Viruses, Serums, Toxins, and Analogous Products; Packaging and Labeling, 2268-2277 [2011-648]

Agencies

• DEPARTMENT OF AGRICULTURE
• Animal and Plant Health Inspection Service

[Federal Register Volume 76, Number 9 (Thursday, January 13, 2011)]
[Proposed Rules]
[Pages 2268-2277]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-648]


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Proposed Rules
                                                Federal Register
________________________________________________________________________

This section of the FEDERAL REGISTER contains notices to the public of 
the proposed issuance of rules and regulations. The purpose of these 
notices is to give interested persons an opportunity to participate in 
the rule making prior to the adoption of the final rules.

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Federal Register / Vol. 76, No. 9 / Thursday, January 13, 2011 / 
Proposed Rules

[[Page 2268]]



DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Parts 103, 112, and 114

[Docket No. APHIS-2008-0008]
RIN 0579-AD19


Viruses, Serums, Toxins, and Analogous Products; Packaging and 
Labeling

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Proposed rule.

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SUMMARY: We are proposing to amend the Virus-Serum-Toxin Act 
regulations regarding the packaging and labeling of veterinary 
biological products to provide for the use of an abbreviated true name 
on small final container labeling for veterinary biologics; require 
labeling to bear a consumer contact telephone number; change the format 
used to show the establishment or permit number on labeling and require 
such labeling to show the product code number; change the storage 
temperature recommended in labeling for veterinary biologics; require 
vaccination and revaccination recommendations in labeling to be 
consistent with licensing data; require labeling information placed on 
carton tray covers to appear on the outside-face of the tray cover; 
remove the restriction requiring multiple-dose final containers of 
veterinary biologics to be packaged in individual cartons; require 
labeling for bovine virus diarrhea vaccine containing modified live 
virus to bear a statement warning against use in pregnant animals; 
reduce the number of copies of each finished final container label, 
carton label, or enclosure required to be submitted for review and 
approval; require labeling for autogenous biologics to specify the 
microorganism(s) and/or antigen(s) they contain; and require labeling 
for conditionally licensed veterinary biologics to bear a statement 
concerning efficacy and potency requirements. In addition, we also 
propose to amend the regulations concerning the number of labels or 
label sketches for experimental products required to be submitted for 
review and approval, and the recommended storage temperature for 
veterinary biologics at licensed establishments. These proposed 
amendments are necessary in order to update and clarify labeling 
requirements and ensure that information provided in labeling is 
accurate with regard to the expected performance of the product.

DATES: We will consider all comments that we receive on or before March 
14, 2011.

ADDRESSES: You may submit comments by either of the following methods:
     Federal eRulemaking Portal: Go to https://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=APHIS-2008-0008 to submit or view comments and 
to view supporting and related materials available electronically.
     Postal Mail/Commercial Delivery: Please send one copy of 
your comment to Docket No. APHIS-2008-0008, Regulatory Analysis and 
Development, PPD, APHIS, Station 3A-03.8, 4700 River Road Unit 118, 
Riverdale, MD 20737-1238. Please state that your comment refers to 
Docket No. APHIS-2008-0008.
    Reading Room: You may read any comments that we receive on this 
docket in our reading room. The reading room is located in room 1141 of 
the USDA South Building, 14th Street and Independence Avenue, SW., 
Washington, DC. Normal reading room hours are 8 a.m. to 4:30 p.m., 
Monday through Friday, except holidays. To be sure someone is there to 
help you, please call (202) 690-2817 before coming.
    Other Information: Additional information about APHIS and its 
programs is available on the Internet at https://www.aphis.usda.gov.

FOR FURTHER INFORMATION CONTACT: Dr. Albert P. Morgan, Chief of 
Operational Support, Center for Veterinary Biologics, Licensing and 
Policy Development, VS, APHIS, 4700 River Road Unit 148, Riverdale, MD 
20737-1231; (301) 734-8245.

SUPPLEMENTARY INFORMATION:

Background

    Under the Virus-Serum-Toxin Act (the Act, 21 U.S.C. 151-159) and 
regulations issued under the Act, the Animal and Plant Health 
Inspection Service (APHIS) grants licenses or permits for biological 
products which are pure, safe, potent, and efficacious when used 
according to label instructions. The regulations in 9 CFR part 112, 
``Packaging and Labeling'' (referred to below as the regulations), 
prescribe requirements for the packaging and labeling of veterinary 
biological products including requirements applicable to final 
container labels, carton labels, and enclosures. The main purpose of 
the regulations in part 112 is to regulate the packaging and labeling 
of veterinary biologics in a comprehensive manner, which includes 
ensuring that labeling provides adequate instructions for the proper 
use of the product, including vaccination schedules, warnings, and 
cautions. Complete labeling (either on the product or accompanying the 
product) must be reviewed and approved by APHIS in accordance with the 
regulations in part 112 prior to their use.
    Although the science of immunology and our understanding of how 
veterinary biologics work have advanced substantially in recent years, 
communicating such information to consumers by way of updated labeling 
claims, cautions, and warnings has not kept pace. Therefore, we are 
proposing to amend several sections of the regulations in part 112 to 
make veterinary biologics labeling requirements more consistent with 
current science and veterinary practice.

True Name, Abbreviated True Name, Functional/Chemical Name

    We are proposing to amend Sec.  112.2(a)(1) of the regulations 
concerning required labeling information to provide for the use of an 
abbreviated true name on labeling for small final containers of 
veterinary biologics. Currently, the regulations require the true name 
shown in the product license or permit under which a product is 
imported to be used in veterinary biologics labeling. However, due to 
the small size of the labeling used on small final containers of some 
veterinary biologics and the amount of label surface that must be 
devoted to

[[Page 2269]]

emphasizing the true name of the product, there may not be adequate 
remaining space on such labeling for the legible presentation of other 
required information. Under the proposed amendment, when issuing or 
reissuing licenses for veterinary biologics, APHIS would assign 
abbreviated true names-shortened forms of the true name of the product 
shown in the product license/permit--which may be used in place of the 
long form of the true name on labeling for small final containers of 
veterinary biologics. While abbreviated true names may be used on small 
final container labels, the complete true name along with the 
abbreviation for such true name would be shown on carton labels and 
enclosures. Thus, the association between the true name of the product 
and its abbreviated true name would be readily apparent to consumers, 
veterinarians, and others who utilize veterinary biological products. 
The proposed change would mean that a greater proportion of the (small) 
container label surface may be used to improve the presentation and 
legibility of other required information. The proposed amendment also 
would clarify in this section the requirements for showing the true 
name of the product and/or a functional or chemical name for the 
reagent on labeling for cartons, and containers of interchangeable 
(non-critical) reagents included in diagnostic test kits. Carton or box 
labeling for diagnostic test kits is required to show the true name of 
the test kit as it appears on the product license or permit under which 
such kit is imported; labeling for containers of interchangeable 
reagents included in test kits may show the functional and/or chemical 
name of such reagent(s). The proposed change would facilitate the use 
of a single lot of such interchangeable reagent in a variety of test 
kit configurations.

