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.

Proposed Rules Federal Register

2268 

Vol. 76, No. 9 

Thursday, January 13, 2011 

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. 

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 

http://www.regulations.gov/fdmspublic/ 

component/ 

main?main=DocketDetail&d=APHIS2008-0008 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 

http://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 

§ 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 


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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 § 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 § 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 

§ 112.2(a)(3) specify that the license 

number must be shown in labeling as 

‘‘U.S. Veterinary License No. l,’’ or 

‘‘U.S. Vet License No. l,’’ or ‘‘U.S. Vet 

Lic. No. l,’’ and the permit number 

must be shown as ‘‘U.S. Veterinary 

Permit No. l,’’ or ‘‘U.S. Permit No. l,’’ 

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 §§ 112.2(a)(4) and 114.11 

regarding the storage temperature 

recommendation for veterinary biologics 

to prescribe a range of 2 to 8 °C (35 to 

46 °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 °F or stated as 

not over 7 °C or stated as not over 45 

°F or 7 °C.’’ The regulations do not 

prescribe a minimum recommended 

storage temperature for released product 

in distribution channels. Under § 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 °F (2 to 7 °C). Under the proposed 

amendment, the maximum 

recommended storage temperature for 

released product in distribution 

channels would increase to 8 EC (the 

widely recognized standard, and 1 °C 

above the currently prescribed 7 °C), 

and 2 °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 

°C would remain unchanged, and the 

maximum recommended storage 

temperature would be increased to 8 °C 

(1 °C above the currently prescribed 7 

°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 § 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 § 112.2(a)(5) specify that ‘‘full 

instructions for the proper use of the 

product’’ refers to ‘‘vaccination 


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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 §§ 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 § 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 § 112.2(a)(10) to require 

labeling to indicate the presence of nonantibiotic 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 foodproducing 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 § 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 § 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 § 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 § 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, § 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 § 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 § 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 §§ 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 

§ 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 lll. 

• Replacement for label, master label, 

and/or sketch No. lll. 

• Reference to label or master label 

No. lll. 

• Addition to label No. lll. 

• License Application Pending 

lll. 

• Foreign language copy of label No. 

lll. 

We would amend paragraph (d)(4) of 

§ 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 APHISassigned 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 § 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 § 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 


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questions concerning approved labeling 

content. 

Packaging Multiple-Dose Final 

Containers 

We propose to amend the regulations 

in § 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 § 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 § 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 § 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 § 112.7(i) by removing the 

recommendation for annual 

revaccination of cats with feline 

panleukopenia vaccine. 

We are also proposing to amend 

§ 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 § 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 § 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 


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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 § 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 

§ 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 § 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 § 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-todate 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 


srobinson on DSKHWCL6B1PROD with PROPOSALS
2274 Federal Register / Vol. 76, No. 9 / Thursday, January 13, 2011 / Proposed Rules 

1Source: U.S. Census Bureau (2002 Economic 

Census) and SBA. 

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

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 § 103.3, paragraph (d) is revised 

to read as follows: 

§ 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: 


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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. 

§ 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 (noncritical) 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 °C or 35 to 46 

°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 nonantibiotic 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 multipledose 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 § 112.3, paragraph (f)(2) is 

revised to read as follows: 

§ 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 


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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). 

§ 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 § 112.6, paragraph (a) is revised 

to read as follows: 

§ 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. 

§ 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 has been demonstrated in 

pregnant animals, for example, either 

‘‘Do not use in pregnant animals’’ or 

‘‘Unsafe for use in pregnant animals’’ 

would be an appropriate statement for 

products known to be unsafe in 

pregnant animals. For those products 

without safety documentation 

acceptable to APHIS, but not known to 

be unsafe, labeling shall include the 

statement ‘‘This product has not been 

evaluated for safety in pregnant 

animals’’ or an equivalent statement 

acceptable to APHIS. 

(g) * * * 

(4) In the case of biological products 

recommending annual booster 

vaccinations, such recommendations 

must be supported by data acceptable to 


srobinson on DSKHWCL6B1PROD with PROPOSALS
Federal Register / Vol. 76, No. 9 / Thursday, January 13, 2011 / Proposed Rules 2277 

APHIS. In the absence of data 

establishing the need for annual booster 

vaccinations, labeling must bear the 

following statement: ‘‘The need for 

annual booster vaccination has not been 

established for this product; 

consultation with a veterinarian is 

recommended.’’ 

* * * * * 

(j) All but very small final container 

labels for feline panleukopenia vaccines 

shall contain the following 

recommendations for use: 

(1) Killed virus vaccines. Vaccinate 

healthy cats with one dose, except that 

if the animal is less than 12 weeks of 

age, a second dose should be given at 12 

to 16 weeks of age. 

(2) Modified live virus vaccines. 

Vaccinate healthy cats with one dose, 

except that if the animal is less than 12 

weeks of age, a second dose should be 

given at 12 to 16 weeks of age. 

* * * * * 

(m) All labels for autogenous biologics 

must specify the name of the 

microorganism(s) or antigen(s) that they 

contain, and shall bear the following 

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.’’ 

* * * * * 

(o) All labels for conditionally 

licensed products shall bear the 

following statement: ‘‘This product 

license is conditional; efficacy and 

potency have not been fully 

demonstrated.’’ 

