New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food, 74962-74966 [2016-26043]
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Federal Register / Vol. 81, No. 209 / Friday, October 28, 2016 / Proposed Rules
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AV = Total adjusted volume, expressed in ft3, as calculated according to appendix A of subpart B of this part.
[FR Doc. 2016–24758 Filed 10–27–16; 8:45 am]
BILLING CODE 6450–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 514 and 556
[Docket No. FDA–2012–N–1067]
RIN 0910–AG17
New Animal Drugs; Updating
Tolerances for Residues of New
Animal Drugs in Food
AGENCY:
Food and Drug Administration,
HHS.
Proposed rule; supplemental
notice of proposed rulemaking.
ACTION:
The Food and Drug
Administration (FDA or we) is
proposing to amend our 2012 document
entitled ‘‘New Animal Drugs; Updating
Tolerances for Residues of New Animal
Drugs in Food.’’ The document
proposed to revise the animal drug
regulations regarding tolerances for
residues of approved and conditionally
approved new animal drugs in food by
standardizing, simplifying, and
clarifying the determination standards
and codification style. We also proposed
to add definitions for key terms. We are
taking this action to more clearly
explain our current thinking about
certain provisions of the 2012 document
based on comments from stakeholders,
and to more accurately reflect the
rationale FDA relied on in the past to
approve certain new animal drugs
without a tolerance. We are reopening
the comment period only with respect
to the specific issues identified in this
supplemental proposed rule.
DATES: Submit either electronic or
written comments on this proposed rule
by December 27, 2016.
ADDRESSES: You may submit comments
as follows:
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SUMMARY:
Electronic Submissions
Submit electronic comments in the
following way:
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• 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 Submission
Submit written/paper submissions as
follows:
• Mail/Hand delivery/Courier (for
written/paper submissions): Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Division of Dockets
Management, 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–
2012–N–1067 for this proposed
rulemaking. Received comments will be
placed in the docket and, except for
those submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday.
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• 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 Division of Dockets
Management. 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.fda.gov/
regulatoryinformation/dockets/
default.htm.
Docket: For access to the docket to
read background documents 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 Division of Dockets
Management, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Dong Yan, Center for Veterinary
Medicine (HFV–151), Food and Drug
Administration, 7500 Standish Pl.,
Rockville, MD 20855, 240–402–0825,
dong.yan@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
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Table of Contents
Executive Summary
Purpose and Coverage of the Supplemental
Notice of Proposed Rulemaking
Summary of the Major Provisions of the
Supplemental Notice of Proposed
Rulemaking
I. Background
A. Introduction
B. Comments to the 2012 Proposed Rule for
Updating Tolerances for Residues of
New Animal Drugs in Food
II. Proposed Revisions to Subpart A—General
Provisions
A. Analytical Method
B. Proposed Revisions to Definitions
(Proposed § 556.3)
C. Proposed Revisions to General
Considerations (Proposed § 556.5)
III. Proposed Conforming Change to 21 CFR
Part 514
IV. Legal Authority
V. Economic Analysis of Impacts
VI. Paperwork Reduction Act of 1995
VII. Analysis of Environmental Impact
VIII. Federalism
IX. References
Executive Summary
Purpose and Coverage of the
Supplemental Notice of Proposed
Rulemaking
We previously proposed to revise the
animal drug regulations regarding
tolerances for residues of approved and
conditionally approved new animal
drugs in food. In addition to proposing
to standardize, simplify, and clarify the
standards of determination and
codification style for tolerances, we
proposed a new definition section. In
this document, we are proposing to
revise or remove some of the previously
proposed definitions, taking into
account comments we received that
have led us to clarify our current
thinking, and to more accurately reflect
the rationale FDA relied on in the past
to approve certain new animal drugs
without a tolerance.
Summary of the Major Provisions of the
Supplemental Notice of Proposed
Rulemaking
The previously proposed rule (2012
proposed rule) did not adequately
explain our current view that methods
other than the ‘‘regulatory method’’
derived from the method submitted by
a sponsor as part of the new animal drug
application can be used to determine
the quantity of residue in edible tissues
for surveillance and enforcement
purposes. Therefore, we are removing
the proposed definition for ‘‘regulatory
method’’ and are reserving the term for
use with carcinogenic compounds. We
are also removing the use of this term
74963
from proposed § 556.5(d) (21 CFR
556.5(d)). We are proposing to revise
portions of the 2012 proposed rule to
better align the proposed rule with our
current thinking and practice that an
analytical method other than the
practicable method(s) submitted by the
sponsor as part of the new animal drug
application can be used for surveillance
and enforcement purposes for noncarcinogenic compounds, as long as the
performance criteria of that method are
comparable to those of the practicable
method. However, as described in
section II.C, we are not proposing
similar changes to the regulations
concerning carcinogenic compounds
because our current interpretation of the
relevant provisions in the Federal Food,
Drug, and Cosmetic Act (the FD&C Act)
is that, unlike for non-carcinogenic
compounds, the regulatory method
prescribed in the approval of the new
animal drug must be used for
surveillance and enforcement purposes
for carcinogenic compounds.
We are also revising the proposed
definitions for ‘‘marker residue’’,
‘‘tolerance’’, ‘‘not required’’, and ‘‘zero’’.
We are removing the definition for
‘‘acceptable single-dose intake’’ and
adding a definition for ‘‘acute reference
dose’’.
TABLE OF ABBREVIATIONS AND ACRONYMS
Abbreviation/acronym
What it means
ARfD ............................................
ASDI ............................................
CFR .............................................
CVM .............................................
FDA .............................................
FD&C Act ....................................
JECFA .........................................
Acute reference dose.
Acceptable single-dose intake.
Code of Federal Regulations.
Center for Veterinary Medicine.
U.S. Food and Drug Administration.
Federal Food, Drug, and Cosmetic Act.
