sec.
201.405(a)(10)(iv) apply.
(v) ``Other Warnings''. The requirements of Sec. 201.405(a)(10)(v)
apply.
(11) ``Additional Recommendations''. The requirements of Sec.
201.407(a)(8) apply.
(12) ``Other Effects You May Notice''. The requirements of Sec.
201.407(a)(9) apply.
(13) ``Net Weight''. This section of the Type A medicated article
label must list the net weight of the Type A medicated article in the
immediate container.
(14) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(15) ``Questions/Comments?''. The following statements must be
included in this section of the Type A medicated article label:
``Contact [insert name of business] at [insert business telephone
number] or [insert business web address]. To report side effects,
contact [insert name of business] at [insert business telephone
number]. For additional information about reporting side effects for
animal drugs, contact FDA at [insert current FDA telephone number for
voluntary reporting of adverse drug experiences] or [insert current FDA
web address for voluntary reporting of adverse drug experiences].'' Use
as the name of the business the manufacturer, packer, or distributor
identified in the ``Name and place of business'' section of the Type A
medicated article label according to paragraph (a)(17) of this section.
If more than one business is identified in the ``Name and place of
business'' section of the Type A medicated article label, select the
most appropriate to identify as the ``business'' in the ``Questions/
Comments?'' section of the Type A medicated article label to provide
additional information about the Type A medicated article and to
contact regarding suspected adverse drug experiences.
(16) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(17) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(18) ``Lot Number and Expiration Date''. This section of the Type A
medicated article label must include the identifying lot or control
number of the Type A medicated article within the immediate container.
In accordance with Sec. 226.58(d) of this chapter, this section of the
Type A medicated article label must also include the expiration date of
the Type A medicated article within the immediate container.
Alternatively, this section must refer to the location on the Type A
medicated article label or immediate container where the lot or control
number and expiration date are printed.
(19) ``Revision Date''. This section of the Type A medicated
article label must include the date of the most recent revision of the
Type A medicated article label, listing the month followed by the year.
(b) Representative Type B medicated feed labeling. The following
information, as applicable, must appear in the order listed on the
representative Type B medicated feed labeling. Section headings,
subsection headings, and other text presented in quotations in this
paragraph must appear verbatim on the representative Type B medicated
feed labeling. Sections and subsections are not numbered on the
representative Type B medicated feed labeling.
(1) Description of the Type B medicated feed. This section of the
representative Type B medicated feed labeling serves as a placeholder
for the
[[Page 18332]]
proprietary name to be added by the feed manufacturer to the label of
the final Type B medicated feed manufactured in accordance with the
approved representative Type B labeling. The description of the Type B
medicated feed must:
(i) Distinguish the Type B medicated feed from any other Type B
medicated feeds approved or conditionally approved within the same
application; and
(ii) Not include the proprietary name of a Type A medicated
article.
(2) Established name of the Type B medicated feed. The established
name of the Type B medicated feed must include in the following order:
(i) The active moiety or active ingredient of each new animal drug,
as determined by FDA; and
(ii) One of the following statements, as applicable: ``Type B
medicated feed'' or ``Type B liquid medicated feed''.
(3) VFD cautionary statement. The requirements of paragraph (a)(2)
of this section apply.
(4) Undiluted statement. This section of the representative Type B
medicated feed labeling must include the statement: ``Do Not Feed
Undiluted.''
(5) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(6) ``Indications for Use''. The requirements of Sec.
201.407(a)(3) apply. Include only the approved or conditionally
approved indications for use for the specific Type B medicated feed to
which the representative Type B medicated feed labeling applies.
(7) Extralabel use statement. The requirements of paragraph (a)(6)
of this section apply.
(8) ``Active Ingredient'' or ``Active Ingredients''. This section
of the representative Type B medicated feed labeling must include the
following information for the specific Type B medicated feed to which
the representative Type B medicated feed labeling applies. If the Type
B medicated feed contains one active ingredient, this section of the
representative Type B medicated feed labeling must be entitled ``Active
Ingredient.'' If the Type B medicated feed contains more than one
active ingredient, this section of the representative Type B medicated
feed labeling must be entitled ``Active Ingredients.''