Consumer Contact Telephone Number

    We are proposing to amend the regulations in Sec.  112.2(a)(2) to 
require labeling for veterinary biologics to bear a telephone number 
that consumers may use to contact the licensee or permittee to report 
adverse events or other unfavorable experiences associated with the use 
of such products. Currently, veterinary biologics labeling is not 
required to bear a telephone number for reporting adverse experiences 
to APHIS and/or the licensee or permittee. In the absence of 
immediately available contact information for reporting such adverse 
experiences, the probability of harm to animals and hazards to humans 
posed by the use of veterinary biologics may increase. The addition to 
veterinary biologics labeling of a telephone number that consumers may 
use to report adverse events and other unfavorable experiences to the 
manufacturer and to APHIS would facilitate the reporting of such 
adverse vaccine experiences and help to ensure that the licensee/
permittee is able to initiate appropriate corrective action in a timely 
manner.

Veterinary License/Permit Number and Product Code Number

    In order to better facilitate product identification, we are 
proposing to amend the regulations in Sec.  112.2(a)(3) to: (1) Require 
labeling for veterinary biologics to bear the product code number (PCN) 
that APHIS assigns to such product and communicates to the manufacturer 
when the product license application is submitted, and (2) specify a 
revised format for showing the veterinary establishment license number 
(VLN) or veterinary establishment permit number (VPN) in veterinary 
biologics labeling. The license or permit number would be shown side-
by-side with the product code number using the format VLN/PCN or VPN/
PCN, as applicable. For example, the VLN/PCN relationship for a product 
prepared by veterinary biologics licensee number 100 (VLN 100) under 
product code number 1A34.XX (PCN 1A34.XX) would be shown in labeling 
as: VLN/PCN 100/1A34.XX. Currently, the regulations in Sec.  
112.2(a)(3) specify that the license number must be shown in labeling 
as ``U.S. Veterinary License No. --,'' or ``U.S. Vet License No. --,'' 
or ``U.S. Vet Lic. No. --,'' and the permit number must be shown as 
``U.S. Veterinary Permit No. --,'' or ``U.S. Permit No. --,'' but there 
is no requirement for the PCN to appear in labeling. The true name of 
the product, the veterinary license or permit number, and the product 
serial or lot number, all currently required to be shown in labeling, 
are used for product identification. In most instances, such 
information is sufficient for product identification. However, such 
information may be insufficient if the licensee or permittee prepares 
or distributes two or more products that have the same true name and 
use an overlapping sequence of serial numbers; in those instances, 
consumers may need additional information in order to accurately 
identify a product. The addition of the PCN to veterinary biologics 
labeling would provide that additional piece of information. The side-
by-side presentation of the VLN/VPN and PCN in veterinary biologics 
labeling, along with the true name of the product and its serial or lot 
number, would better facilitate product identification and help to 
ensure the accuracy of information provided to the manufacturer and/or 
APHIS concerning product performance.

Storage Temperature

    We are proposing to amend the regulations in Sec. Sec.  112.2(a)(4) 
and 114.11 regarding the storage temperature recommendation for 
veterinary biologics to prescribe a range of 2 to 8 [deg]C (35 to 46 
[deg]F) as the recommended storage temperature for both released 
serials of veterinary biologics stored in distribution channels and 
completed serials of veterinary biologics stored at a licensed 
establishment. Currently, the regulations provide that the storage 
temperature for veterinary biological product in distribution channels 
should be stated as ``not over 45 [deg]F or stated as not over 7 [deg]C 
or stated as not over 45 [deg]F or 7 [deg]C.'' The regulations do not 
prescribe a minimum recommended storage temperature for released 
product in distribution channels. Under Sec.  114.11 of the 
regulations, completed product stored at licensed establishments should 
be kept under refrigeration at temperatures that may range from 35 to 
45 [deg]F (2 to 7 [deg]C). Under the proposed amendment, the maximum 
recommended storage temperature for released product in distribution 
channels would increase to 8 [Egr]C (the widely recognized standard, 
and 1 [deg]C above the currently prescribed 7 [deg]C), and 2 [deg]C 
would be established as the minimum recommended storage temperature. 
For completed product stored in bulk or final containers at licensed 
establishments, the minimum recommended storage temperature of 2 [deg]C 
would remain unchanged, and the maximum recommended storage temperature 
would be increased to 8 [deg]C (1 [deg]C above the currently prescribed 
7 [deg]C). The proposed amendment would standardize veterinary 
biologics storage temperature recommendations in the regulations and, 
thereby, reduce the likelihood that dissimilar recommendations may 
result in mishandling during storage.

Instructions for Use of the Product

    We propose to amend the regulations in Sec.  112.2 (a)(5) to 
clarify that ``full instructions for the proper use of the product'' 
refers to vaccination schedules, revaccination schedules (if 
necessary), indications for use, target species, recommended age for 
vaccination, vaccination route(s), and product license restrictions 
prescribed by APHIS that have a bearing on product use. Currently, the 
regulations in Sec.  112.2(a)(5) specify that ``full instructions for 
the proper use of the product'' refers to ``vaccination

[[Page 2270]]

schedules, warnings, cautions, and the like.'' Although APHIS has 
always considered indications for use, target species, age of 
vaccination, route of vaccination, and product license restrictions to 
be included under ``full instructions for the proper use of the 
product,'' the fact that such information is not specifically 
identified as ``required'' in the regulations may have caused some 
confusion with regard to interpretation, which resulted in requests for 
clarification from licensees and permittees. The proposed amendment 
would ensure consistency in labeling by setting forth under the 
regulations the minimum information that must be provided under 
instructions for use of the product.