* * * * * 

PART 114—PRODUCTION 

REQUIREMENTS FOR BIOLOGICAL 

PRODUCTS 

9. The authority citation for part 114 

continues to read as follows: 

Authority: 21 U.S.C. 151–159; 7 CFR 2.22, 

2.80, and 371.4. 

10. Section 114.11 is revised to read 

as follows: 

§ 114.11 Storage and handling. 

Biological products at licensed 

establishments must be protected at all 

times against improper storage and 

handling. Completed product must be 

kept under refrigeration at 35 to 46 °F 

(2 to 8 °C), unless the inherent nature 

of the product makes storage at different 

temperatures advisable, in which case, 

the proper storage temperature must be 

specified in the filed Outline of 

Production. All biological products to 

be shipped or delivered must be 

securely packed. 

Done in Washington, DC this 7th day of 

January 2011. 

John Ferrell, 

Deputy Under Secretary for Marketing and 

Regulatory Programs. 

[FR Doc. 2011–648 Filed 1–12–11; 8:45 am] 

BILLING CODE 3410–34–P 

NUCLEAR REGULATORY 

COMMISSION 

10 CFR Part 72 

RIN 3150—AI89 

[NRC–2011–0002] 

List of Approved Spent Fuel Storage 

Casks: NUHOMS® HD System Revision 

1 

AGENCY: Nuclear Regulatory 

Commission. 

ACTION: Proposed rule. 

SUMMARY: The U.S. Nuclear Regulatory 

Commission (NRC or the Commission) 

is proposing to amend its spent fuel 

storage cask regulations by revising the 

Transnuclear, Inc. (TN) NUHOMS® HD 

System listing within the ‘‘List of 

Approved Spent Fuel Storage Casks’’ to 

include Amendment No. 1 to Certificate 

of Compliance (CoC) Number 1030. 

Amendment No. 1 would revise the 

definitions for Damaged Fuel Assembly 

and Transfer Operations; add 

definitions for Fuel Class and 

Reconstituted Fuel Assembly; add 

Combustion Engineering 16x16 class 

fuel assemblies as authorized contents; 

reduce the minimum off-normal 

ambient temperature from ¥20 °F to 

¥21 °F; expand the authorized contents 

of the NUHOMS® HD System to include 

pressurized water reactor fuel 

assemblies with control components; 

reduce the minimum initial enrichment 

of fuel assemblies from 1.5 weight 

percent uranium-235 to 0.2 weight 

percent uranium-235; clarify the 

requirements of reconstituted fuel 

assemblies; add requirements to qualify 

metal matrix composite neutron 

absorbers with integral aluminum 

cladding; clarify the requirements for 

neutron absorber tests; delete use of 

nitrogen for draining the water from the 

dry shielded canister (DSC), and allow 

only helium as a cover gas during DSC 

cavity water removal operations; and 

make corresponding changes to the 

technical specifications (TS). 

DATES: Comments on the proposed rule 

must be received on or before February 

14, 2011. 

ADDRESSES: Please include Docket ID 

NRC–2011–0002 in the subject line of 

your comments. For instructions on 

submitting comments and accessing 

documents related to this action, see 

Section I, ‘‘Submitting Comments and 

Accessing Information’’ in the 

SUPPLEMENTARY INFORMATION section of 

this document. You may submit 

comments by any one of the following 

methods. 

Federal Rulemaking Web site: Go to 

http://www.regulations.gov and search 

for documents filed under Docket ID 

NRC–2011–0002. Address questions 

about NRC dockets to Carol Gallagher, 

telephone: 301–492–3668, e-mail: 

Carol.Gallager@nrc.gov. 

Mail comments to: Secretary, U.S. 

Nuclear Regulatory Commission, 

Washington, DC 20555–0001, ATTN: 

Rulemakings and Adjudications Staff. 

E-mail comments to: 

Rulemaking.Comments@nrc.gov. If you 

do not receive a reply e-mail confirming 

that we have received your comments, 

contact us directly at 301–415–1677. 

Hand-deliver comments to: 11555 

Rockville Pike, Rockville, Maryland 

20852, between 7:30 a.m. and 4:15 p.m. 

Federal workdays (Telephone 301–415– 

1677). 

Fax comments to: Secretary, U.S. 

Nuclear Regulatory Commission at 301– 

415–1101. 

FOR FURTHER INFORMATION CONTACT: 

Gregory Trussell, Office of Federal and 

State Materials and Environmental 

Management Programs, U.S. Nuclear 

Regulatory Commission, Washington, 

DC 20555–0001, telephone: 301–415– 

6445, e-mail: Gregory.Trussell@nrc.gov. 

SUPPLEMENTARY INFORMATION: 

Submitting Comments and Accessing 

Information 

Comments submitted in writing or in 

electronic form will be posted on the 

NRC Web site and on the Federal 

Rulemaking Web site, http:// 

www.regulations.gov. Because your 

comments will not be edited to remove 

any identifying or contact information, 

the NRC cautions you against including 

any information in your submission that 

you do not want to be publicly 

disclosed. The NRC requests that any 

party soliciting or aggregating comments 

received from other persons for 

submission to the NRC inform those 

persons that the NRC will not edit their 

comments to remove any identifying or 

contact information, and therefore, they 

should not include any information in 

their comments that they do not want 

publicly disclosed. 

You can access publicly available 

documents related to this document 

using the following methods: 

NRC’s Public Document Room (PDR): 

The public may examine and have 


srobinson on DSKHWCL6B1PROD with PROPOSALS