(i) The established name of each active ingredient; and
(ii) The concentration or range of concentrations of each active
ingredient as approved by FDA. If included as a range, the active
ingredient concentrations must reference a footnote at the bottom of
this page of the representative Type B labeling indicating that each
final printed Type B medicated feed label must only include a single
concentration of each active ingredient.
(9) ``Guaranteed Analysis''. This section of the representative
Type B medicated feed labeling must provide for the nutritional content
guarantees of the Type B medicated feed appropriate for the target
animal(s) in addition to any other required specifications.
(10) ``Ingredients''. This section of the representative Type B
medicated feed labeling must include the following:
(i) A statement that feed ingredients must be listed on each final
printed Type B medicated feed label by their common or usual names in
descending order of predominance by weight, in accordance with Sec.
501.4(a) of this chapter, including their collective names where
permitted, in accordance with Sec. 501.4(b)(13) of this chapter; and
(ii) A statement that spices, flavorings, colorings, and chemical
preservatives, if used, must be declared on each final printed Type B
medicated feed label, in accordance with Sec. 501.22 of this chapter.
(11) ``Mixing Directions''. This section of the representative Type
B medicated feed labeling must provide the approved mixing directions
for the manufacture of a Type C medicated feed(s) or another Type B
medicated feed(s), as applicable, from the Type B medicated feed for
which the representative Type B medicated feed labeling applies.
(12) ``Warnings''. The requirements of paragraph (a)(10) of this
section apply. Include only the warnings for the specific Type B
medicated feed to which the representative Type B medicated feed
labeling applies.
(13) ``Additional Recommendations''. The requirements of Sec.
201.407(a)(8) apply. Include only the precautions for the specific Type
B medicated feed to which the representative Type B medicated feed
labeling applies.
(14) ``Other Effects You May Notice''. The requirements of Sec.
201.407(a)(9) apply. Include only statements of other effects for the
specific Type B medicated feed to which the representative Type B
medicated feed labeling applies.
(15) Name and place of business. This section of the representative
Type B medicated feed labeling must provide for the name and place of
business of the manufacturer, packer, or distributor of the final Type
B medicated feed, in accordance with Sec. 501.5 of this chapter.
(16) ``Net Weight''. This section of the representative Type B
medicated feed labeling must provide for the statement on the final
printed Type B medicated feed label of the net weight of the Type B
medicated feed in the immediate container.
(17) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(18) ``Questions/Comments?''. The following statements must be
included in this section of the representative Type B medicated feed
labeling: ``Contact [name of business] at [business telephone number]
or [business web address]. For additional information about reporting
problems with medicated feeds, contact FDA at [insert current FDA
telephone number for voluntary reporting of adverse drug experiences]
or [insert current FDA web address for voluntary reporting of adverse
drug experiences].'' The information in the bracketed areas of the
first statement are placeholders for the business of the manufacturer,
packer, or distributor of the final Type B medicated feed to insert
their name and contact information. The information in the bracketed
areas of the second statement must be inserted by the sponsor of the
new animal drug application.
(19) ``Lot, Batch, or Control Number''. This section of the
representative Type B medicated feed labeling must provide for an
identifying lot, batch, or control number on the final printed Type B
medicated feed label.
(20) ``Expiration Date''. If an expiration date is required, in
accordance with Sec. 514.1(b)(5)(x) of this chapter, then this section
of the representative Type B medicated feed labeling must provide for
the expiration date to be printed on the final printed Type B medicated
feed label. The approved expiration period must also be included in
this section of the representative Type B medicated feed labeling.
(21) ``Revision Date''. This section of the representative Type B
medicated feed labeling must include the date of the most recent
revision of the representative Type B medicated feed labeling, listing
the month followed by the year.
(c) Representative Type C medicated feed labeling. The following
information, as applicable, must appear in the order listed on the
representative Type C medicated feed labeling. Section headings,
subsection headings, and other text presented in quotations in this
paragraph must appear verbatim on the representative Type C medicated
feed labeling. Sections and subsections are not numbered on the
representative Type C medicated feed labeling.