Disposal of Containers and Warnings

    We are proposing to amend the regulations in Sec. Sec.  112.2(a)(7) 
and 112.3(f)(2) to require chemical treatment prior to disposal of 
containers of veterinary biologics containing viable or dangerous 
organisms or viruses. In addition, under Sec.  112.2(a)(7) of the 
regulations, the proposed amendment would require labeling to bear 
statements that: (1) Warn persons who inject themselves with veterinary 
biologics to seek medical attention and, (2) warn against treating 
animals with mixtures of veterinary biologics that are not approved for 
administration as combination products. Currently, the regulations 
require labeling to bear the warning ``Burn this container and all 
unused contents'' if a biological product contains viable or dangerous 
organisms or viruses. At the time the regulation was promulgated, 
disposal of discarded veterinary biologics containers by burning was in 
accordance with existing environmental guidelines. At this time, 
however, environmental guidelines in many States prohibit disposal of 
potentially environmentally harmful materials by burning. The proposed 
amendment would update the regulations by specifying chemical 
inactivation as the method for ensuring that the unused contents of 
vaccine containers are made non-hazardous prior to disposal.
    With regard to the use of unapproved combinations of veterinary 
biologics in the treatment of animals and what constitutes an 
appropriate course of action in the event of accidental self injection 
of a veterinary biologic, the regulations do not currently address 
either topic. In the case of using unapproved combinations of 
veterinary biologics in the treatment of animals, many veterinarians 
(and consumers) have made ``judgment'' decisions to inoculate animals 
using mixtures of two or more veterinary biologics that are not 
approved for administration as combination products. In addition to the 
fact that such mixing of product(s) is not recommended in labeling, 
such off-label use disregards the important consideration that antigen 
interference, a frequent occurrence when administering two or more 
antigens concurrently, may render the combined products ineffective and 
could present a disease and/or safety risk in animals. A label 
statement warning against administering unapproved combinations of 
veterinary biologics to animals would ensure that veterinary 
professionals and consumers have the information necessary to use 
veterinary biologics in a safe and effective manner. We propose to 
require labeling to bear a statement advising users to seek medical 
attention should they accidentally inject themselves with veterinary 
biologics because such products frequently contain chemical compounds 
that may cause serious injury or harm when left untreated. We believe 
that it is prudent to make consumers aware of the possibility of 
serious injury as a result of accidental injection of a veterinary 
biologic, and encourage such persons to seek immediate medical 
attention.

Non-Antibiotic Preservatives

    We are proposing to amend the regulations in Sec.  112.2(a)(10) to 
require labeling to indicate the presence of non-antibiotic 
preservatives (anti-infective substances) added during the preparation 
of veterinary biologics. Currently, the regulations only require 
labeling to disclose the presence of antibiotics added at preservative 
levels during the production process. Such disclosure may help to 
identify, and aid in testing for drug residues that may be present in 
the edible portions of food-producing animals that are treated with 
veterinary biologics. In addition to antibiotic preservatives, many 
veterinary biologics also may contain non-antibiotic preservatives that 
are added during the production process. Non-antibiotic preservatives 
also may cause residues in food, unfavorable reactions in animals, and/
or environmental harm. The proposed amendment would treat non-
antibiotic preservatives added during the production process the same 
as antibiotic preservatives, and require labeling disclosure. 
Antibiotic preservatives used in the reagents that are included in 
diagnostic test kits would be exempted from this labeling requirement 
because they are not administered to animals and would not be expected 
to cause food residues. The proposed amendment would ensure that all 
anti-infective substances with the potential to cause harm would be 
disclosed in labeling.

For Animal Use Only

    We are proposing to amend the regulations in Sec.  112.2(d)(3) to 
provide that carton labels and enclosures for veterinary biologics may 
bear the statement ``For animal use only'' in place of the statement 
``For veterinary use only.'' Currently, the regulations specify that 
veterinary biologics labeling may bear the statement ``For veterinary 
use only'' or an equivalent statement when referring to product that is 
recommended specifically for animals, and not for humans. However, 
``For veterinary use only'' is often confused with the similar 
statement in the regulations, ``Restricted to use by or under the 
direction of a veterinarian,'' which is required to be shown on 
labeling for products that have a restriction on the license specifying 
use by or under the direction of a veterinarian. Typically, special 
knowledge and/or expertise is not required when using veterinary 
biologics labeled for ``animal use only,'' whereas professional 
training and/or knowledge may be required for proper use of veterinary 
biologics that are labeled ``restricted to use by or under the 
direction of a veterinarian.'' For example, veterinary biologics for 
use in animal disease control and eradication and wildlife vaccination 
programs may be restricted to use by or under the direction of a 
veterinarian because of concern about disease spread and/or public 
health implications. The proposed amendment would help to clarify the 
distinction between product recommended for use in animals and product 
that should only be administered by or under the direction of a 
veterinarian.

Special Labels for Export

    We are proposing to amend the regulations in Sec.  112.2(e) 
pertaining to the approval of special labels for use on biological 
products to be exported to a foreign country to specify that when the 
labeling requirements of a foreign country conflict with the 
requirements prescribed in the regulations in 9 CFR part 112, such 
request for the approval of special labeling for use on product to be 
exported must be accompanied by a signed document issued by the 
appropriate regulatory official of the importing country that affirms 
the need for such special labeling in order to satisfy the country's 
regulatory requirements. As a condition for the approval, we would 
specify that such

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special labeling may not contain false or misleading information. 
Currently, the regulations provide for the approval of special labels 
for use on biological products for export to a country in which 
labeling requirements conflict with the requirements of the United 
States; however, the regulations do not prescribe the requirements for 
obtaining approval of such special labeling. The proposed amendment 
would clarify the procedure for obtaining approval of special labeling 
for veterinary biological product for export.

Carton Tray Covers

    We are proposing to amend the regulations in Sec.  112.2(f) to 
specify that when carton tray covers are used to show required labeling 
information concerning veterinary biologics, all such information 
should appear on the outer face of the tray cover where it can be read 
without opening the carton. Currently, the use of carton tray covers to 
show required labeling information is not addressed under the 
regulations concerning packaging and labeling. However, carton tray 
covers have come to be extensively used in the packaging of diagnostic 
test kits. Frequently, such tray covers may be used for the 
presentation of required labeling information; and some firms have been 
placing required information on both the outer and inner faces of the 
tray covers. In such situations, information on the inner face of the 
tray cover cannot be read by the consumer because of its placement. The 
proposed change would ensure that required labeling information shown 
on carton tray covers is presented in a manner that is accessible to 
the consumer and consistent with the requirements in the regulations 
that pertain to other labeling media.

