Viruses, Serums, Toxins, and Analogous Products; Single Label Claim for Veterinary Biological Products, 39669-39675 [2015-16898]

Agencies

• DEPARTMENT OF AGRICULTURE
• Animal and Plant Health Inspection Service

[Federal Register Volume 80, Number 132 (Friday, July 10, 2015)]
[Rules and Regulations]
[Pages 39669-39675]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-16898]



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Federal Register / Vol. 80, No. 132 / Friday, July 10, 2015 / Rules 
and Regulations

[[Page 39669]]



DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Part 112

[Docket No. APHIS-2011-0049]
RIN 0579-AD64


Viruses, Serums, Toxins, and Analogous Products; Single Label 
Claim for Veterinary Biological Products

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

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SUMMARY: We are amending the Virus-Serum-Toxin Act regulations to 
provide for the use of a simpler labeling format that would better 
communicate product performance to the user. Under this rulemaking, the 
previous label format, which reflected any of four different levels of 
effectiveness, is replaced with a single, uniform label format. We are 
also requiring biologics licensees to provide a standardized summary, 
with confidential business information removed, of the efficacy and 
safety data submitted to the Animal and Plant Health Inspection Service 
in support of the issuance of a full product license or conditional 
license. A simpler label format, along with publicly available safety 
and efficacy data, will help biologics producers to more clearly 
communicate product performance to their customers.

DATES: Effective September 8, 2015.

FOR FURTHER INFORMATION CONTACT: Dr. Donna Malloy, Operational Support 
Section, Center for Veterinary Biologics, Policy, Evaluation, and 
Licensing, VS, APHIS, 4700 River Road Unit 148, Riverdale, MD 20737-
1231; (301) 851-3426.

SUPPLEMENTARY INFORMATION: 

Background

    The Animal and Plant Health Inspection Service (APHIS) administers 
and enforces the Virus-Serum-Toxin Act, as amended (21 U.S.C. 151-159). 
The regulations issued pursuant to the Act are intended to ensure that 
veterinary biological products 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 biologics. The regulations ensure that labeling provides 
adequate information concerning the proper use and safety of the 
product, including vaccination schedules, warnings, and cautions.
    APHIS guidelines provide examples of label claims that may be used 
to reflect the expected performance of the product, provided that 
appropriate efficacy data has been submitted and approved by APHIS. 
Prior to this rulemaking, the guidelines, contained in APHIS Veterinary 
Services Memorandum No. 800.202 (https://www.aphis.usda.gov/animal_health/vet_biologics/publications/memo_800_202.pdf), described 
performance requirements and allowable indications statements for four 
different levels (tiers) of effectiveness.
    On April 21, 2014, we published in the Federal Register (79 FR 
22048-22051, Docket No. APHIS-2011-0049) a proposal \1\ to amend the 
Virus-Serum-Toxin Act regulations to provide for the use of a simpler 
labeling format than the existing one. Specifically, we proposed to 
replace the previous four-tier label format with a single, uniform 
label format. We also proposed to require biologics licensees to 
provide a standardized summary, with confidential business information 
removed, of the efficacy and safety data submitted to APHIS in support 
of the issuance of a full product license or conditional license. The 
proposed requirements for a simpler label format and the provision of 
publically available safety and efficacy data were intended to help 
biologics producers more clearly communicate product performance to 
their customers.
---------------------------------------------------------------------------

    \1\ To view the proposed rule, its supporting documents, and the 
comments we received, go to https://www.regulations.gov/#!docketDetail;D=APHIS-2011-0049.
---------------------------------------------------------------------------

    We solicited comments concerning our proposal for 60 days ending 
June 20, 2014. We received seven comments by that date. They were from 
veterinary biologics laboratories, trade associations, a veterinarians' 
association, and individuals. They are discussed below by topic.