World Health Organization/Food and Agriculture Organization of the United Nations Joint Expert Committee
on Food Additives.
International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products.
VICH ............................................
I. Background
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A. Introduction
In the Federal Register of December 5,
2012 (77 FR 72254), we issued a
document to revise part 556 (21 CFR
part 556) by standardizing and
simplifying the codification style,
revising the general considerations
section, adding a scope section, and
adding a definition section to define key
terms used in the part. The definition
section was proposed to include the
terms used by FDA in the determination
of tolerances. Some of the terms had
been used previously in part 556, but
never defined, and some terminology
that had been used was outdated or
resulted in confusion to users of the
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part. We proposed a general
considerations section (proposed
§ 556.5) to provide additional
information and clarification for the
tolerances listed in proposed subpart B.
We are issuing this supplemental notice
of proposed rulemaking to revise the
proposed changes to part 556 to align
with our current thinking.
B. Comments to the 2012 Proposed Rule
for Updating Tolerances for Residues of
New Animal Drugs in Food
We received several stakeholder
comments to the proposed rule
including a comment that requests
clarification on the proposed definition
for ‘‘regulatory method’’ and on the use
of the term in proposed § 556.5(d),
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which stated that FDA requires that a
drug sponsor develop a regulatory
method to measure drug residues in
edible tissues of approved target
species. This comment notes that a
regulatory method has historically been
used to refer to the ‘‘required
determinative and confirmatory
procedures for regulatory surveillance of
residue concentrations in meat products
entering the food supply for comparison
to the tolerance post-commercialization
of the product.’’ The comment also
states the context of the proposal
appears to be the method(s) used to
collect data to support the setting of the
tolerances preapproval. The comment
also asks if the proposal implies that
tolerances may be established using
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analytical procedures other than the
determinative procedure. In addition,
the comment states it should be clarified
if regulatory method is referring to
method(s) used preapproval for setting
the tolerance versus a finite method(s)
used for determining postcommercialization residue to compare
to the tolerance.
We realize that the term ‘‘regulatory
method’’ proposed in § 556.3 and used
in proposed § 556.5(d) has caused some
confusion. As a result of the comments,
we are taking this opportunity to better
explain our current thinking about
analytical methods used to determine
residue levels in tissues for new animal
drugs intended for use in foodproducing animals.
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II. Proposed Revisions to Subpart A—
General Provisions
A. Analytical Method
An analytical method other than the
practicable method can be used for
surveillance and enforcement purposes
for non-carcinogenic compounds, as
long as the performance criteria (e.g.,
sensitivity, specificity, accuracy, and
precision) of that method are
comparable to those of the practicable
method submitted by the sponsor as
part of the new animal drug application.
Such an analytical method would need
to have the same capability as the
practicable method to determine the
quantity of the drug residues so that the
tolerance, withdrawal period, or other
use restrictions continue to ensure that
the use of the drug will be safe.
However, as described in section II.C,
for carcinogenic compounds, the
regulatory method prescribed in the
approval of the new animal drug must
be used for surveillance and
enforcement purposes for carcinogenic
compounds (see 21 CFR part 500,
subpart E).
FDA establishes tolerances using the
practicable method submitted by a
sponsor as part of the new animal drug
application as required by section
512(b)(1)(G) of the FD&C Act (21 U.S.C.
360b(b)(1)(G)). The practicable method
has to meet certain performance criteria,
including evaluation of accuracy,
precision, and sensitivity. We use the
practicable method submitted by the
sponsor as part of the new animal drug
application to determine the quantity of
the drug residues that can safely remain
in edible tissues (i.e., the tolerance), the
withdrawal period, and any other use
restrictions necessary to ensure that the
proposed use of the drug will be safe,
and make these use restrictions part of
the conditions of approval. These
conditions of use are designed to ensure
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that the proposed use of the drug will
be safe § 514.1(b)(7) (21 CFR
514.1(b)(7)). In the past, the practicable
method was often used for determining
the quantity of residue in edible tissue
when monitoring the food supply.
However, as technologies have evolved,
many of the older methods have become
obsolete. In addition, there is an
increased reliance on multiresidue
methods in the monitoring of the food
supply (i.e., methods that analyze for a
number of different drug residues at the
same time). As a result, we are clarifying
that an analytical method other than the
practicable method can be used for
surveillance and enforcement purposes
for non-carcinogenic compounds,
provided it meets the same performance
criteria as the practicable method to
determine the quantity of the relevant
drug residues. Therefore, we are
proposing to revise some of the
definitions in proposed § 556.3 of the
2012 proposed rule as well as revise
some of the language under ‘‘General
Considerations’’ in proposed § 556.5, to
more accurately reflect our current
thinking.
B. Proposed Revisions to Definitions
(Proposed § 556.3)
In the 2012 proposed rule, we
included a section of definitions
(proposed § 556.3). We propose to revise
four of the definitions, remove two
definitions, and add a new definition in
proposed § 556.3.
In the definition of ‘‘marker residue’’,
we propose to delete ‘‘selected for assay
by the regulatory method’’ because we
are reserving the term ‘‘regulatory
method’’ for use with carcinogenic
compounds (see part 500, subpart E).
Also, we propose to delete the
explanatory text that follows the first
sentence of the definition because an
explanation of how the tolerance is used
is not needed in this definition. In
addition, we are removing the term
‘‘target tissue’’ in the definition and
replacing it with ‘‘an edible tissue’’.
In the definition of ‘‘not required’’, we
propose to more accurately reflect the
rationale FDA relied on in the past to
approve certain new animal drugs
without a tolerance. Currently, our
general practice is to establish a
tolerance for all new animal drugs we
approve.
In the definition of ‘‘tolerance’’, we
propose to delete the explanatory text
that follows the first sentence of the
definition because an explanation of
how the tolerance is used is not needed
in this definition.