Minor Label Changes

    We are proposing to amend the regulations in Sec.  112.5(c)(2) to 
specify additional minor changes that may be made to labeling for 
products with approved labels or master labels without prior approval 
from APHIS. The minor label changes that may be made include changes to 
labeling background color that do not affect legibility of the label; 
changing the telephone number used to contact the licensee or 
permittee; changing or revising an e-mail or Web site address; changing 
the name and/or address of a distributor; or adding, revising, or 
repositioning universal product code bars or other inventory control 
numbers. Changes to the name and/or address of the licensee or 
permittee and changes to the Veterinary License Number or Veterinary 
Permit Number that are made pursuant to the reissuance of an 
Establishment License or Product Permit by APHIS also would be 
considered minor label changes. Currently, Sec.  112.5 of the 
regulations specifies that labeling for veterinary biological product 
must be submitted to APHIS for review for compliance with the 
regulations and approval in writing prior to use. In Sec.  112.5, 
paragraph (c) provides that certain minor changes may be made in labels 
for products with approved labels or master labels, and the revised 
labels may be used prior to review by APHIS if the specified 
requirements are met. In Sec.  112.5, paragraph (c)(2) provides a 
listing of such minor changes that may be made to approved labels and 
master labels. The proposed amendment would specify additional minor 
changes to labeling that need not be submitted to APHIS for review and 
written approval prior to use and, thereby, help to reduce and/or 
eliminate marketing delays.

Submission of Labels

    We are proposing to amend the regulations in Sec. Sec.  
112.5(d)(1)(iii) and (iv) and 103.3(d) to specify that only two copies 
of each finished final container label, carton label, enclosure, and 
experimental label should be submitted for APHIS review and approval. 
Currently, the regulations require three copies of each finished final 
container label, carton label, enclosure, and experimental label to be 
submitted. The third copy of labeling is no longer needed as the result 
of a restructuring of the Center for Veterinary Biologics.

Designation of Label Specimens

    Currently, the regulations in Sec.  112.5(d)(4) require that the 
reason for, and information relevant to, the submission of labels and 
sketches be added to the bottom of each page of label mounting sheets 
for the purpose of facilitating label review. The designations of label 
specimens are to be presented as:
     Master label dose sizes approved for code ------.
     Replacement for label, master label, and/or sketch No. --
----.
     Reference to label or master label No. ------.
     Addition to label No. ------.
     License Application Pending ------.
     Foreign language copy of label No. ------.
    We would amend paragraph (d)(4) of Sec.  112.5 to make it clear 
that only the applicable designation or designations, and not all of 
them, need to appear at the bottom of the label mounting sheets. In 
addition, we would reduce the number of designations by combining some 
and eliminating others. Specifically, the specimen designations 
``Reference to label or master label No.'' and ``Addition to label 
No.'' would be combined into a single ``Refer to APHIS-assigned label 
number'' designation, and the ``License Application Pending'' and 
``Foreign Language copy of Label No.'' designations would be removed. 
These proposed amendments would clarify the regulations with regard to 
specimen designation and facilitate a more efficient label submission 
and review process.

Foreign Language Labels

    We are proposing to amend the regulations in Sec.  112.5(e) 
pertaining to special requirements for foreign language labels to 
require that an accurate English translation be provided with all 
foreign language labeling submitted for review and approval. The 
proposal also would require that the foreign language text of 
multilingual labeling for a veterinary biological product distributed 
in the United States must be an accurate translation of the approved 
English text. Currently, the regulations in Sec.  112.5(e)(1) and 
(e)(2) provide, respectively, that either the addition of a statement 
affirming the wording of the foreign language label to be a direct 
translation from a corresponding domestic label, or the submission of 
an English version of the foreign language label with an explanation 
for the difference in texts may be used to certify that foreign 
language text in labeling complies with the regulations. Under the 
proposed amendment, the option to either affirm the foreign language 
label to be a direct translation of an approved domestic label or 
explain the difference in the English and foreign language text would 
be removed from the regulations. Instead, all foreign language labels 
would be required to include an accurate English translation and a 
statement affirming the accuracy of such translation that APHIS would 
keep on file.
    The presence of foreign language text in labeling for product 
intended for domestic distribution is not currently addressed in the 
regulations. However, foreign language text and its translation have 
become a domestic labeling issue due to the implementation of 
multilingual labeling by multinational firms that market globally and 
the fact that such foreign language text may not translate word for 
word into English. The proposed amendment would standardize the 
presentation of information in multilingual labeling and help to 
facilitate the timely resolution of

[[Page 2272]]

questions concerning approved labeling content.

Packaging Multiple-Dose Final Containers

    We propose to amend the regulations in Sec.  112.6(a) pertaining to 
the packaging of biological products by removing a requirement which 
specifies that multiple-dose final containers of veterinary biological 
products that require a diluent for administration must be packaged in 
an individual carton with a container of the proper volume of diluent 
for that dose. Currently, the regulations require multiple-dose 
containers of veterinary biologics to be packaged in individual 
containers in order to ensure that vaccine will be used within a 
reasonable time after reconstitution in order to prevent a significant 
loss of vaccine potency. This requirement was promulgated when much 
less was known about the stability of vaccines, and it was assumed that 
vaccine would lose potency after dilution faster than animals could be 
treated. However, advances in vaccine technology, improved husbandry 
practices, and new methods for administering vaccines have made the 
continued imposition of this requirement an unnecessary burden on the 
veterinary biologics industry.