(1) Description of the Type C medicated feed. This section of the
[[Page 18333]]
representative Type C medicated feed labeling serves as a placeholder
for the proprietary name to be added by the feed manufacturer to the
label of the final Type C medicated feed manufactured in accordance
with the approved representative Type C medicated feed labeling. The
description of the Type C medicated feeds must:
(i) Distinguish the Type C medicated feed from any other Type C
medicated feeds approved or conditionally approved within the same
application; and
(ii) Not include the proprietary name of a Type A medicated
article.
(2) Established name of the Type C medicated feed. The established
name of the Type C medicated feed must include in the following order:
(i) The active moiety or active ingredient of each new animal drug,
as determined by FDA; and
(ii) One of the following statements, as applicable: ``Type C
medicated feed,'' ``Type C liquid medicated feed,'' ``Type C top-dress
medicated feed,'' ``Type C free-choice medicated feed,'' or ``Type C
liquid free-choice medicated feed''.
(3) VFD cautionary statement. The requirements of paragraph (a)(2)
of this section apply.
(4) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(5) ``Indications for Use''. The requirements of Sec.
201.407(a)(3) apply. Include only the approved or conditionally
approved indications for use for the specific Type C medicated feed to
which the representative Type C medicated feed labeling applies.
(6) Extralabel use statement. The requirements of paragraph (a)(6)
of this section apply.
(7) ``Active Ingredient'' or ``Active Ingredients''. This section
of the representative Type C medicated feed labeling must include the
following information for the specific Type C medicated feed to which
the representative Type C medicated feed labeling applies. If the Type
C medicated feed contains one active ingredient, this section of the
representative Type C medicated feed labeling must be entitled ``Active
Ingredient.'' If the Type C medicated feed contains more than one
active ingredient, this section of the representative Type C medicated
feed labeling must be entitled ``Active Ingredients.''
(i) The established name of each active ingredient; and
(ii) The concentration or range of concentrations of each active
ingredient as approved by FDA. If included as a range, the active
ingredient concentrations must reference a footnote at the bottom of
this page of the representative Type C medicated feed labeling
indicating that each final printed Type C medicated feed label must
only include a single concentration of each active ingredient.
(8) ``Guaranteed Analysis''. The requirements of paragraph (b)(9)
of this section apply.
(9) ``Ingredients''. This section of the representative Type C
medicated feed labeling must include the following:
(i) For Type C medicated feeds that are not Type C free-choice
medicated feeds:
(A) A statement that feed ingredients must be listed on each final
printed Type C medicated feed label by their common or usual names in
descending order of predominance by weight, in accordance with Sec.
501.4(a) of this chapter, including their collective names where
permitted, in accordance with Sec. 501.4(b)(13) of this chapter; and
(B) A statement that spices, flavorings, colorings, and chemical
preservatives, if used, must be declared on each final printed Type C
medicated feed label, in accordance with Sec. 501.22 of this chapter.
(ii) For Type C free-choice medicated feeds, a list of the feed
ingredients and their inclusion rates, including the drug
concentrations exactly as they appear in the approved non-proprietary
formula published for the specific new animal drug in part 558 of this
chapter.
(10) ``Feeding Directions''. The requirements of paragraph
(a)(9)(iii) of this section apply. This section of the representative
Type C medicated feed labeling must include the approved feeding
directions for the specific Type C medicated feed for which the
representative Type C medicated feed labeling applies.
(11) ``Warnings''. The requirements of paragraph (a)(10) of this
section apply. Include only the warnings for the specific Type C
medicated feed to which the representative Type C medicated feed
labeling applies.
(12) ``Additional Recommendations''. The requirements of Sec.
201.407(a)(8) apply. Include only the precautions for the specific Type
C medicated feed to which the representative Type C medicated feed
labeling applies.
(13) ``Other Effects You May Notice''. The requirements of Sec.
201.407(a)(9) apply. Include only statements of other effects for the
specific Type C medicated feed to which the representative Type C
medicated feed labeling applies.
(14) Name and place of business. This section of the representative
Type C medicated feed labeling must provide for the name and place of
business of the manufacturer, packer, or distributor of the final Type
C medicated feed, in accordance with Sec. 501.5 of this chapter.
(15) ``Net Weight''. This section of the representative Type C
medicated feed labeling must provide for the statement of net weight on
the final printed Type C medicated feed label of the Type C medicated
feed in the immediate container.
