[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]
========================================================================
Rules and Regulations
Federal Register
________________________________________________________________________
This section of the FEDERAL REGISTER contains regulatory documents
having general applicability and legal effect, most of which are keyed
to and codified in the Code of Federal Regulations, which is published
under 50 titles pursuant to 44 U.S.C. 1510.
The Code of Federal Regulations is sold by the Superintendent of Documents.
Prices of new books are listed in the first FEDERAL REGISTER issue of each
week.
========================================================================
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.
-----------------------------------------------------------------------
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 (http://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 http://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'' (http://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 ``(http://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