Special Additional Requirements

    Currently, the regulations in Sec.  112.7 provide for labeling 
requirements that are ``additional to'' the labeling requirements 
prescribed elsewhere in 9 CFR part 112. These additional labeling 
requirements are only applicable to products that have characteristics 
which make the ``special requirements'' necessary. Paragraph (f) of 
Sec.  112.7 requires that, unless otherwise authorized in a filed 
Outline of Production, labels for inactivated bacterial products shall 
contain an unqualified recommendation for a repeat dose to accomplish 
primary immunization to be given at an appropriate time interval. 
Similarly, paragraph (i) of that section has the special requirement 
that labels for feline panleukopenia vaccines shall include a 
recommendation for annual revaccination of cats.
    Such recommendations for annual boosters and/or revaccination are 
predicated on the premise that the protective immunity achieved with 
the primary immunization diminishes with time and, in order to ensure 
continued protection, animals must be revaccinated; the typical 
recommendation is to revaccinate annually. Although all veterinary 
biologics must be shown to provide protective immunity prior to the 
issuance of a license, firms have not been required, except for rabies 
vaccines, to provide data to establish the duration of protective 
immunity and/or the need for and frequency of revaccination to maintain 
such immunity. Despite not having demonstrated that revaccination is 
needed, it is now common practice for veterinary biologics labeling to 
recommend annual booster vaccinations for most products. Consequently, 
for products that were licensed without duration of immunity data, the 
need for annual revaccination is uncertain, and may not benefit the 
animal under certain circumstances. In fact, annual revaccination may 
be harmful in some situations such as with administering feline 
panleukopenia vaccine to cats annually. Alternatively, it could be that 
optimal protection of the animal requires that booster vaccinations be 
administered more frequently that on an annual basis.
    In the absence of data, it is difficult or impossible to prescribe 
the appropriate revaccination interval for the animal. Thus, we are 
proposing to amend Sec.  112.7(f) to require annual booster (annual 
revaccination) recommendations in labeling to be supported by data 
acceptable to APHIS. If such data are not available, we would require 
labeling to bear the following statement: ``A specific revaccination 
schedule has not been established for this product; consultation with a 
veterinarian is recommended.'' In keeping with the above proposed 
requirement that annual revaccination recommendations should be based 
on a demonstrated need for same, we would also amend Sec.  112.7(i) by 
removing the recommendation for annual revaccination of cats with 
feline panleukopenia vaccine.
    We are also proposing to amend Sec.  112.7 to require that labeling 
for all modified live and inactivated vaccines for use in mammals bear 
an appropriate statement concerning the use of the product in pregnant 
animals. Currently, the regulations in Sec.  112.7(e) require that 
labeling for (infectious) bovine rhinotracheitis (IBR) vaccine 
containing modified live virus bear the statement: ``Do not use in 
pregnant cows or calves nursing pregnant cows'' unless the vaccine has 
been shown to be safe for use in pregnant cows and has been exempted 
from the labeling requirement by the Administrator. The purpose of the 
warning statement concerning use in pregnant animals is to inform users 
of the risk to the developing fetus should pregnant cows be treated 
with or exposed to IBR vaccine containing modified live virus. We would 
extend the requirement for such a warning statement to bovine virus 
diarrhea vaccine (BVDV) containing modified live virus.
    For IBR vaccine containing modified live virus and BVDV containing 
modified live virus, labeling would have to bear the statement ``Do not 
use in pregnant animals or in calves nursing pregnant animals.'' 
However, the current exemption found in Sec.  112.7(e) that states that 
a vaccine that has been shown by data acceptable to APHIS to be safe 
for use in pregnant animals may be exempted from this label requirement 
would remain. It should be noted that even when an exemption is 
granted, the label would still have to include a statement concerning 
residual risks, i.e.: ``Fetal health risks associated with the 
vaccination of pregnant animals with this vaccine cannot be 
unequivocally determined during clinical trials conducted for 
licensure. Appropriate strategies to address the risks associated with 
vaccine use in pregnant animals should be discussed with a 
veterinarian.''
    In the case of other modified live and inactivated vaccines, we 
would require that the labeling bear a statement that is appropriate to 
the level of safety that has been demonstrated in pregnant animals. For 
example, a statement such as ``Do not use in pregnant animals'' or 
``Unsafe for use in pregnant animals'' would be an appropriate 
statement for a product that scientific evidence has shown to be unsafe 
in pregnant animals. For products that do not have safety documentation 
acceptable to APHIS, but are not known to be unsafe, the labeling would 
have to include the statement ``This product has not been evaluated for 
safety in pregnant animals'' or an equivalent statement that is 
acceptable to APHIS.
    The extension of such a warning statement to labeling for BVDV, and 
the proposal that both IBR vaccine and BVDV bear a residual risk 
statement concerning the reliability of data developed during limited 
clinical trials in pregnant animals would be new requirements. APHIS is 
proposing to require labeling for BVDV containing modified live virus 
to bear this warning in response to reports in the veterinary 
literature showing that vaccination and/or exposure of pregnant cows to 
BVDV represents a risk to the developing fetus similar to that of IBR 
vaccine containing modified live virus. In proposing to require 
labeling for vaccine for use in pregnant animals to bear a residual 
risk safety statement, APHIS is responding to concerns expressed within 
the veterinary community about vaccine

[[Page 2273]]

safety. The proposed amendment acknowledges the safety and risk 
considerations associated with vaccine use and would convey such 
considerations to consumers.
    Currently, the regulations in Sec.  112.7(l) require that all 
labels for autogenous biologics bear the statement ``Potency and 
efficacy of autogenous biologics have not been established. This 
product is prepared for use only by or under the direction of a 
veterinarian or approved specialist,'' but there is no requirement for 
the label to identify the microorganism(s) used in the preparation of 
the product and the animal species for which the product is 
recommended. However, for all other veterinary biologics, the identity 
of the microorganism(s) and/or antigen(s) used in the preparation of 
the product and the species of animal for which it is intended are 
incorporated into the true name and indications for use statement shown 
in the labeling. We would amend Sec.  112.7(l) to require that labeling 
for autogenous biologics identify the microorganism(s) used in its 
preparation, and the species for which it is prepared. This proposed 
change would standardize veterinary biologics labeling requirements 
across product categories.
    The regulations in Sec.  102.6(c) set forth the requirements for 
the issuance of conditional licenses. These requirements include a 
restriction which specifies that ``Labeling for the [conditionally 
licensed] product may be required to contain information on the 
conditional status of the license.'' This restriction prescribes a 
special requirement applicable to labeling for conditionally licensed 
product, and therefore should be included in the packaging and labeling 
requirements specified in 9 CFR part 112. We would amend the 
regulations in Sec.  112.7 by adding a new paragraph (o) to require 
that labeling for all conditionally licensed products must bear the 
statement, ``This product license is conditional, efficacy and/or 
potency requirements have not been completed.'' This proposed 
requirement would ensure that consumers receive clear information 
regarding a product's conditionally licensed status.
    If adopted, veterinary biologics manufacturers would have 3 years 
to bring all of their product labeling into compliance with the rule.