(16) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(17) ``Questions/Comments?''. The following statements must be
included in this section of the representative Type C medicated feed
labeling: ``Contact [name of business] at [business telephone number]
or [business web address]. For additional information about reporting
side effects or other problems with medicated feeds, contact FDA at
[insert current FDA telephone number for voluntary reporting of adverse
drug experiences] or [insert current FDA web address for voluntary
reporting of adverse drug experiences].'' The information in the
bracketed areas of the first statement are placeholders for the
business of the manufacturer, packer, or distributor of the final Type
C medicated feed to insert their name and contact information. The
information in the bracketed areas of the second statement must be
inserted by the sponsor of the new animal drug application.
(18) ``Lot, Batch, or Control Number''. This section of the
representative Type C medicated feed labeling must provide for an
identifying lot, batch, or control number on the final printed Type C
medicated feed label.
(19) ``Expiration Date''. If an expiration date is required, in
accordance with Sec. 514.1(b)(5)(x) of this chapter, then this section
of the representative Type C medicated feed labeling must provide for
the expiration date to be printed on the final printed Type C medicated
feed label. The approved expiration period must also be included in
this section of the representative Type C medicated feed labeling.
(20) ``Revision Date''. This section of representative Type C
medicated feed labeling must include the date of the most recent
revision of the representative Type C medicated feed labeling, listing
the month followed by the year.
(d) Proprietary Type B medicated feed label. The following
information, as applicable, must appear in the order listed on the
proprietary Type B medicated feed label. Section headings, subsection
headings, and other text
[[Page 18334]]
presented in quotations in this paragraph must appear verbatim on the
proprietary Type B medicated feed label. Sections and subsections are
not numbered on the proprietary Type B medicated feed label.
(1) Proprietary Type B medicated feed identification. This section
of the proprietary Type B medicated feed label must include in order:
(i) Proprietary name of the Type B medicated feed; and
(ii) Established name of the Type B medicated feed. The established
name of the Type B medicated feed must include in the following order:
(A) The active moiety or active ingredient of each new animal drug,
as determined by FDA; and
(B) One of the following statements, as applicable: ``Type B
medicated feed'' or ``Type B liquid medicated feed''.
(2) VFD cautionary statement. The requirements of paragraph (a)(2)
of this section apply.
(3) Undiluted statement. This section of the proprietary Type B
medicated feed label must include the statement: ``Do Not Feed
Undiluted''.
(4) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(5) ``Indications for Use''. The requirements of Sec.
201.407(a)(3) apply.
(6) Extralabel use statement. The requirements of paragraph (a)(6)
of this section apply.
(7) ``Active Ingredient'' or ``Active Ingredients''. This section
of the proprietary Type B medicated feed label must include the
established name and concentration of each active ingredient in the
proprietary Type B medicated feed. If the proprietary Type B medicated
feed contains one active ingredient, this section of the proprietary
Type B medicated feed label must be entitled ``Active Ingredient.'' If
the proprietary Type B medicated feed contains more than one active
ingredient, this section of the proprietary Type B medicated feed label
must be entitled ``Active Ingredients.''
(8) ``Guaranteed Analysis''. This section of the proprietary Type B
medicated feed label must provide the nutritional content guarantees of
the proprietary Type B medicated feed appropriate for the target
animal(s) in addition to any other required specifications.
(9) ``Ingredients''. This section of the proprietary Type B
medicated feed label must include:
(i) A listing of the feed ingredients in the proprietary Type B
medicated feed by their common or usual names in descending order of
predominance by weight, in accordance with Sec. 501.4(a) of this
chapter, including their collective names where permitted, in
accordance with Sec. 501.4(b)(13) of this chapter; and
(ii) A declaration of spices, flavorings, colorings, and chemical
preservatives, if used, in accordance with Sec. 501.22 of this
chapter.
(10) ``Mixing Directions''. This section of the proprietary Type B
medicated feed label must provide the approved mixing directions for
the manufacture of a Type C medicated feed(s) or another Type B
medicated feed(s), as applicable, from the proprietary Type B medicated
feed.