Labeling Requirements

    One commenter noted that in both the preamble to the April 2014 
proposed rule and the accompanying economic analysis, we stated that 
the removal of the four-tiered efficacy labeling structure will 
simplify our evaluation of efficacy studies by focusing on a basic 
claim of effectiveness, resulting in a reduction of the time required 
for evaluation and a likely reduction in the number of studies being 
found unacceptable. The commenter requested further explanation of how 
those benefits will result from this rulemaking.
    As a result of this rulemaking, APHIS will be able to evaluate 
these studies for product efficacy rather than whether or not the data 
demonstrate a higher efficacy tier or ``stronger'' label claim. For 
example, under the four-tiered efficacy system, if efficacy data is 
submitted to support the claim of ``Prevention of infection,'' the data 
must be analyzed with a very high degree of confidence to determine if 
it meets the criteria of preventing all colonization or replication of 
the challenge organism in vaccinated and challenged animals. This is 
considered an extremely strong claim and would entail a more extensive 
statistical analysis, as compared to a claim of ``Aids in disease 
control,'' for which the data needs to demonstrate that the product 
alleviates disease severity or reduces disease duration. Conducting 
data reviews with the aim of determining whether a product is effective 
rather than how ``strong'' its label claim is will simplify and 
streamline our review process. Fewer studies will be found unacceptable 
because the data will only have to show that the product is efficacious 
rather than having to support a label claim of a particular level of 
strength.
    One commenter stated that the title of the April 2014 proposed 
rule, specifically its reference to single label claims, was 
misleading. The commenter stated that the proposed rule related to

[[Page 39670]]

a single efficacy indications statement rather than a single label 
claim. Label claims, according to the commenter, are numerous and not 
limited to the efficacy/indication statement.
    Throughout this rulemaking, as well as in the Veterinary Services 
Memorandum referred to above, APHIS has used the term ``label claim'' 
to represent the level of efficacy of the product, as demonstrated by 
the manufacturer, based on approved data. Taken in context, the meaning 
of the term should be clear to readers.
    A commenter stated that APHIS should provide for the continued use 
of distinct label statements for various diseases/syndromes, primary 
parameters in the case definition, or other situations in which such 
label statements would be appropriate. According to the commenter, the 
indications statement contained in the April 2014 proposed rule would 
not fit certain cases, such as those where the indication for a 
biological product is to reduce the shedding of an organism or reduce 
viremia.
    We are not making any changes to the rule text based on this 
comment. The proposed text in Sec.  112.2(a)(5) was sufficiently 
flexible to allow the indications statement to be modified to include a 
specific parameter associated with the case definition of a disease 
syndrome. For example, with acceptable data, the indications statement 
could read, ``This product has been shown to be effective for the 
vaccination of healthy swine__ weeks of age or older against the 
respiratory form of porcine reproductive and respiratory syndrome.''
    A commenter stated that the April 2014 proposed rule offered no 
foundation for our conclusion that the change in labels will provide 
clarity for vaccine users. According to the commenter, there is no 
evidence that a significant percentage of the vaccine users will read 
the labels and choose to look up the required data summary of the 
studies on the Web site. The commenter stated that, contrary to what we 
claimed in the preamble to the April 2014 proposed rule, the proposed 
labeling requirements would make labeling more complex rather than 
simpler.
    We disagree with this comment. In our view, providing safety and 
efficacy data, combined with a simpler labeling format, will allow the 
end user to better assess product performance. We developed the 
proposed requirements in cooperation with stakeholders and the public. 
In 2009, APHIS met with representatives of veterinary biologics 
manufacturers and the American Veterinary Medical Association, which 
represents the largest group of consumers of veterinary biologics. We 
were informed that the current labeling indications were confusing and 
did not provide sufficient insight into the actual performance of the 
product. Further, in 2011, APHIS held a public meeting to discuss 
effectiveness indications statements and received additional feedback 
from the public on draft guidelines concerning effectiveness 
indications statements on labels. The proposed labeling requirements, 
therefore, reflect the views of both APHIS and entities and individuals 
potentially affected by this rulemaking.
    In the preamble to the April 2014 proposed rule, we stated that 
products for which efficacy data are no longer available should 
indicate on the label that the data are not available because the 
product was licensed ``x'' years ago. A commenter suggested that the 
required statement should be modified to remove the reference to a year 
or specific date in order to preclude the need to update the label on 
an annual basis.
    We agree with this comment. APHIS guidelines regarding label claims 
will be revised as this final rule is implemented. The new guideline 
regarding products for which efficacy data is no longer available will 
read as follows: ``Original efficacy data is not available because the 
product was licensed in (date).'' This change will preclude the need to 
update the label each year.
    A commenter stated that a common adverse event warning should 
appear on all biologics. The same commenter also recommended that we 
institute an active adverse event reporting structure.
    While those issues are beyond the scope of the current rulemaking, 
APHIS does recognize the need for adverse event warnings and reporting. 
We intend to address the issues in a future rulemaking.
    A commenter stated that in the proposed rule, we did not adequately 
consider the potential impact of the required label changes upon the 
export of currently licensed veterinary biological products. In the 
commenter's view, APHIS must allow the continued use of currently 
approved export labels (containing the tiered claims and establishment 
number) for all products licensed at the time this rule becomes 
effective.
    Requirements for export labels are beyond the scope of the present 
rulemaking. APHIS is open to working with industry and the public 
regarding transition of international labels, as we have done in the 
past.
    A commenter stated that as a logical next step in our effort to 
standardize labeling requirements for biological products, we should 
require standardized pregnant animal language for product labels. The 
commenter offered examples of pregnant animal language that could be 
used on labels.
    This comment is beyond the scope of the present rulemaking.
    A commenter requested more guidance as to the basic efficacy 
threshold for licensure of new products, stating that neither the 
current efficacy thresholds nor the manner in which they are determined 
for novel products was mentioned in the April 2014 proposed rule.
    Our methodology for statistical and scientific review of efficacy 
data will not change under this rulemaking. We will continue to 
evaluate data based on the primary outcome and clinically relevant 
outcomes of the study. Guidance for efficacy studies can be found on 
the Center for Veterinary Biologics home page under ``Biologics 
Regulation and Guidance'' (https://www.aphis.usda.gov/wps/portal/aphis/ourfocus/animalhealth?1dmy&urile=wcm%3apath%3a%2FAPHIS_Content_Library%2FSA_Our_Focus%2FSA_Animal_Health%2FSA_Vet_Biologics).