In the definition of ‘‘zero’’, we
propose to delete ‘‘when using a method
of detection prescribed or approved by
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FDA’’ because, as discussed previously,
an analytical method other than the
practicable method can be used for
surveillance and enforcement purposes
for non-carcinogenic compounds. The
additional proposed revisions to this
definition are intended to clarify the
meaning of the term ‘‘zero’’ as used in
part 556 so that ‘‘zero’’ means any
residues detected in the tissue renders
it unsafe.
We propose to remove the definition
of ‘‘acceptable single-dose intake
(ASDI)’’. See discussion for ‘‘acute
reference dose (ARfD)’’ further in this
section for the explanation.
We propose to remove the definition
of ‘‘regulatory method’’ because we are
reserving the term ‘‘regulatory method’’
for use with carcinogenic compounds,
consistent with our current
interpretation of the FD&C Act (see part
500, subpart E).
We propose to add the definition of
‘‘acute reference dose (ARfD)’’ to mean
‘‘an estimate of the amount of residues
expressed on a body weight basis that
can be ingested in a period of 24 hours
or less without adverse effects or harm
to the health of the human consumer.’’
ARfD would be used in place of ASDI
wherever this term is currently used in
the tolerances listed in subpart B of part
556.
In the 2012 proposed rule, we
explained that sometimes the concept of
an ASDI was used to calculate
tolerances. We proposed to define the
ASDI as ‘‘the amount of total residue
that may safely be consumed in a single
meal. The ASDI may be used to derive
the tolerance for residue of a drug at the
injection site where the drug is
administered according to the label.’’
The definition of the ASDI was based on
the U.S. Environmental Protection
Agency definition of ARfD and chosen,
in part, to provide additional clarity for
the veterinary drug health based
guidance value. Since that time, the use
of the term ARfD has been more broadly
applied by scientific and regulatory
authorities, as further discussed in this
section.
The United States is an active member
of the Codex Alimentarius and the
Codex Committee for Residues of
Veterinary Drugs in Food, which rely on
the World Health Organization/Food
and Agriculture Organization of the
United Nations Joint Expert Committee
on Food Additives (JECFA) for scientific
advice. The JECFA uses the guidance
Environmental Health Criteria (EHC)
240, Principles and Methods for the
Risk Assessment of Chemicals in Food
in its evaluations (Ref. 1). This guidance
defines and discusses the term ARfD.
More importantly for FDA, the
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International Cooperation on
Harmonisation of Technical
Requirements for Registration of
Veterinary Medicinal Products (VICH)
has also developed guidelines that
discuss the ARfD. The United States is
a member of VICH and adopts finalized
VICH guidelines for technical
requirements for new animal drug
approvals in the United States. On June
1, 2015 (80 FR 31041), we announced a
draft guidance (Guidance for Industry
#232 (VICH GL54)) entitled ‘‘Studies to
Evaluate the Safety of Residues of
Veterinary Drugs in Human Food:
General Approach to Establish an Acute
Reference Dose (ARfD)’’, in which the
term ‘‘acute reference dose (ARfD)’’ is
used to describe the same concept as the
2012 proposed definition of ASDI (Ref.
2). There are no fundamental differences
between the meaning of ASDI and
ARfD.
We consider it appropriate to propose
using the VICH definition of ARfD to
replace the 2012 proposed definition of
ASDI. The ARfD may be used in the
same manner as the ASDI, which is to
derive the tolerance for residues of a
drug at an injection site where the drug
is administered according to the label,
or to derive the tolerance for residues of
a drug in other edible tissues as a result
of concern for the acute toxicity of the
residues of the veterinary drug.
C. Proposed Revisions to General
Considerations (Proposed § 556.5)
We propose to revise proposed
§ 556.5(d) to align with our current
thinking. In addition, we propose to
remove the term ‘‘regulatory method’’
from this provision because we are
reserving this term for use with
carcinogenic compounds (part 500,
subpart E).
Although the proposed revisions
would clarify that an analytical method
other than the practicable method may
be used for surveillance and
enforcement purposes for residue levels
of non-carcinogenic animal drugs, with
regard to approved carcinogenic
compounds, our current interpretation
of the relevant provisions of the FD&C
Act is that it requires that a regulatory
method be prescribed for such a
compound and used for surveillance
and enforcement purposes. Under the
Delaney Clause, section 512(d)(1)(I) of
the FD&C Act, FDA cannot approve an
application for a new animal drug if it
is found to induce cancer when ingested
by humans or animals. An exception to
this provision, referred to as the DES
(diethylstilbestrol) Proviso, allows for
the approval of a carcinogenic
compound if FDA finds that, under the
approved conditions of use, the drug
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will not adversely affect treated animals
and no residue of the drug will be found
(by methods of examination prescribed
or approved by the Secretary by
regulations) (emphasis added) in any
food for human consumption derived
from the treated animals (see section
512(d)(1)(I)(i) and (ii) of the FD&C Act).
FDA has issued regulations defining the
operational definition of no residue and
regulatory method for purposes of
measuring carcinogenic compounds (21
CFR 500.82 and 500.88).
III. Proposed Conforming Change to 21
CFR Part 514
We are proposing a conforming
change to the language in the
introductory text of § 514.1(b)(7) by
removing the term ‘‘regulatory’’ in the
last sentence to reflect the fact that we
are reserving this term for use with
carcinogenic compounds. (See
discussion in section II.C.)
IV. Legal Authority
Our authority for issuing this
proposed rule is provided by sections
512(b)(1)(G) and (H), 512(d)(1)(F),
512(d)(2), 512(i), 571(a)(2)(A), and
571(b)(1) of the FD&C Act (21 U.S.C.
360b(b)(1)(G) and (H), 360b(d)(1)(F),
360(d)(2), 360b(i), 360ccc(a)(2)(A), and
360ccc(b)(1)). These provisions relate to
the information new animal drug and
conditional approval applicants provide
with respect to proposed tolerances,
withdrawal periods, and practicable
methods, and the process by which FDA
establishes and publishes regulations
setting tolerances for residues of
approved and conditionally approved
new animal drugs. In addition, section
701(a) of the FD&C Act (21 U.S.C.