(11) ``Warnings''. The requirements of paragraph (a)(10) of this
section apply.
(12) ``Additional Recommendations''. The requirements of Sec.
201.407(a)(8) apply.
(13) ``Other Effects You May Notice''. The requirements of Sec.
201.407(a)(9) apply.
(14) ``Net Weight''. This section of the proprietary Type B
medicated feed label must list the net weight of the Type B medicated
feed in the immediate container.
(15) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(16) ``Questions/Comments?''. The following statements must be
included in this section of the proprietary Type B medicated feed
label: ``Contact [insert name of business] at [insert business
telephone number] or [insert business web address]. For additional
information about reporting problems with medicated feeds, contact FDA
at [insert current FDA telephone number for voluntary reporting of
adverse drug experiences] or [insert current FDA web address for
voluntary reporting of adverse drug experiences].'' Use as the name of
the business the manufacturer, packer, or distributor identified in the
``Name and place of business'' section of the proprietary Type B
medicated feed label according to paragraph (d)(18) of this section. If
more than one business is identified in the ``Name and place of
business'' section of the proprietary Type B medicated feed label,
select the most appropriate to identify as the ``business'' in the
``Questions/Comments?'' section of the proprietary Type B medicated
feed label to provide additional information about the Type B medicated
feed and to contact regarding problems with this medicated feed.
(17) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(18) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(19) ``Lot, Batch, or Control Number''. This section of the
proprietary Type B medicated feed label must include the identifying
lot, batch, or control number of the Type B medicated feed.
Alternatively, this section must refer to the location on the
proprietary Type B medicated feed label or immediate container where
the lot, batch, or control number is printed.
(20) ``Expiration Date''. If an expiration date is required, in
accordance with Sec. 514.1(b)(5)(x) of this chapter, this section must
be included on the proprietary Type B medicated feed label and must
provide the expiration date of the proprietary Type B medicated feed.
Alternatively, this section must refer to the location on the
proprietary Type B medicated feed label or immediate container where
the expiration date is printed.
(21) ``Revision Date''. This section of the proprietary Type B
medicated feed label must include the date of the most recent revision
of the proprietary Type B medicated feed label, listing the month
followed by the year.
(e) Proprietary Type C medicated feed label. The following
information, as applicable, must appear in the order listed on the
proprietary Type C medicated feed label. Section headings, subsection
headings, and other text presented in quotations in this paragraph must
appear verbatim on the proprietary Type C medicated feed label.
Sections and subsections are not numbered on the proprietary Type C
medicated feed label.
(1) Proprietary Type C medicated feed identification. This section
of the proprietary Type C medicated feed label must include in order:
(i) Proprietary name of the Type C medicated feed; and
(ii) Established name of the Type C medicated feed. The established
name of the Type C medicated feed must include in the following order:
(A) The active moiety or active ingredient of each new animal drug,
as determined by FDA; and
(B) One of the following statements, as applicable: ``Type C
medicated feed,'' ``Type C liquid medicated feed,'' ``Type C top-dress
medicated feed,'' ``Type C free-choice medicated feed,'' or ``Type C
liquid free-choice medicated feed.''
(2) VFD cautionary statement. The requirements of paragraph (a)(2)
of this section apply.
(3) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(4) ``Indications for Use''. The requirements of Sec.
201.407(a)(3) apply.
[[Page 18335]]
(5) Extralabel use statement. The requirements of paragraph (a)(6)
of this section apply.
(6) ``Active Ingredient'' or ``Active Ingredients''. This section
of the proprietary Type C medicated feed label must include the
established name and concentration of each active ingredient in the
proprietary Type C medicated feed. If the proprietary Type C medicated
feed contains one active ingredient, this section of the proprietary
Type C medicated feed label must be entitled ``Active Ingredient.'' If
the proprietary Type C medicated feed contains more than one active
ingredient, this section of the proprietary Type C medicated feed label
must be entitled ``Active Ingredients.''
(7) ``Guaranteed Analysis''. The requirements of paragraph (d)(8)
of this section apply.
(8) ``Ingredients''. The requirements of paragraph (d)(9) of this
section apply.
(9) ``Feeding Directions''. This section of the proprietary Type C
medicated feed label must include the approved feeding directions for
the proprietary Type C medicated feed.