Implementation of Proposed Requirements

    In the preamble to the April 2014 proposed rule, we indicated that 
for currently licensed products, manufacturers would have to submit a 
standardized summary of efficacy and safety data and the revised labels 
to APHIS within 4 years of the effective date of this final rule. 
Licensees would have the option of requesting an extension for up to 2 
years.
    Some commenters questioned whether we could realistically implement 
the proposed requirements in 4 years without tremendous disruption to 
APHIS operations, the biologics industry, and the consumer. It was also 
suggested that we could be diverted from ongoing review and approval 
activities because instituting the proposed new requirements would 
necessitate that APHIS management and staff perform a number of new 
tasks. Such an additional workload, it was further suggested, may be 
especially problematic at a time when we already may not have adequate 
resources due to budget pressure. One commenter recommended that we 
phase in the requirements over a period of 8 years. In addition, 
commenters requested clarification on how the phase-in of the 
requirements will be approached and communicated to the public, such 
that

[[Page 39671]]

the rollout and public promotions are coordinated.
    We do not agree that the 8-year implementation period recommended 
by one commenter is needed. In our view, a 4-year phase-in of the 
labeling and data summary requirements, with additional extensions of 
up to 2 years allowed under certain conditions, will provide 
manufacturers and consumers with adequate time to adapt to the 
requirements. We further intend to implement the requirements by 
species (i.e. poultry products, then equine products, etc.) in order to 
ease the impact on the industry and end users. Implementing the 
requirements in this manner will also minimize the impact on APHIS 
personnel with respect to ongoing review and approval activities.
    Some commenters noted that on January 13, 2011, APHIS had published 
an earlier proposed rule in the Federal Register (76 FR 2268-2277, 
Docket No. APHIS-2008-0008) that also proposed changes to the labeling 
requirements for veterinary biological products. Commenters recommended 
that APHIS finalize and implement the two rules simultaneously for the 
benefit of industry and for end users, who will be encountering these 
new labels for the first time, and that we coordinate the 
implementation timeline with industry.
    APHIS agrees with commenters that implementing the rules 
concurrently would be advantageous for end users and industry. We 
intend to finalize the rules in as close proximity to one another as 
possible and to coordinate their implementation with industry.