371(a)) gives FDA general rulemaking
authority to issue regulations for the
efficient enforcement of the FD&C Act.
V. Economic Analysis of Impacts
We have examined the impacts of the
proposed rule under Executive Order
12866, Executive Order 13563, 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 and 13563
direct us to assess all costs and benefits
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). We
believe that this proposed rule is not a
significant regulatory action as defined
by Executive Order 12866.
The Regulatory Flexibility Act
requires us to analyze regulatory options
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74965
that would minimize any significant
impact of a rule on small entities.
Because this proposed rule would not
impose compliance costs on the current
or future sponsors of any approved and
conditionally approved new animal
drugs, we proposed to certify that the
proposed rule would 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
costs and benefits, 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 $146 million,
using the most current (2015) 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.
VI. Paperwork Reduction Act of 1995
We tentatively conclude that this
proposed rule contains no collection of
information. Therefore, clearance by the
Office of Management and Budget under
the Paperwork Reduction Act of 1995 is
not required.
VII. Analysis of Environmental Impact
The Agency has determined under 21
CFR 25.30(i) 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.
VIII. Federalism
We have analyzed this proposed rule
in accordance with the principles set
forth in Executive Order 13132. We
have determined that the proposed rule
does not contain policies that have
substantial direct effects on the States,
on the relationship between the
National Government and the States, or
on the distribution of power and
responsibilities among the various
levels of government. Accordingly, we
conclude that the proposed rule does
not contain policies that have
federalism implications as defined in
the Executive order and, consequently,
a federalism summary impact statement
is not required.
IX. References
The following references are on
display in the Division of Dockets
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Management (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. FDA has verified
the Web site addresses, as of the date
this document publishes in the Federal
Register, but Web sites are subject to
change over time.
1. International Programme on Chemical
Safety, ‘‘Environmental Health Criteria
240, Principals and Methods for the Risk
Assessment of Chemicals in Food,’’
2009. (https://www.who.int/foodsafety/
publications/chemical-food/en/).
Accessed on February 11, 2016.
2. FDA, ‘‘Draft Guidance for Industry #232:
Studies to Evaluate the Safety of
Residues of Veterinary Drugs in Human
Food: General Approach to Establish an
Acute Reference Dose (ARfD), VICH
GL54,’’ (https://www.fda.gov/downloads/
AnimalVeterinary/
GuidanceComplianceEnforcement/
GuidanceforIndustry/UCM448430.pdf),
June 2015. Accessed on February 11,
2016.
List of Subjects
21 CFR Part 514
Administrative practice and
procedure, Animal drugs, Confidential
business information, Reporting and
recordkeeping requirements.
21 CFR Part 556
Animal drugs, Foods.
Therefore, under the Federal Food,
Drug, and Cosmetic Act and under
authority delegated to the Commissioner
of Food and Drugs, it is proposed that
21 CFR chapter I, subchapter E, be
amended as follows:
PART 514—NEW ANIMAL DRUG
APPLICATIONS
1. 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.
§ 514.1
[Amended]
2. In § 514.1(b)(7) introductory text,
remove the word ‘‘regulatory’’ from the
last sentence.
■
mstockstill on DSK3G9T082PROD with PROPOSALS
PART 556—TOLERANCES FOR
RESIDUES OF NEW ANIMAL DRUGS
IN FOOD
3. The authority citation for part 556,
as proposed to be revised on December
5, 2012 (77 FR 72254), continues to read
as follows:
■
Authority: 21 U.S.C. 342, 360b, 360ccc,
371.
4. Amend § 556.3, as proposed to be
added on December 5, 2012 (77 FR
72254), as follows:
■
VerDate Sep<11>2014
17:23 Oct 27, 2016
Jkt 241001
a. Remove the definition of
‘‘Acceptable single-dose intake’’;
■ b. Add, in alphabetical order, a
definition for ‘‘Acute reference dose’’;
■ c. Revise the definitions for ‘‘Marker
residue’’ and ‘‘Not required’’;
■ d. Remove the definition of
‘‘Regulatory method’’; and
■ e. Revise the definitions for
‘‘Tolerance’’ and ‘‘Zero’’.
The revisions and additions read as
follows:
withdrawal period, and any other use
restrictions necessary to ensure that the
proposed use of the drug will be safe.
§ 556.3
22 CFR Part 96
■
Definitions.
*
*
*
*
*
Acute reference dose (ARfD) means an
estimate of the amount of residues
expressed on a body weight basis that
can be ingested in a period of 24 hours
or less without adverse effects or harm
to the health of the human consumer.
*
*
*
*
*
Marker residue means the residue
whose concentration is in a known
relationship to the concentration of total
residue in an edible tissue.
*
*
*
*
*
Not required, in reference to
tolerances in this part, means that at the
time of approval:
(1) No withdrawal period was
necessary for residues of the drug to
deplete to or below the concentrations
considered to be safe, or an adequate
withdrawal period was inherent in the
proposed drug use, and there was a
rapid depletion of residues, so there was
no concern about residues resulting
from misuse or overdosing; or
(2) No withdrawal period was
necessary because the drug was poorly
absorbed or metabolized rapidly so as to
make selection of an analyte impractical
or impossible.
*
*
*
*
*
Tolerance means the maximum
concentration of a marker residue, or
other residue indicated for monitoring,
that can legally remain in a specific
edible tissue of a treated animal.
*
*
*
*
*
Zero, in reference to tolerances in this
part, means any residues detected in the
tissue renders it unsafe.
■ 5. Amend § 556.5, as proposed to be
added on December 5, 2012 (77 FR
72254), by revising paragraph (d) to read
as follows:
§ 556.5
General considerations.