(10) ``Warnings''. The requirements of paragraph (a)(10) of this
section apply.
(11) ``Additional Recommendations''. The requirements of Sec.
201.407(a)(8) apply.
(12) ``Other Effects You May Notice''. The requirements of Sec.
201.407(a)(9) apply.
(13) ``Net Weight''. This section of the proprietary Type C
medicated feed label must list the net weight of the Type C medicated
feed in the immediate container.
(14) ``Storage, Handling, and Disposal''. The requirements of Sec.
201.405(a)(20) apply.
(15) ``Questions/Comments?''. The following statements must be
included in this section of the proprietary Type C medicated feed
label: ``Contact [insert name of business] at [insert business
telephone number] or [insert business web address]. For additional
information about reporting side effects or other problems with
medicated feeds, contact FDA at [insert current FDA telephone number
for voluntary reporting of adverse drug experiences] or [insert current
FDA web address for voluntary reporting of adverse drug experiences].''
Use as the name of the business the manufacturer, packer, or
distributor identified in the ``Name and place of business'' section of
the proprietary Type C medicated feed label according to paragraph
(e)(17) of this section. If more than one business is identified in the
``Name and place of business'' section of the proprietary Type C
medicated feed label, select the most appropriate to identify as the
``business'' in the ``Questions/Comments?'' section of the proprietary
Type C medicated feed label to provide additional information about the
Type C medicated feed and to contact regarding suspected adverse drug
experiences.
(16) NADA/ANADA approval statement. For approved new animal drugs
or approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(17) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(18) ``Lot, Batch, or Control Number''. This section of the
proprietary Type C medicated feed label must include the identifying
lot, batch, or control number of the Type C medicated feed.
Alternatively, this section must refer to the location on the
proprietary Type C medicated feed label or immediate container where
the lot, batch, or control number is printed.
(19) ``Expiration Date''. If an expiration date is required, in
accordance with Sec. 514.1(b)(5)(x) of this chapter, this section must
be included on the proprietary Type C medicated feed label and must
provide the expiration date of the proprietary Type C medicated feed
label. Alternatively, this section must refer to the location on the
proprietary Type C medicated feed label or immediate container where
the expiration date is printed.
(20) ``Revision Date''. This section of the proprietary Type C
medicated feed label must include the date of the most recent revision
of the proprietary Type C medicated feed label, listing the month
followed by the year.
(f) Other approved labeling for Type A medicated articles. If other
approved labeling associated with approved or conditionally approved
Type A medicated articles is provided (other approved labeling for Type
A medicated articles), such as shipping labeling, the following
information, as applicable, must appear in the order listed on the
other approved labeling for Type A medicated articles. Section headings
and other text presented in quotations in this paragraph must appear
verbatim on the other approved labeling for Type A medicated articles.
Sections are not numbered on other approved labeling for Type A
medicated articles.
(1) Type A medicated article identification. This section of the
other approved labeling for Type A medicated articles must include in
order:
(i) Proprietary name of the Type A medicated article; and
(ii) Established name of the Type A medicated article.
(2) VFD cautionary statement. The requirements of paragraph (a)(2)
of this section apply.
(3) ``Active Ingredient'' or ``Active Ingredients''. This section
of the other approved labeling for Type A medicated articles must
provide the established name and concentration of each active
ingredient in the Type A medicated article. If the Type A medicated
article contains one active ingredient, this section of the other
approved labeling for Type A medicated articles must be entitled
``Active Ingredient.'' If the Type A medicated article contains more
than one active ingredient, this section of the other approved labeling
for Type A medicated articles must be entitled ``Active Ingredients.''
(4) Conditional approval statement. The requirements of Sec.
201.405(a)(3) apply.
(5) ``Net Contents''. This section of the other approved labeling
for Type A medicated articles must identify the contents of the
container to which the other approved labeling for Type A medicated
articles applies.
(6) ``Storage and Handling''. This section of the other approved
labeling for Type A medicated articles must include storage information
for the Type A medicated article. If required by FDA to facilitate the
drug's safe and effective use, also include handling information.