Data Summary Requirements

    Some commenters addressed issues related to the scope of the 
proposed data summary requirement. It was suggested that the April 2014 
proposed rule was not clear as to the studies that will need to be 
summarized and appear on the APHIS Web site. A commenter stated that 
only ``pivotal'' efficacy and safety studies should be included and 
that reference requalification or other studies that do not lead to a 
change in a label claim should not be among those summarized. It was 
also recommended that, for safety summaries, only field safety studies 
should be included, as they are the most clinically relevant.
    We do not agree with these comments. The purpose of the summaries 
is to present efficacy and safety data in a non-confusing manner. 
Efficacy data summaries will include information regarding study design 
and associated raw data used to license the product, and the results of 
each study will be evaluated in terms of statistical and clinical 
relevance to the disease in question. Because each study is unique in 
terms of health status of the animals, environmental conditions, 
challenge model/strain, and other factors, limiting the range of the 
studies in the manner recommended by the commenters could mean that 
relevant efficacy data would not be made available to the public.
    Some commenters raised concerns related to the parameters we listed 
in the preamble to the April 2014 proposed rule for the data summaries. 
These included, among others, the minimum and maximum age of the target 
species; the diversity of target species; the number of animals in the 
study; whether animals are client-owned; the serologic status of 
animals (including presence or absence of maternal antibody when 
appropriate); and dosage, timing, and route of administration. It was 
noted that we do not currently require information on some of these 
items. The issues raised by these commenters are discussed individually 
in the paragraphs that follow.
    Commenters stated that the maximum age of the target species should 
be removed from the list of parameters. It was stated that because 
older animals have better developed immune systems and are more 
resistant to infection, the minimum age utilized in the study is more 
important to the field use of the vaccine than the maximum.
    It was also recommended by one commenter that the term ``diversity 
of target species'' be removed from the list of parameters. The 
commenter stated that the term is vague and, if meant to distinguish 
among categories (e.g., layers vs. broilers, or breeds), it is 
immunologically irrelevant.
    Another commenter stated that the serological status of the animals 
in the study should not be included unless it is relevant to the label 
claim. If that is not the case, according to the commenter, the 
information is not useful.
    We have already noted that efficacy data summaries will need to 
include information regarding study design and associated raw data used 
to license the product. The study parameters listed in the preamble to 
the April 2014 proposed rule, however, were examples rather than 
requirements. Further guidance documents, including but not limited to, 
a users' guide, will be developed by APHIS to provide, among other 
things, additional clarification of the parameters associated with the 
data summaries. These guidance documents, which are discussed in 
greater detail later in this document, will be released by APHIS and 
made available for public review and comment.
    Some commenters expressed concerns that our parameters for the data 
summaries could potentially lead to exposure of confidential business 
information. One commenter stated that clarification was needed that 
the reference to ``dose'' related to the volume and not to the potency 
of the vaccine. The potency of the vaccine reflects antigen content and 
is confidential business information that has been historically 
protected by APHIS, according to the commenter. The same commenter also 
asserted that the case definition and data regarding the concentration 
of the challenge organism should be removed from the list of parameters 
for the same reason. The commenter suggested that the ``strength'' of 
challenge can be assessed by the morbidity/mortality observed in the 
controls versus the vaccinates. Another commenter stated that the 
primary outcome and clinically relevant outcomes of the study used for 
analysis were confidential business information that should not be 
required in the summaries.
    As noted above, the parameters listed in the preamble of the April 
2014 proposed rule were provided as examples only, not as requirements. 
The studies that will be summarized and included on the APHIS Web site 
are those studies that demonstrate product efficacy and safety 
sufficient for product licensure. We will not require the data 
summaries to include case definitions or statistical results of an 
inferential nature (e.g., confidence intervals and p values). Biologics 
licensees will provide a summary of their data, with confidential 
business information removed. Such information will be protected, thus 
preventing competitors from using efficacy and data summaries for 
marketing, promotion, or advertising initiatives. APHIS will provide 
guidance to the industry, in the form of a users' guide and other 
guidance documents, regarding the appropriate use of data summaries for 
use in marketing, promotion, and/or advertising.
    A commenter stated that the proposed rule was unclear about the 
type of explanatory statistical information that will need to be 
included in the data summaries, given that we indicated that the 
summaries will not include statistical information of an inferential 
nature.
    The purpose of the summaries is to present efficacy and safety data 
in a non-confusing manner. Because these data summaries may be read by 
persons with little to no medical/scientific background, some 
statistical data may be confusing to such readers. Additionally, 
including some statistical

[[Page 39672]]

information in the data summaries may, in some cases, raise or lower 
the public's opinion of a given product, which would be contrary to the 
intent of this initiative. However, there are some instances (e.g., 
lung lesions as a primary outcome) where statistical terms may be 
beneficial to the practitioner or other medically trained persons. We 
will require each data summary to include a statement referring the 
reader to consult their veterinarian for interpretation of the data. In 
addition, as noted above, APHIS will provide guidance to the industry 
regarding the use of data summaries for use in marketing, promotion, 
and/or advertising.
    Some commenters noted that the April 2014 proposed rule did not 
include a format for the summaries. It was suggested that there is a 
lack of consistency in how the firms present information and what APHIS 
reviewers consider acceptable and that if customers are reading the 
product summaries on the Web site, this variability could have a large 
effect on the public perception of different companies' products. Given 
that possibility, it was suggested that APHIS should provide 
information on its Web site to educate users on the complex nature of 
efficacy studies, as well as explanatory statistical information, where 
appropriate, related to individual data summaries. Commenters requested 
more information regarding the nature of such materials and stated that 
APHIS should allow input from the regulated industry in the development 
of both the format and content of the summaries and the educational 
materials.
    As indicated in the preamble to the April 2014 proposed rule, given 
the large number of diseases, vaccine types, and efficacy models, it is 
not possible to standardize the study design for all efficacy studies. 
We will, however, seek industry input regarding the development of a 
data summary template and educational guide. These documents will then 
be made available on our Web site in draft form for public comment.