*
*
*
*
*
(d) FDA requires that a drug sponsor
submit a practicable method as part of
their new animal drug application. FDA
uses the practicable method to
determine the quantity of the drug
residues that can safely remain in edible
tissues (i.e., the tolerance), the
PO 00000
Frm 00017
Fmt 4702
Sfmt 4702
Dated: October 21, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016–26043 Filed 10–27–16; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF STATE
[Public Notice: 9772]
RIN 1400–AD91
Intercountry Adoptions
Department of State.
Proposed rule; extension of
comment period.
AGENCY:
ACTION:
The Department of State (the
Department) is extending the period of
time by 15 days for the public to submit
comments on the Proposed Intercountry
Adoption rule, in order to give the
public more time to respond.
DATES: The new comment closing date
for the September 8, 2016, NPRM (FR
Doc No. 2016–20968, 81 FR 62322), is
November 22, 2016.
ADDRESSES:
• Internet: You may view this
Proposed rule and submit your
comments by visiting the
Regulations.gov Web site at
www.regulations.gov, and searching for
docket number DOS–2016–0056.
• Mail or Delivery: You may send
your paper, disk, or CD–ROM
submissions to the following address:
Comments on Proposed rule 22 CFR
part 96, Office of Legal Affairs, Overseas
Citizens Services, U.S. Department of
State, CA/OCS/L, SA–17, Floor 10,
Washington, DC 20522–1710.
• All comments should include the
commenter’s name and the organization
the commenter represents (if
applicable). If the Department is unable
to read your comment for any reason,
the Department might not be able to
consider your comment. Please be
advised that all comments will be
considered public comments and might
be viewed by other commenters;
therefore, do not include any
information you would not wish to be
made public. After the conclusion of the
comment period, the Secretary will
publish a Final rule as expeditiously as
possible in which it will address
relevant public comments.
FOR FURTHER INFORMATION CONTACT:
Technical Information: Trish Maskew,
(202) 485–6024.
SUMMARY:
E:\FR\FM\28OCP1.SGM
28OCP1
Agencies
[Federal Register Volume 81, Number 209 (Friday, October 28, 2016)]
[Proposed Rules]
[Pages 74962-74966]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-26043]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 514 and 556
[Docket No. FDA-2012-N-1067]
RIN 0910-AG17
New Animal Drugs; Updating Tolerances for Residues of New Animal
Drugs in Food
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule; supplemental notice of proposed rulemaking.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or we) is proposing to
amend our 2012 document entitled ``New Animal Drugs; Updating
Tolerances for Residues of New Animal Drugs in Food.'' The document
proposed to revise the animal drug regulations regarding tolerances for
residues of approved and conditionally approved new animal drugs in
food by standardizing, simplifying, and clarifying the determination
standards and codification style. We also proposed to add definitions
for key terms. We are taking this action to more clearly explain our
current thinking about certain provisions of the 2012 document based on
comments from stakeholders, and to more accurately reflect the
rationale FDA relied on in the past to approve certain new animal drugs
without a tolerance. We are reopening the comment period only with
respect to the specific issues identified in this supplemental proposed
rule.
DATES: Submit either electronic or written comments on this proposed
rule by December 27, 2016.
ADDRESSES: You may submit comments as follows:
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 Submission
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Division of
Dockets Management, 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-2012-N-1067 for this proposed rulemaking. Received comments will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
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 Division of Dockets Management. 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.fda.gov/regulatoryinformation/dockets/default.htm.
Docket: For access to the docket to read background documents 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 Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Dong Yan, Center for Veterinary
Medicine (HFV-151), Food and Drug Administration, 7500 Standish Pl.,
Rockville, MD 20855, 240-402-0825, dong.yan@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
[[Page 74963]]
Table of Contents
Executive Summary
Purpose and Coverage of the Supplemental Notice of Proposed
Rulemaking
Summary of the Major Provisions of the Supplemental Notice of
Proposed Rulemaking
I. Background
A. Introduction
B. Comments to the 2012 Proposed Rule for Updating Tolerances
for Residues of New Animal Drugs in Food
II. Proposed Revisions to Subpart A--General Provisions
A. Analytical Method
B. Proposed Revisions to Definitions (Proposed Sec. 556.3)
C. Proposed Revisions to General Considerations (Proposed Sec.
556.5)
III. Proposed Conforming Change to 21 CFR Part 514
IV. Legal Authority
V. Economic Analysis of Impacts
VI. Paperwork Reduction Act of 1995
VII. Analysis of Environmental Impact
VIII. Federalism
IX. References
Executive Summary
Purpose and Coverage of the Supplemental Notice of Proposed Rulemaking
We previously proposed to revise the animal drug regulations
regarding tolerances for residues of approved and conditionally
approved new animal drugs in food. In addition to proposing to
standardize, simplify, and clarify the standards of determination and
codification style for tolerances, we proposed a new definition
section. In this document, we are proposing to revise or remove some of
the previously proposed definitions, taking into account comments we
received that have led us to clarify our current thinking, and to more
accurately reflect the rationale FDA relied on in the past to approve
certain new animal drugs without a tolerance.
Summary of the Major Provisions of the Supplemental Notice of Proposed
Rulemaking
The previously proposed rule (2012 proposed rule) did not
adequately explain our current view that methods other than the
``regulatory method'' derived from the method submitted by a sponsor as
part of the new animal drug application can be used to determine the
quantity of residue in edible tissues for surveillance and enforcement
purposes. Therefore, we are removing the proposed definition for
``regulatory method'' and are reserving the term for use with
carcinogenic compounds. We are also removing the use of this term from
proposed Sec. 556.5(d) (21 CFR 556.5(d)). We are proposing to revise
portions of the 2012 proposed rule to better align the proposed rule
with our current thinking and practice that an analytical method other
than the practicable method(s) submitted by the sponsor as part of the
new animal drug application can be used for surveillance and
enforcement purposes for non-carcinogenic compounds, as long as the
performance criteria of that method are comparable to those of the
practicable method. However, as described in section II.C, we are not
proposing similar changes to the regulations concerning carcinogenic
compounds because our current interpretation of the relevant provisions
in the Federal Food, Drug, and Cosmetic Act (the FD&C Act) is that,
unlike for non-carcinogenic compounds, the regulatory method prescribed
in the approval of the new animal drug must be used for surveillance
and enforcement purposes for carcinogenic compounds.