(7) NADA/ANADA approval statement. For approved new animal drugs or
approved generic new animal drugs, the requirements of Sec.
201.405(a)(21) apply.
(8) Name and place of business. The requirements of Sec.
201.405(a)(22) apply.
(9) ``Lot Number and Expiration Date''. This section of the other
approved labeling for Type A medicated articles must include the
identifying lot or control number(s) and the expiration date(s) of the
Type A medicated article within the container.
(10) ``Revision Date''. This section of the other approved labeling
for Type A medicated articles must include the date of the most recent
revision of the other approved labeling for Type A medicated articles,
listing the month followed by the year.
Sec. 201.411 Exemptions from labeling requirements for approved or
conditionally approved new animal drugs.
(a) In response to a request from the sponsor that includes the
information in paragraph (b) of this section, FDA may exempt, based on
the circumstances presented, one or more specific requirements set
forth in this subpart. A separate request must be submitted for each
approved or conditionally approved new animal drug for which an
[[Page 18336]]
exemption is sought. Sponsors must submit such requests to the
application or the investigational new animal drug file (INAD) for the
new animal drug. Requests will be granted or denied by the Director of
FDA's Center for Veterinary Medicine or the Director's designee.
(b) Exemption requests must:
(1) Describe why the particular requirement for which the exemption
is requested is not appropriate for the new animal drug;
(2) Describe why granting the exemption would not adversely impact
the safety or effectiveness of the use of the new animal drug; and
(3) Include copies of all draft labeling proposed to be used for
the new animal drug.
Sec. 201.413 Labeling requirements for certain approved or
conditionally approved new animal drugs.
In addition to labeling requirements elsewhere in this subpart, the
labeling requirements in this section apply to the following approved
or conditionally approved new animal drugs:
(a) Approved or conditionally approved corticosteroid-containing
new animal drugs for oral, injectable, and/or ophthalmic use. Approved
or conditionally approved corticosteroid-containing new animal drugs
for oral, injectable, and/or ophthalmic use are subject to the labeling
requirements for Rx new animal drugs in this subpart. In view of
adverse reproductive effects associated with use of certain
corticosteroid drugs in animals, approved or conditionally approved
corticosteroid new animal drugs intended for oral and/or injectable use
must also include the following statements in the ``Animal Safety
Warnings and Precautions'' subsection of labeling: ``Clinical and
experimental data have demonstrated that corticosteroids administered
orally or by injection to animals may induce the first stage of
parturition if used during the last trimester of pregnancy and may
precipitate premature parturition followed by dystocia, fetal death,
retained placenta, and metritis. Additionally, corticosteroids
administered during pregnancy can be teratogenic.'' These statements
must also be included in the ``Animal Safety Warnings and Precautions''
subsection of labeling for approved or conditionally approved
corticosteroid new animal drugs intended for ophthalmic use, if
required by FDA to facilitate the drug's safe and effective use.
(b) Anthelmintic new animal drugs--(1) OTC anthelmintic new animal
drugs. To ensure that OTC anthelmintic new animal drugs provide
adequate directions for their effective use, all approved or
conditionally approved OTC anthelmintic new animal drugs, including OTC
anthelmintic new animal drugs for use in animal feeds, must include the
following statement in the ``Additional Recommendations'' section of
labeling: ``Consult your veterinarian for assistance in the diagnosis,
treatment, and control of parasitism.''
(2) Anthelmintic new animal drugs for use in sheep, goats, cattle,
horses, swine, and/or poultry. All approved or conditionally approved
anthelmintic new animal drugs for use in sheep, goats, cattle, horses,
swine, and/or poultry must include statements on their labeling
providing information to end users to minimize antiparasitic resistance
development, including information on appropriate dosing, anthelmintic
drug selection, effectiveness monitoring, the integration of
anthelmintic drug use with other parasite management practices, and
other information as needed. The statements must be included in the
``Other Warnings'' subsection of labeling, and if applicable,
additional statements may be required in the ``Dosage and
Administration'' section of labeling for Rx anthelmintic new animal
drugs, the ``Directions'' section of labeling for OTC anthelmintic new
animal drugs, or the ``Feeding Directions'' section or subsection of
labeling for anthelmintic new animal drugs for use in animal feeds.