Guidance Documents and Web Site

    Some commenters emphasized the need for a general users' guide or 
other guidance documents to supplement this final rule. It was 
suggested that, among other things, our guidance documents should 
address advertising and promotion of products under the new system. 
Commenters stated that such documents should indicate that the data in 
the summaries is intended to provide information relative to the 
licensure of a product, that comparisons among the products with 
differing experimental models is not scientifically valid, and that we 
preclude manufacturers from making such comparisons in advertising and 
promotion outside of head-to-head studies.
    We agree with these comments and, as noted above, we will release a 
users' guide and other guidance documents as this final rule is being 
implemented, and we will make the documents available on our Web site 
in draft form for public comment. For the purposes of marketing, 
promotion, or advertising, the manufacturers will be allowed to include 
a statement on promotional and advertising material referring the user 
to the APHIS Web site, where additional efficacy and safety data may be 
found. Promotional studies would not be disclosed on the Web site. This 
policy is consistent with previous guidelines and regulations and would 
not confer an advantage to any particular manufacturer.
    A commenter suggested that our Web site should contain a ``click 
through'' requiring a person wanting to access the data summaries to 
``click'' to indicate he or she has read the statements on the 
limitation of data comparisons before accessing the material.
    We will consider this comment as we craft the Web site that will 
house the educational material and efficacy and safety summaries.
    Commenters stated that the Web address allowing users to access the 
data summaries is too long and not user friendly. The commenters 
suggested that the URL should fit on a label and that, in addition, we 
should allow the Web address to be excluded from very small labels.
    We agree with these comments. The new Web address reads as follows: 
productdata.aphis.usda.gov. We will also allow the Web address to be 
excluded from very small labels.

Additional Comments

    A commenter stated that clarification was needed regarding how the 
requirements contained in this final rule would apply to in-vitro 
diagnostics, which are subject to the same restrictions as vaccines and 
other in-vivo products.
    As indicated in the preamble to the April 2014 proposed rule, 
diagnostic products are not covered under this rulemaking. Further, the 
rulemaking is not applicable to allergenic extracts or autogenous 
products.
    Several commenters expressed concern that the economic analysis 
provided with the April 2014 proposed rule underestimated the costs 
associated with the implementation of this rule. The issues raised by 
the commenters are discussed individually in the paragraphs that 
follow.
    One commenter stated that in that economic analysis, we 
significantly underestimated the costs of preparing safety and efficacy 
summaries, which we estimated to be $55 per summary, and product 
labels, which we estimated to be $99 to $500 per label. According to 
the commenter, current preparation of labels involves input and review 
by scientific, commercial, and regulatory staff, preparation of label 
artwork, generation of printing specifications, generation of 
controlled documentation for the label, formal review and approval 
processes, submission to APHIS for approval, and then formal 
implementation into the production process. Another commenter stated 
that the cost estimates provided in the economic analysis to 
demonstrate lack of significant economic impact seem very optimistic, 
particularly the costs of preparing the summaries, as well as the costs 
of development of new labels and product outlines for the entire 
vaccine line.
    We used cost range information for label changes from a model 
developed by The Food and Drug Administration. The model estimates the 
cost of labeling changes in consumer labeling regulations. While not 
directly applicable to veterinary biologics labeling changes, the model 
does include cost range information on various areas pertinent to a 
veterinary biologics label change.
    We agree that label changes go through multiple approval steps. 
However, because the rule does not require any new scientific content, 
changing the text on the label to fit with the rule requirements should 
be much simpler than the comment would imply. The estimates of costs we 
included in the analysis of the proposed rule do include ranges for 
administrative and recordkeeping costs associated with labeling 
changes. Those costs to manufacturers include understanding the 
regulation, determining their responses, tracking the required change 
throughout the labeling change process, and reviewing and updating 
their records of product labels.
    These labeling cost ranges were used in reference to the cost for 
products for which label changes could be coordinated with planned 
label changes that occur in the normal course of business, and only 
included administrative and recordkeeping costs. For label changes that 
cannot be coordinated with planned label changes, we also included 
other types of costs, such as prepress, graphic design, and