We are also revising the proposed definitions for ``marker
residue'', ``tolerance'', ``not required'', and ``zero''. We are
removing the definition for ``acceptable single-dose intake'' and
adding a definition for ``acute reference dose''.
Table of Abbreviations and Acronyms
------------------------------------------------------------------------
Abbreviation/acronym What it means
------------------------------------------------------------------------
ARfD......................................... Acute reference dose.
ASDI......................................... Acceptable single-dose
intake.
CFR.......................................... Code of Federal
Regulations.
CVM.......................................... Center for Veterinary
Medicine.
FDA.......................................... U.S. Food and Drug
Administration.
FD&C Act..................................... Federal Food, Drug, and
Cosmetic Act.
JECFA........................................ World Health Organization/
Food and Agriculture
Organization of the
United Nations Joint
Expert Committee on Food
Additives.
VICH......................................... International Cooperation
on Harmonisation of
Technical Requirements
for Registration of
Veterinary Medicinal
Products.
------------------------------------------------------------------------
I. Background
A. Introduction
In the Federal Register of December 5, 2012 (77 FR 72254), we
issued a document to revise part 556 (21 CFR part 556) by standardizing
and simplifying the codification style, revising the general
considerations section, adding a scope section, and adding a definition
section to define key terms used in the part. The definition section
was proposed to include the terms used by FDA in the determination of
tolerances. Some of the terms had been used previously in part 556, but
never defined, and some terminology that had been used was outdated or
resulted in confusion to users of the part. We proposed a general
considerations section (proposed Sec. 556.5) to provide additional
information and clarification for the tolerances listed in proposed
subpart B. We are issuing this supplemental notice of proposed
rulemaking to revise the proposed changes to part 556 to align with our
current thinking.
B. Comments to the 2012 Proposed Rule for Updating Tolerances for
Residues of New Animal Drugs in Food
We received several stakeholder comments to the proposed rule
including a comment that requests clarification on the proposed
definition for ``regulatory method'' and on the use of the term in
proposed Sec. 556.5(d), which stated that FDA requires that a drug
sponsor develop a regulatory method to measure drug residues in edible
tissues of approved target species. This comment notes that a
regulatory method has historically been used to refer to the ``required
determinative and confirmatory procedures for regulatory surveillance
of residue concentrations in meat products entering the food supply for
comparison to the tolerance post-commercialization of the product.''
The comment also states the context of the proposal appears to be the
method(s) used to collect data to support the setting of the tolerances
preapproval. The comment also asks if the proposal implies that
tolerances may be established using
[[Page 74964]]
analytical procedures other than the determinative procedure. In
addition, the comment states it should be clarified if regulatory
method is referring to method(s) used preapproval for setting the
tolerance versus a finite method(s) used for determining post-
commercialization residue to compare to the tolerance.
We realize that the term ``regulatory method'' proposed in Sec.
556.3 and used in proposed Sec. 556.5(d) has caused some confusion. As
a result of the comments, we are taking this opportunity to better
explain our current thinking about analytical methods used to determine
residue levels in tissues for new animal drugs intended for use in
food-producing animals.
II. Proposed Revisions to Subpart A--General Provisions
A. Analytical Method
An analytical method other than the practicable method can be used
for surveillance and enforcement purposes for non-carcinogenic
compounds, as long as the performance criteria (e.g., sensitivity,
specificity, accuracy, and precision) of that method are comparable to
those of the practicable method submitted by the sponsor as part of the
new animal drug application. Such an analytical method would need to
have the same capability as the practicable method to determine the
quantity of the drug residues so that the tolerance, withdrawal period,
or other use restrictions continue to ensure that the use of the drug
will be safe. However, as described in section II.C, for carcinogenic
compounds, the regulatory method prescribed in the approval of the new
animal drug must be used for surveillance and enforcement purposes for
carcinogenic compounds (see 21 CFR part 500, subpart E).
FDA establishes tolerances using the practicable method submitted
by a sponsor as part of the new animal drug application as required by
section 512(b)(1)(G) of the FD&C Act (21 U.S.C. 360b(b)(1)(G)). The
practicable method has to meet certain performance criteria, including
evaluation of accuracy, precision, and sensitivity. We use the
practicable method submitted by the sponsor as part of the new animal
drug application to determine the quantity of the drug residues that
can safely remain in edible tissues (i.e., the tolerance), the
withdrawal period, and any other use restrictions necessary to ensure
that the proposed use of the drug will be safe, and make these use
restrictions part of the conditions of approval. These conditions of
use are designed to ensure that the proposed use of the drug will be
safe Sec. 514.1(b)(7) (21 CFR 514.1(b)(7)). In the past, the
practicable method was often used for determining the quantity of
residue in edible tissue when monitoring the food supply. However, as
technologies have evolved, many of the older methods have become
obsolete. In addition, there is an increased reliance on multiresidue
methods in the monitoring of the food supply (i.e., methods that
analyze for a number of different drug residues at the same time). As a
result, we are clarifying that an analytical method other than the
practicable method can be used for surveillance and enforcement
purposes for non-carcinogenic compounds, provided it meets the same
performance criteria as the practicable method to determine the
quantity of the relevant drug residues. Therefore, we are proposing to
revise some of the definitions in proposed Sec. 556.3 of the 2012
proposed rule as well as revise some of the language under ``General
Considerations'' in proposed Sec. 556.5, to more accurately reflect
our current thinking.