Executive Order 12866 and Regulatory Flexibility Act

    This proposed rule has been determined to be significant for the 
purposes of Executive Order 12866 and, therefore, has been reviewed by 
the Office of Management and Budget.
    For this proposed rule, we have prepared an economic analysis. The 
analysis, which is set out below, provides a cost-benefit analysis, as 
required by Executive Order 12866, as well as an initial regulatory 
flexibility analysis that considers the potential economic effects of 
this proposed rule on small entities, as required by the Regulatory 
Flexibility Act (RFA, 5 U.S.C. 601 et seq.).
    This proposed rule would amend the Virus-Serum-Toxin Act 
regulations regarding the packaging and labeling of veterinary 
biological products to provide for the use of an abbreviated true name 
on small final container labeling for veterinary biologics; require 
labeling to bear a consumer contact telephone number; change the format 
used to show the veterinary biologics establishment or permit number on 
labeling and require such labeling to show the product code number; 
change the storage temperature recommended in labeling for veterinary 
biologics; require vaccination and revaccination recommendations in 
labeling to be consistent with licensing data; require labeling 
information placed on carton tray covers to appear on the outside-face 
of the tray cover; remove the restriction requiring multiple-dose final 
containers of veterinary biologics to be packaged in individual 
cartons; require labeling for bovine virus diarrhea vaccine containing 
modified live virus to bear a statement warning against use in pregnant 
animals; reduce the number of copies of each finished final container 
label, carton label, or enclosure required to be submitted for review 
and approval; require labeling for autogenous biologics to specify the 
microorganism(s) and/or antigen(s) they contain; and require labeling 
for conditionally licensed veterinary biologics to bear a statement 
concerning efficacy and potency requirements. In addition, this 
proposed rule would amend the regulations concerning the number of 
labels or label sketches for experimental products required to be 
submitted for review and approval, and the recommended storage 
temperature for veterinary biologics at licensed establishments. These 
proposed amendments are necessary in order to update and clarify 
labeling requirements and ensure that information provided in labeling 
is accurate with regard to the expected performance of the product.
    The proposed rule is not expected to have a significant economic 
impact on most veterinary biologics manufacturers. There are several 
reasons. First, most manufactures should be able to comply with the 
rule without having to acquire new labeling equipment or new supplies 
of labels; their existing equipment for generating labels, as well as 
their existing inventory of blank labels, should still be usable if the 
proposal is adopted. This is because the proposed rule primarily 
affects the type of information required to be shown on the label, not 
the volume of that information. Since any increase in the volume of 
information required on labels as a result of the rule should be small, 
most manufacturers should be able to continue using their existing 
label equipment and their existing inventory of blank labels. Even 
manufacturers' existing inventory of preprinted labels (based on the 
current label requirements) would still likely be usable under the 
proposal, since it would give manufacturers a total of 3 years to bring 
all their product labeling into compliance with the rule. It is very 
likely, therefore, that most or all manufacturers would be able to 
fully exhaust their existing inventories of preprinted labels before 
the new label requirements became effective.
    Second, the new information that would be required on labels as a 
result of the rule is basic in nature and should be readily available 
from manufacturers' existing records; accordingly, manufacturers' cost 
of obtaining the new information should be negligible, at most.
    Third, manufacturers' cost to prepare the new label prototypes (for 
submission to APHIS) should be minimal, since it is largely an exercise 
in label editing and formatting.
    Finally, any cost increases stemming from the inclusion of the new 
information on labels should be minimal for most manufacturers.
    Benefits of the Proposed Changes: The proposed rule has the 
potential to benefit consumers of veterinary biologic products (e.g., 
farmers, veterinarians, and pet stores) and, ultimately, the animals 
they treat with those products. This is because it ensures that 
consumers have complete and up-to-date instructions for the proper use 
of those products, including vaccination schedules, warnings, and 
cautions. For animal owners, the monetary benefits are difficult to 
estimate, because they would depend on several factors that are 
currently unknown, i.e., the significance, or gravity, of the harm to 
animals that would be avoided with the rule in effect, and the number, 
and value, of animals that would avoid harm with the rule in effect. 
For some animal owners, especially those with large numbers of high 
value animals, the

[[Page 2274]]

potential monetary benefits could be substantial.
    Costs of the Proposed Changes: For the reasons discussed above, 
costs to comply with the rule should be minimal for most manufacturers.

Effects on Small Entities

    The RFA requires agencies to evaluate the potential effects of 
their proposed and final rules on small entities. Section 603 of the 
RFA calls for an agency to prepare and make available for public 
comment an initial regulatory flexibility analysis describing the 
expected impact of a proposed rule on small entities, unless the head 
of the agency certifies that the rule will not, if promulgated, have a 
significant economic impact on a substantial number of small entities. 
The following initial regulatory flexibility analysis is presented in 
order that the public may have the opportunity to offer comments on 
expected small-entity effects of the proposed rule.
    The businesses most directly affected by the proposed rule are the 
approximately 125 U.S. veterinary biologics manufacturers, including 
permittees. We believe that all of these entities would be affected, as 
none is currently in full compliance with the proposed requirements on 
a voluntary basis. However, for the reasons stated above, the proposed 
rule is not expected to have a significant economic impact on most 
veterinary biologics manufacturers.
    The size of the affected manufacturers is unknown. However, it is 
reasonable to assume that most are small in size, under the U.S. Small 
Business Administration's (SBA) standards (13 CFR 121.201). This 
assumption is based on composite data for providers of the same and 
similar services in the U.S. In 2002, there were 296 U.S. 
establishments in the North American Industry Classification System 
(NAICS) 325414, a classification comprised of establishments primarily 
engaged in manufacturing vaccines, toxoids, blood fractions, and 
culture media of plant or animal origin (except diagnostic). Of the 296 
establishments, 285 (or 96 percent) had fewer than 500 employees, the 
SBA's small entity threshold for establishments in that NAICS category. 
Similarly, in 2002, there were 236 U.S. establishments in NAICS 325413, 
a classification comprised of establishments primarily engaged in 
manufacturing in-vitro diagnostic substances, including biological 
substances. Of the 236 establishments, 223 (or 95 percent) had fewer 
than 500 employees, the SBA's small entity threshold for establishments 
in NAICS 325413.\1\
---------------------------------------------------------------------------

    \1\ Source: U.S. Census Bureau (2002 Economic Census) and SBA.
---------------------------------------------------------------------------

    The proposed rule has no mandatory reporting, recordkeeping, or 
other compliance requirements for biologic manufacturers, other than 
the requirement that noncompliant labels would need to be revised and 
submitted to APHIS for review and approval.
    APHIS has not identified any relevant Federal rules which may 
duplicate, overlap, or conflict with this proposed rule.
    Finally, the RFA requires agencies to describe any significant 
alternatives to the proposed rule that accomplish the stated objectives 
of applicable statutes and that minimize any significant economic 
impact of the proposed rule on small entities. One alternative would be 
to leave the regulations unchanged. Leaving the regulations unchanged 
would be unsatisfactory, because it would perpetuate the current 
situation, i.e., one that does not provide full information to users of 
veterinary biologic products. Another alternative would be to require 
that manufacturers show less, or different, information on their 
labels. That alternative was rejected because APHIS considers the 
proposed label information to be of the type, and the minimum, 
necessary to accomplish the rule's objectives. A third alternative 
would be to require that manufacturers bring all their product labeling 
into compliance with the rule immediately, rather than 3 years after 
the rule becomes effective. This third alternative was unacceptable 
because it does not minimize the impact on manufacturers, especially 
those with an inventory of preprinted labels based on the current label 
requirements.
    Notwithstanding the analysis above, APHIS invites public comment on 
the proposed rule's expected economic impact, including any comment on 
the impact for small entities.

Executive Order 12372

    This program/activity is listed in the category of Federal Domestic 
Assistance under No. 10.025 and is subject to Executive Order 12372, 
which requires intergovernmental consultation with State and local 
officials. (See 7 CFR part 3015, subpart V.)