[[Page 39673]]

label printing and materials. Those costs are not attributable to the 
regulation if the labeling is coordinated with a planned change. We 
have included additional information on the composition of the costs 
within the economic analysis that accompanies this final rule.
    After considering these comments, we did revise our estimate of the 
cost of preparing a summary. We continue to believe that it will take 
approximately 1 hour to review instructions, search existing data 
sources, gather and maintain the data needed, and complete and review 
the collection of information. The rule does not require any new 
scientific content, and the new summary format requirement is simply a 
repackaging of existing information on a product that has already been 
collected and assembled as part of the initial licensing process. This 
activity will most likely be done by a mid-level manager, who will most 
likely already be very familiar with the product in question, and this 
labor will cost a manufacturer about $55. We do acknowledge, however, 
that there will be some further management review involved. Therefore, 
we are including another one-half hour of management time to our 
estimate of the cost of preparing a summary. The revised estimate is 
$83 per summary.
    A commenter noted that in the preamble to the July 2014 proposed 
rule, we stated that most labels would be replaced in the normal course 
of business regardless of this rule, given the 4- to 6-year 
implementation timeframe. The commenter disagreed, estimating that 
approximately 20 percent of the labels for existing products would be 
replaced as normal practice. The commenter suggested that the number of 
entities that would incur the expenses associated with replacing labels 
as a result of this rulemaking will be far larger than we projected.
    We respectfully disagree. Of the approximately 11,700 active, 
approved labels, 53 percent, or about 6,200, are no more than 4 years 
old, suggesting that a similar number will be replaced in the ordinary 
course of business during the implementation period. We therefore 
considered 53 percent to be an appropriate percentage to use to 
estimate the number of products for which regulatory labeling changes 
can be coordinated with otherwise planned labeling changes.
    One commenter, representing a manufacturer, stated that we did not 
factor in the cost of replacing printing plates for existing labels, 
thereby significantly underestimating the economic burden placed on 
that entity by this rulemaking.
    In the proposed rule, we did not include the cost of conventional 
printing plates. Based on our review of all labels for licensed 
biologics, we concluded that the general practice among manufacturers 
is to use computer-generated labels. However, to be conservative in our 
cost estimates for this final rule, we assume that 5 percent of labels 
are printed using conventional printing plates. Therefore, we added 
cost estimates for conventional printing plates for 5 percent of the 
labeling changes that cannot be coordinated with otherwise planned 
label changes.
    A commenter stated that the posting of quantitative results 
accompanying the studies would be valuable for veterinarians.
    Basic statistical data may be applicable to certain disease 
situations, such as when lesion consolidation is a primary outcome. 
Such data will be presented in terms of the number of animals 
exhibiting (controls) and not exhibiting (vaccinates) clinical signs of 
disease out of the total numbers of animals vaccinated or not 
vaccinated. For safety studies, the number of animals presenting with 
adverse reactions to vaccination out of the total number of animals 
will be included in the data.

Miscellaneous

    In addition to the changes described above that we are making in 
response to the comments we received, we are making an editorial change 
for the sake of clarity. In Sec.  112.2(a)(5) of the April 2014 
proposed rule, we proposed to require an indications statement to read, 
``This product has been shown to be effective for the vaccination of 
healthy animals __ weeks of age or older against __.'' In order to 
clarify that the specific animal species must be included on the label, 
we are amending that sentence to read as follows: ``An indications 
statement to read, ``This product has been shown to be effective for 
the vaccination of healthy (insert name of species) __ weeks of age or 
older against __.''
    Therefore, for the reasons given in the proposed rule and in this 
document, we are adopting the proposed rule as a final rule, with the 
changes discussed in this document.