B. Proposed Revisions to Definitions (Proposed Sec. 556.3)
In the 2012 proposed rule, we included a section of definitions
(proposed Sec. 556.3). We propose to revise four of the definitions,
remove two definitions, and add a new definition in proposed Sec.
556.3.
In the definition of ``marker residue'', we propose to delete
``selected for assay by the regulatory method'' because we are
reserving the term ``regulatory method'' for use with carcinogenic
compounds (see part 500, subpart E). Also, we propose to delete the
explanatory text that follows the first sentence of the definition
because an explanation of how the tolerance is used is not needed in
this definition. In addition, we are removing the term ``target
tissue'' in the definition and replacing it with ``an edible tissue''.
In the definition of ``not required'', we propose to more
accurately reflect the rationale FDA relied on in the past to approve
certain new animal drugs without a tolerance. Currently, our general
practice is to establish a tolerance for all new animal drugs we
approve.
In the definition of ``tolerance'', we propose to delete the
explanatory text that follows the first sentence of the definition
because an explanation of how the tolerance is used is not needed in
this definition.
In the definition of ``zero'', we propose to delete ``when using a
method of detection prescribed or approved by FDA'' because, as
discussed previously, an analytical method other than the practicable
method can be used for surveillance and enforcement purposes for non-
carcinogenic compounds. The additional proposed revisions to this
definition are intended to clarify the meaning of the term ``zero'' as
used in part 556 so that ``zero'' means any residues detected in the
tissue renders it unsafe.
We propose to remove the definition of ``acceptable single-dose
intake (ASDI)''. See discussion for ``acute reference dose (ARfD)''
further in this section for the explanation.
We propose to remove the definition of ``regulatory method''
because we are reserving the term ``regulatory method'' for use with
carcinogenic compounds, consistent with our current interpretation of
the FD&C Act (see part 500, subpart E).
We propose to add the definition of ``acute reference dose (ARfD)''
to mean ``an estimate of the amount of residues expressed on a body
weight basis that can be ingested in a period of 24 hours or less
without adverse effects or harm to the health of the human consumer.''
ARfD would be used in place of ASDI wherever this term is currently
used in the tolerances listed in subpart B of part 556.
In the 2012 proposed rule, we explained that sometimes the concept
of an ASDI was used to calculate tolerances. We proposed to define the
ASDI as ``the amount of total residue that may safely be consumed in a
single meal. The ASDI may be used to derive the tolerance for residue
of a drug at the injection site where the drug is administered
according to the label.'' The definition of the ASDI was based on the
U.S. Environmental Protection Agency definition of ARfD and chosen, in
part, to provide additional clarity for the veterinary drug health
based guidance value. Since that time, the use of the term ARfD has
been more broadly applied by scientific and regulatory authorities, as
further discussed in this section.
The United States is an active member of the Codex Alimentarius and
the Codex Committee for Residues of Veterinary Drugs in Food, which
rely on the World Health Organization/Food and Agriculture Organization
of the United Nations Joint Expert Committee on Food Additives (JECFA)
for scientific advice. The JECFA uses the guidance Environmental Health
Criteria (EHC) 240, Principles and Methods for the Risk Assessment of
Chemicals in Food in its evaluations (Ref. 1). This guidance defines
and discusses the term ARfD. More importantly for FDA, the
[[Page 74965]]
International Cooperation on Harmonisation of Technical Requirements
for Registration of Veterinary Medicinal Products (VICH) has also
developed guidelines that discuss the ARfD. The United States is a
member of VICH and adopts finalized VICH guidelines for technical
requirements for new animal drug approvals in the United States. On
June 1, 2015 (80 FR 31041), we announced a draft guidance (Guidance for
Industry #232 (VICH GL54)) entitled ``Studies to Evaluate the Safety of
Residues of Veterinary Drugs in Human Food: General Approach to
Establish an Acute Reference Dose (ARfD)'', in which the term ``acute
reference dose (ARfD)'' is used to describe the same concept as the
2012 proposed definition of ASDI (Ref. 2). There are no fundamental
differences between the meaning of ASDI and ARfD.
We consider it appropriate to propose using the VICH definition of
ARfD to replace the 2012 proposed definition of ASDI. The ARfD may be
used in the same manner as the ASDI, which is to derive the tolerance
for residues of a drug at an injection site where the drug is
administered according to the label, or to derive the tolerance for
residues of a drug in other edible tissues as a result of concern for
the acute toxicity of the residues of the veterinary drug.
C. Proposed Revisions to General Considerations (Proposed Sec. 556.5)
We propose to revise proposed Sec. 556.5(d) to align with our
current thinking. In addition, we propose to remove the term
``regulatory method'' from this provision because we are reserving this
term for use with carcinogenic compounds (part 500, subpart E).
Although the proposed revisions would clarify that an analytical
method other than the practicable method may be used for surveillance
and enforcement purposes for residue levels of non-carcinogenic animal
drugs, with regard to approved carcinogenic compounds, our current
interpretation of the relevant provisions of the FD&C Act is that it
requires that a regulatory method be prescribed for such a compound and
used for surveillance and enforcement purposes. Under the Delaney
Clause, section 512(d)(1)(I) of the FD&C Act, FDA cannot approve an
application for a new animal drug if it is found to induce cancer when
ingested by humans or animals. An exception to this provision, referred
to as the DES (diethylstilbestrol) Proviso, allows for the approval of
a carcinogenic compound if FDA finds that, under the approved
conditions of use, the drug will not adversely affect treated animals
and no residue of the drug will be found (by methods of examination
prescribed or approved by the Secretary by regulations) (emphasis
added) in any food for human consumption derived from the treated
animals (see section 512(d)(1)(I)(i) and (ii) of the FD&C Act). FDA has
issued regulations defining the operational definition of no residue
and regulatory method for purposes of measuring carcinogenic compounds
(21 CFR 500.82 and 500.88).