(c) New animal drugs for use in horses. All new animal drugs
approved or conditionally approved for use in horses must include in
the ``Other Warnings'' subsection of labeling a statement advising
against the use of the drug in horses intended for human consumption.
PART 500--GENERAL
0
6. The authority citation for part 500 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 353,
360b, 371, 379e.
Sec. Sec. 500.25 and 500.55 [Removed]
0
7. Remove Sec. Sec. 500.25 and 500.55.
PART 501--ANIMAL FOOD LABELING
0
8. The authority citation for part 501 continues to read as follows:
Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342,
343, 348, 371.
0
9. Add Sec. 501.19 to subpart A to read as follows:
Sec. 501.19 Animal food; labeling of animal food containing new
animal drugs.
The requirements for the labeling of animal food containing an
approved or conditionally approved new animal drug are found in Sec.
201.409 of this chapter. Requirements of this part apply only as
specified in Sec. 201.409.
PART 510--NEW ANIMAL DRUGS
0
10. The authority citation for part 510 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.
Sec. Sec. 510.105, 510.106, and 510.410 [Removed]
0
11. Remove Sec. Sec. 510.105, 510.106, and 510.410.
PART 514--NEW ANIMAL DRUG APPLICATIONS
0
12. The authority citation for part 514 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 354, 356a, 360b,
360ccc, 371, 379e, 381.
0
13. In Sec. 514.1, revise paragraph (b)(3) to read as follows:
Sec. 514.1 Applications.
* * * * *
(b) * * *
(3) Labeling. Three copies of each piece of all labeling to be used
for the article (total of 9).
(i) All labeling should be identified to show its position on, or
the manner in which it is to accompany the market package.
(ii) The content and format of all proposed labeling must comply
with subpart H of part 201 of this chapter.
(iii) Labeling for nonprescription new animal drugs should include
adequate directions for use by the layperson under all conditions of
use for which the new animal drug is intended, recommended, or
suggested in any of the labeling or advertising sponsored by the
applicant.
(iv) Labeling for prescription new animal drugs should bear
adequate information for use under which veterinarians can use the new
animal drug safely and for the purposes for which it is intended,
including those purposes for which it is to be advertised or
represented, in accord with Sec. 201.105 of this chapter.
(v) All labeling for prescription or nonprescription new animal
drugs must be submitted with any necessary use restrictions prominently
and conspicuously displayed.
(vi) Labeling for new animal drugs intended for use in the
manufacture of medicated feeds must include:
[[Page 18337]]
(A) Specimens of labeling to be used for such new animal drug with
adequate directions for the manufacture and use of finished feeds for
all conditions for which the new animal drug is intended, recommended,
or suggested in any of the labeling, including advertising, sponsored
by the applicant. Ingredient labeling may utilize collective names as
provided in Sec. 501.110 of this chapter.
(B) Representative labeling proposed to be used for Type B and Type
C medicated feeds containing the new animal drug.
(vii) Draft labeling may be submitted for preliminary consideration
of an application. Final printed labeling will ordinarily be required
prior to approval of an application. Proposed advertising for
prescription new animal drugs may be submitted for comment or approval.
* * * * *
PART 516--NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES
0
14. The authority citation for part 516 continues to read as follows:
Authority: 21 U.S.C. 360ccc-1, 360ccc-2, 371.
0
15. In Sec. 516.155, redesignate paragraph (c) as paragraph (d) and
add a new paragraph (c) to read as follows:
Sec. 516.155 Labeling of indexed drugs.
* * * * *
(c) To ensure that OTC anthelmintic new animal drugs provide
adequate directions for their effective use, the labeling of all OTC
indexed anthelmintic drugs, including those used in animal feeds, must
include the following statement: ``Consult your veterinarian for
assistance in the diagnosis, treatment, and control of parasitism.''
The labeling revisions required for compliance with this section may be
placed into effect without prior granting of a request for a
modification, as provided for in Sec. 516.161(b)(1).
* * * * *
Dated: March 1, 2024.
Robert M. Califf,
Commissioner of Food and Drugs.
[FR Doc. 2024-04840 Filed 3-8-24; 8:45 am]
BILLING CODE 4164-01-P