Executive Orders 12866 and 13563 and Regulatory Flexibility Act

    This final rule has been determined to be not significant for the 
purposes of Executive Order 12866 and, therefore, has not been reviewed 
by the Office of Management and Budget.
    We have prepared an economic analysis for this rule. The economic 
analysis provides a cost-benefit analysis, as required by Executive 
Orders 12866 and 13563, which direct agencies to assess all costs and 
benefits of available regulatory alternatives and, if regulation is 
necessary, to select regulatory approaches that maximize net benefits 
(including potential economic, environmental, public health and safety 
effects, and equity). Executive Order 13563 emphasizes the importance 
of quantifying both costs and benefits, of reducing costs, of 
harmonizing rules, and of promoting flexibility. The economic analysis 
also provides a final regulatory flexibility analysis that examines the 
potential economic effects of this rule on small entities, as required 
by the Regulatory Flexibility Act. The economic analysis is summarized 
below. Copies of the full analysis are available on the Regulations.gov 
Web site (see footnote 1 in this document for a link to 
Regulations.gov) or by contacting the person listed under FOR FURTHER 
INFORMATION CONTACT.
    We are amending the Virus-Serum-Toxin Act regulations to require 
the use of a simpler labeling format. Biologics licensees and 
permittees will also be required to provide a standardized summary of 
the efficacy and safety data.
    This rule will simplify the evaluation of efficacy studies, thereby 
reducing the amount of time required by APHIS to evaluate study data. A 
novel veterinary biological product can generate revenue in the 
neighborhood of $5 to $10 million per year. Increased efficiencies in 
the generation and evaluation of efficacy data should result in fewer 
delays in bringing a product to market. In addition, a simpler label 
may benefit those manufacturers, both large and small, who export their 
products, as foreign manufacturers do not use a tiered approach to 
label claims.
    This rule will affect all veterinary biologics licensees and 
permittees. Currently, there are approximately 100 veterinary 
biological establishments, including permittees. These companies 
produce about 1,900 different products, and there are about 11,700 
active approved labels for veterinary biologics. There were about 3,100 
labels submitted for approval from June 2012 through May 2013, by about 
two-thirds of the companies.
    Costs of the rule for licensees and permittees are not expected to 
be significant, whether the affected entity is small or large. APHIS 
anticipates that the only costs associated with the new labeling format 
will be one-time costs incurred by licensees and permittees in having 
labels for existing licensed

[[Page 39674]]

products reformatted in accordance with the rule. Most biologics 
companies, in the course of normal business, use a just-in-time method 
for producing new labels and readily alter their content. Because the 
label changes due to this rule will only require new text and not a 
label redesign, they are considered minor changes.
    Products that are not yet licensed but are within 6 months of 
licensure at the time these regulations become effective will be 
expected to be fully compliant no later than 1 year after licensure. 
Products that are more than 6 months away from licensure at the time 
these regulations become effective will be expected to be fully 
compliant at the time of licensure. For products that are currently 
licensed, the standardized summary of efficacy and safety data and the 
revised labels will have to be submitted to APHIS within 4 years of the 
time these regulations become effective. APHIS will consider written 
requests to extend the time period for submitting the summaries by an 
additional 2 years if necessary.
    We estimate that, in total, this rule will cost veterinary 
biological establishments between $1.1 million and $4.1 million, with a 
median estimate of about $2.4 million. Costs associated with the rule 
for an individual manufacturer will depend on the extent of the changes 
required, type of printing method used, and whether the label changes 
can be coordinated with planned label changes. All affected 
manufacturers will incur administrative and recordkeeping costs, that 
is, costs associated with understanding the regulation, determining 
responses, tracking the required changes throughout the labeling change 
process, and reviewing and updating their records of product labels. 
For label changes not coordinated with planned label changes, costs 
will also include labor and materials associated with generating the 
new labels, such as prepress, graphic design, and label printing. Those 
costs are not attributable to the regulation if the labeling revisions 
are coordinated with planned changes.
    In many instances manufacturers will not have to produce new 
labeling materials before they would otherwise do so in the normal 
course of business and will only incur additional administrative and 
recordkeeping costs to track the changes. Costs incurred for minor 
label changes that are coordinated with planned label changes are 
estimated to range between $99 and $500 per label. We estimate that 
there are about 6,200 labels associated with about 1,000 products for 
which there will be this type of coordinated change, and the total cost 
is estimated to range between $99,000 and $500,000.
    Costs incurred for minor label changes that cannot be coordinated 
with planned label changes include costs for prepress, graphic design, 
and printing the labels, in addition to administrative and 
recordkeeping activities. We expect that about 5,500 of the active 
labels, associated with about 900 products, will be changed other than 
in conjunction with a planned change. Administrative and recordkeeping 
costs for these label changes are estimated to range between $198 and 
$1,000 per product, or between about $178,000 and $900,000 in total. We 
estimate that at least 95 percent of the products with labels that will 
need to be changed other than in conjunction with a planned change are 
computer generated with no outside design assistance. The internal 
prepress and graphic design labor costs associated with these changes 
are estimated to be between $135 and $743 for each product. The 
material costs for computer generated labels are estimated to be 
between $100 and $275 for each new label. For these label changes, 
production labor and material costs are estimated to range between 
about $638,000 and $2 million.
    To be conservative in our cost estimates, we assume that 5 percent 
of the products with labels that will need to be changed other than in 
conjunction with a planned change are printed using more costly 
conventional printing plates, and the manufacturers of these products 
use external prepress and graphic design consultants. Prepress and 
graphic design labor costs, internal and external, are estimated to be 
between $810 and $5,043 for each product, totaling between about 
$36,000 and $227,000. There is significant variation in the cost of 
conventionally printed labels depending on the printing method. 
Printing material costs for these label changes are estimated to range 
between about $47,000 and $306,000.
    Minor costs may be incurred in producing the standardized summaries 
of efficacy and safety data for currently licensed products within the 
4-year implementation period. We estimate that about 1,700 revised 
summaries will need to be produced as a result of this rule because 
efficacy and safety studies are frequently provided for multiple 
products. The estimated cost will be about $83 per summary, or about 
$141,000 in total.