Executive Order 12988

    This proposed rule has been reviewed under Executive Order 12988, 
Civil Justice Reform. It is not intended to have retroactive effect. 
This rule would not preempt any State or local laws, regulations, or 
policies where they are necessary to address local disease conditions 
or eradication programs. However, where safety, efficacy, purity, and 
potency of biological products are concerned, it is the Agency's intent 
to occupy the field. This includes, but is not limited to, the 
regulation of labeling. Under the Act, Congress clearly intended that 
there be national uniformity in the regulation of these products. There 
are no administrative proceedings which must be exhausted prior to a 
judicial challenge to the regulations under this rule.

Paperwork Reduction Act

    This proposed rule contains no new information collection or 
recordkeeping requirements under the Paperwork Reduction Act of 1995 
(44 U.S.C. 3501-3520).

List of Subjects

9 CFR Parts 103 and 114

    Animal biologics, Reporting and recordkeeping requirements.

9 CFR Part 112

    Animal biologics, Exports, Imports, Labeling, Packaging and 
containers, Reporting and recordkeeping requirements.

    Accordingly, we propose to amend 9 CFR parts 103, 112, and 114 as 
follows:

PART 103--EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF 
BIOLOGICAL PRODUCTS PRIOR TO LICENSING

    1. The authority citation for part 103 continues to read as 
follows:

    Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.4.

    2. In Sec.  103.3, paragraph (d) is revised to read as follows:


Sec.  103.3  Shipment of experimental biological products.

* * * * *
    (d) Two copies of labels or label sketches which show the name or 
identification of the product and bear the statement ``Notice! For 
experimental use only-Not For Sale'' or equivalent. Such statement 
shall appear on final container labels, except that it may appear on 
the carton in the case of very small final container labels and 
labeling for diagnostic test kits. The U.S. Veterinary License legend 
shall not appear on such labels; and
* * * * *

PART 112--PACKAGING AND LABELING

    3. The authority citation for part 112 continues to read as 
follows:


[[Page 2275]]


    Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.4.

    4. Section 112.2 is amended as follows:
    a. By revising paragraphs (a)(1), (a)(2), (a)(3), (a)(4), (a)(5), 
(a)(7), (a)(10), (d)(3), (e), and (f) to read as set forth below.
    b. At the end of paragraphs (a)(6) and (a)(9)(iv), by removing the 
semicolon and adding a period in its place.


Sec.  112.2  Final container label, carton label, and enclosure.

    (a) * * *
    (1) The complete true name of the biological product which name 
shall be identical with that shown in the product license under which 
such product is prepared or the permit under which it is imported, 
shall be prominently lettered and placed giving equal emphasis to each 
word composing it. Descriptive terms used in the true name on the 
product license or permit shall also appear. Abbreviations of the 
descriptive terms may be used on the final container label if complete 
descriptive terms appear on the carton label and enclosure. The 
following exceptions are applicable to small final containers, and 
containers of interchangeable reagents included in diagnostic test 
kits:
    (i) For small final containers, an abbreviated true name of the 
biological product, which shall be identical with that shown in the 
product license under which the product is prepared or the permit under 
which it is imported, may be used: Provided, That the complete true 
name of the product must appear on the carton label and enclosures;
    (ii) In addition to the true name of the kit, the functional and/or 
chemical name of the reagent must appear on labeling for small final 
containers of reagents included in diagnostic kits: Provided, That the 
true name is not required on labeling for small final containers of 
interchangeable (non-critical) components of diagnostic kits.
    (2) For biological product prepared in the United States or in a 
foreign country, the name and address of the producer (licensee, or 
subsidiary) or permittee and of the foreign producer, and an 
appropriate consumer contact telephone number: Provided, That in the 
case of a biological product exported from the United States in labeled 
final containers, a consumer contact telephone number is not required.
    (3) The United States Veterinary Biologics Establishment License 
Number (VLN) or the United States Veterinary Biological Product Permit 
Number (VPN), and the Product Code Number (PCN) assigned by the 
Department, which shall be shown only as ``VLN/PCN'' and ``VPN/PCN,'' 
respectively, except that only the VLN or VPN is required on container 
labels of interchangeable (non-critical) components of diagnostic kits.
    (4) Storage temperature recommendation for the biological product 
stated as 2 to 8 [deg]C or 35 to 46 [deg]F, or both.
    (5) Full instructions for the proper use of the product, including 
indications for use, target species, minimum age of administration, 
route of administration, vaccination schedule, product license 
restriction(s) that bear on product use, warnings, cautions, and any 
other vital information for the product's use; except that:
    (i) In the case of very small final container labels or carton, a 
statement as to where such information is to be found, such as ``See 
enclosure for complete directions,'' ``Full directions on carton,'' or 
comparable statement; and,
    (ii) The true name or abbreviated true name, and product code 
number are not required on very small final container labels for 
interchangeable (non-critical) components of diagnostic kits.
* * * * *
    (7) If the product is an injectable biological product, and/or if 
it contains viable or dangerous organisms or viruses, the following 
warning statements shall appear on the labeling as applicable:
    (i) ``Do not mix with other biological products, except as 
specified on this label.''
    (ii) ``In the case of accidental human exposure, contact a 
physician or other health care provider.''
    (iii) ``Inactivate all unused contents prior to disposal.''
* * * * *
    (10) In the case of a product that contains an antibiotic or non-
antibiotic preservative that is added during the production process, 
the statement ``Contains [name of preservative] as a preservative'' or 
an equivalent statement must appear on cartons and enclosures, if used. 
If cartons are not used, such information must appear on the final 
container label. Labels for diagnostic test kits are exempt from the 
antibiotic statement, but must specify non-antibiotic preservatives.
* * * * *
    (d) * * *
    (3) The statement ``For use in animals only'' may appear on the 
carton labels and enclosures for a product to indicate that the product 
is recommended specifically for animals and not for humans.
    (e) When label requirements of a foreign country conflict with the 
requirements as prescribed in this part, special labels may be approved 
by APHIS for use on biological products to be exported to such country 
upon receipt of signed written certification from regulatory officials 
of the importing country that such labeling has been approved by those 
officials, provided that the labeling does not contain information 
which is false or misleading. When laws, regulations, or other 
requirements of foreign countries require exporters of biological 
products prepared in a licensed establishment to furnish official 
certification that such products have been prepared in accordance with 
the Virus-Serum-Toxin Act and regulations issued pursuant to the Act, 
such certification may be made by the Animal and Plant Health 
Inspection Service upon request of the licensee.
    (f) Multiple-dose final containers of liquid biological product and 
carton tray covers showing required labeling information are subject to 
paragraphs (f)(1) and (f)(2) of this section, respectively.
    (1) If a carton label or an enclosure is required to complete the 
labeling for a multiple-dose final container of liquid biological 
product, only one final container shall be packaged in each carton: 
Provided, That if the multiple-dose final container is fully labeled 
without a carton label or enclosure, two or more final containers may 
be packaged in a single carton which shall be considered a shipping 
box. Labels or stickers for shipping boxes shall not contain false or 
misleading information, but need not be submitted to APHIS for 
approval.
    (2) When required labeling information is shown on a carton tray 
cover, it must be printed on the outside face of such tray cover where 
it may be read without opening the carton. The inside face of the tray 
cover may contain information suitable for an enclosure.
* * * * *
    5. In Sec.  112.3, paragraph (f)(2) is revised to read as follows:


Sec.  112.3  Diluent labels.