III. Proposed Conforming Change to 21 CFR Part 514
We are proposing a conforming change to the language in the
introductory text of Sec. 514.1(b)(7) by removing the term
``regulatory'' in the last sentence to reflect the fact that we are
reserving this term for use with carcinogenic compounds. (See
discussion in section II.C.)
IV. Legal Authority
Our authority for issuing this proposed rule is provided by
sections 512(b)(1)(G) and (H), 512(d)(1)(F), 512(d)(2), 512(i),
571(a)(2)(A), and 571(b)(1) of the FD&C Act (21 U.S.C. 360b(b)(1)(G)
and (H), 360b(d)(1)(F), 360(d)(2), 360b(i), 360ccc(a)(2)(A), and
360ccc(b)(1)). These provisions relate to the information new animal
drug and conditional approval applicants provide with respect to
proposed tolerances, withdrawal periods, and practicable methods, and
the process by which FDA establishes and publishes regulations setting
tolerances for residues of approved and conditionally approved new
animal drugs. In addition, section 701(a) of the FD&C Act (21 U.S.C.
371(a)) gives FDA general rulemaking authority to issue regulations for
the efficient enforcement of the FD&C Act.
V. Economic Analysis of Impacts
We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, 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 and 13563 direct us to assess all costs
and benefits 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). We
believe that this proposed rule is not a significant regulatory action
as defined by Executive Order 12866.
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because this proposed rule would not impose compliance costs
on the current or future sponsors of any approved and conditionally
approved new animal drugs, we proposed to certify that the proposed
rule would 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 costs and benefits, 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 $146 million, using the most current (2015) 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.
VI. Paperwork Reduction Act of 1995
We tentatively conclude that this proposed rule contains no
collection of information. Therefore, clearance by the Office of
Management and Budget under the Paperwork Reduction Act of 1995 is not
required.
VII. Analysis of Environmental Impact
The Agency has determined under 21 CFR 25.30(i) 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.
VIII. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
the proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
we conclude that the proposed rule does not contain policies that have
federalism implications as defined in the Executive order and,
consequently, a federalism summary impact statement is not required.
IX. References
The following references are on display in the Division of Dockets
[[Page 74966]]
Management (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. FDA has
verified the Web site addresses, as of the date this document publishes
in the Federal Register, but Web sites are subject to change over time.
1. International Programme on Chemical Safety, ``Environmental
Health Criteria 240, Principals and Methods for the Risk Assessment
of Chemicals in Food,'' 2009. (https://www.who.int/foodsafety/publications/chemical-food/en/). Accessed on February 11, 2016.
2. FDA, ``Draft Guidance for Industry #232: Studies to Evaluate the
Safety of Residues of Veterinary Drugs in Human Food: General
Approach to Establish an Acute Reference Dose (ARfD), VICH GL54,''
(https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM448430.pdf),
June 2015. Accessed on February 11, 2016.
List of Subjects
21 CFR Part 514
Administrative practice and procedure, Animal drugs, Confidential
business information, Reporting and recordkeeping requirements.
21 CFR Part 556
Animal drugs, Foods.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR chapter I, subchapter E, be amended as follows:
PART 514--NEW ANIMAL DRUG APPLICATIONS
0
1. 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.
Sec. 514.1 [Amended]
0
2. In Sec. 514.1(b)(7) introductory text, remove the word
``regulatory'' from the last sentence.
PART 556--TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD
0
3. The authority citation for part 556, as proposed to be revised on
December 5, 2012 (77 FR 72254), continues to read as follows:
Authority: 21 U.S.C. 342, 360b, 360ccc, 371.
0
4. Amend Sec. 556.3, as proposed to be added on December 5, 2012 (77
FR 72254), as follows:
0
a. Remove the definition of ``Acceptable single-dose intake'';
0
b. Add, in alphabetical order, a definition for ``Acute reference
dose'';
0
c. Revise the definitions for ``Marker residue'' and ``Not required'';
0
d. Remove the definition of ``Regulatory method''; and
0
e. Revise the definitions for ``Tolerance'' and ``Zero''.
The revisions and additions read as follows:
Sec. 556.3 Definitions.
* * * * *
Acute reference dose (ARfD) means an estimate of the amount of
residues expressed on a body weight basis that can be ingested in a
period of 24 hours or less without adverse effects or harm to the
health of the human consumer.
* * * * *
Marker residue means the residue whose concentration is in a known
relationship to the concentration of total residue in an edible tissue.
* * * * *
Not required, in reference to tolerances in this part, means that
at the time of approval:
(1) No withdrawal period was necessary for residues of the drug to
deplete to or below the concentrations considered to be safe, or an
adequate withdrawal period was inherent in the proposed drug use, and
there was a rapid depletion of residues, so there was no concern about
residues resulting from misuse or overdosing; or
(2) No withdrawal period was necessary because the drug was poorly
absorbed or metabolized rapidly so as to make selection of an analyte
impractical or impossible.
* * * * *
Tolerance means the maximum concentration of a marker residue, or
other residue indicated for monitoring, that can legally remain in a
specific edible tissue of a treated animal.
* * * * *
Zero, in reference to tolerances in this part, means any residues
detected in the tissue renders it unsafe.
0
5. Amend Sec. 556.5, as proposed to be added on December 5, 2012 (77
FR 72254), by revising paragraph (d) to read as follows:
Sec. 556.5 General considerations.
* * * * *
(d) FDA requires that a drug sponsor submit a practicable method as
part of their new animal drug application. FDA uses the practicable
method to determine the quantity of the drug residues that can safely
remain in edible tissues (i.e., the tolerance), the withdrawal period,
and any other use restrictions necessary to ensure that the proposed
use of the drug will be safe.
Dated: October 21, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-26043 Filed 10-27-16; 8:45 am]
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