Executive Order 12372

    This program/activity is listed in the Catalog 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 final rule has been reviewed under Executive Order 12988, 
Civil Justice Reform. It is not intended to have retroactive effect. 
This rule will 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 final rule contains no new information collection or 
recordkeeping requirements under the Paperwork Reduction Act of 1995 
(44 U.S.C. 3501 et seq.).

List of Subjects in 9 CFR Part 112

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

    Accordingly, we are amending 9 CFR part 112 as follows:

PART 112--PACKAGING AND LABELING

0
1. The authority citation for part 112 continues to read as follows:

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


0
2. Section 112.2 is amended as follows:
0
a. In paragraph (a)(5), by adding a new first sentence.
0
b. By adding a new paragraph (a)(9)(v).
    The additions read as follows:


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

    (a) * * *
    (5) An indications statement to read, ``This product has been shown 
to be effective for the vaccination of healthy (insert name of species) 
__ weeks of age or older against __.'' * * *
* * * * *
    (9) * * *
    (v) A statement similar to ``For more information regarding 
efficacy and

[[Page 39675]]

safety data, go to productdata.aphis.usda.gov.
* * * * *

0
3. Section 112.5 is amended as follows:
0
a. In the introductory text, by removing the words ``paragraph (c) of 
this section and under the master label system provided in paragraph 
(d)'' and adding the words ``paragraph (d) of this section and under 
the master label system provided in paragraph (e)'' in their place.
0
b. In paragraph (a), by removing the words ``(https://www.aphis.usda.gov/animal_health/vet_biologics/vb_forms.shtml)'' and 
adding the words ``(productdata.aphis.usda.gov)'' in their place.
0
c. By redesignating paragraphs (b) through (g) as paragraphs (c) 
through (h).
0
d. By adding a new paragraph (b).
0
e. In newly redesignated paragraph (d)(1), by removing the citation 
``Sec.  112.5(d)'' and adding the words ``paragraph (e) of this 
section'' in its place.
0
f. In newly redesignated paragraph (e)(1)(ii), by removing the citation 
``Sec.  112.5(d)(1)(iii)'' and adding the words ``paragraph (e)(1)(iii) 
of this section'' in its place.
0
g. In newly redesignated paragraph (e)(1)(iii), by removing the 
citation ``Sec.  112.5(d)(1)(i)'' and adding the words ``paragraph 
(e)(1)(i) of this section'' in its place.
0
h. In newly redesignated paragraph (e)(1)(iv), by removing the citation 
``Sec.  112.5(d)(1)(ii)'' and adding the words ``paragraph (e)(1)(ii) 
of this section'' in its place.
0
i. In newly redesignated paragraph (h), by removing the citation 
``Sec.  112.5(c)'' and adding the words ``paragraph (d) of this 
section'' in its place.
    The addition reads as follows:


Sec.  112.5  Review and approval of labeling.

* * * * *
    (b) A data summary, available on the Internet at 
productdata.aphis.usda.gov, shall be used with each submission of 
efficacy and safety data in support of a label claim. Manufacturers 
will submit the efficacy and safety data information with either the 
efficacy and safety studies or at the time of label submission. This 
information will be posted at productdata.aphis.usda.gov to allow 
public disclosure of product performance.
* * * * *

    Done in Washington, DC, this 6th day of July 2015.
Kevin Shea,
Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 2015-16898 Filed 7-9-15; 8:45 am]
BILLING CODE 3410-34-P