* * * * *
    (f) * * *
    (2) The biological product is composed of viable or dangerous 
organisms or viruses, the notice, ``Inactivate all unused contents 
prior to disposal.''
* * * * *
    6. Section 112.5 is amended as follows:
    a. By revising paragraphs (c)(2)(ii), (c)(2)(v), (d)(1)(iii), 
(d)(1)(iv), (d)(4), and (e)(1) to read as set forth below and, at

[[Page 2276]]

the end of paragraph (c)(2)(vi), by removing the period and adding a 
semicolon in its place.
    b. By adding new paragraphs (c)(2)(vii) through (c)(2)(x) to read 
as set forth below.
    c. By removing paragraph (e)(2) and redesignating paragraph (e)(3) 
as paragraph (e)(2).


Sec.  112.5  Review and approval of labeling.

* * * * *
    (c) * * *
    (2) * * *
    (ii) Changes in the color of label print or background, provided 
that such a change does not affect the legibility of the label;
* * * * *
    (v) Adding, changing, deleting, or repositioning label control 
numbers, universal product codes, or other inventory control numbers;
* * * * *
    (vii) Changing the telephone contact number;
    (viii) Adding, changing, or deleting an e-mail and/or Web site 
address;
    (ix) Changing the establishment license or permit number assigned 
by APHIS, and/or changing the name and/or address of the manufacturer 
or permittee, provided that such changes are identical to information 
on the current establishment license or permit; and
    (x) Adding or changing the name and/or address of a distributor.
    (d) * * *
    (1) * * *
    (iii) For finished labels, submit two copies of each finished final 
container label, carton label, and enclosure: Provided, That when an 
enclosure is to be used with more than one product, one extra copy 
shall be submitted for each additional product. One copy of each 
finished label will be retained by APHIS. One copy will be stamped and 
returned to the licensee or permittee. Labels to which exceptions are 
taken shall be marked as sketches and handled under paragraph (d)(1)(i) 
of this section.
    (iv) For finished master labels, submit for each product two copies 
each of the enclosure and the labels for the smallest size final 
container and carton. Labels for larger sizes of containers or cartons 
of the same product that are identical, except for physical dimensions, 
need not be submitted. Such labels become eligible for use concurrent 
with the approval of the appropriate finished master label, provided 
that the marketing of larger size final containers is approved in the 
filed Outline of Production, and the appropriate larger sizes of 
containers or cartons are identified on the label mounting sheet. When 
a master label enclosure is to be used with more than one product, one 
extra copy for each additional product shall be submitted. One copy of 
each finished master label will be retained by APHIS. One copy will be 
stamped and returned to the licensee or permittee. Master labels to 
which exception are taken will be marked as sketches and handled under 
paragraph (d)(1)(ii) of this section.
* * * * *
    (4) To appear on the bottom of each page in the lower left hand 
corner, if applicable:
    (i) The dose size(s) to which the master label applies.
    (ii) The APHIS assigned number for the label or sketch to be 
replaced.
    (iii) The APHIS assigned number for the label to be used as a 
reference for reviewing the submitted label.
    (e) * * *
    (1) An accurate English translation must accompany each foreign 
language label submitted for approval. A statement affirming the 
accuracy of the translation must also be included.
* * * * *
    7. In Sec.  112.6, paragraph (a) is revised to read as follows:


Sec.  112.6  Packaging biological products.

    (a) Multiple-dose final containers of a biological product whose 
final container labeling includes all information required under the 
regulations may be packaged one or more per carton with a container(s) 
of the proper volume of diluent, if required, for that dose as 
specified in the filed Outline of Production: Provided, That cartons 
containing more than one final container of product must comply with 
the conditions set forth in paragraphs (c)(1) through (c)(4) of this 
section. Multiple-dose final containers of a product that require a 
carton or enclosure in order to provide all information required under 
the regulations shall be packaged in an individual carton with the 
proper volume of diluent, if required, for that dose as specified in 
the filed Outline of Production.
* * * * *
    8. Section 112.7 is amended as follows:
    a. By redesignating paragraphs (a) through (m) as paragraphs (b) 
through (n), respectively, and by adding new paragraphs (a) and (o) to 
read as set forth below.
    b. By revising newly redesignated paragraphs (f), (j), and (m) to 
read as set forth below.
    c. In newly redesignated paragraph (g), by adding a new paragraph 
(g)(4) to read as set forth below.


Sec.  112.7  Special additional requirements.

* * * * *
    (a) In the case of biological products recommending annual booster 
vaccinations, such recommendations must be supported by data acceptable 
to APHIS. In the absence of data that establishes the need for annual 
booster vaccinations, labeling must bear the following statement: ``The 
need for annual booster vaccinations has not been established for this 
product; consultation with a veterinarian is recommended.''
* * * * *
    (f) Labeling for all products for use in mammals must bear an 
appropriate statement concerning use in pregnant animals:
    (1) For bovine rhinotracheitis vaccine containing modified live 
virus and bovine virus diarrhea vaccine containing modified live virus, 
all labeling, except small final container labels, shall bear the 
following statement: ``Do not use in pregnant animals or in calves 
nursing pregnant animals.'': Provided, That such vaccine which has been 
shown to be safe for use in pregnant animals may be exempted from this 
label requirement by the Administrator. However, if an exemption is 
granted, the label must include the following statement concerning 
residual risk: ``Fetal health risks associated with the vaccination of 
pregnant animals with this vaccine cannot be unequivocally determined 
during clinical trials conducted for licensure. Appropriate strategies 
to address the risks associated with vaccine use in pregnant animals 
should be discussed with a veterinarian.''
    (2) In the case of other modified live and inactivated vaccine, 
labeling shall bear a statement appropriate to the level of safety that