[Federal Register Volume 85, Number 146 (Wednesday, July 29, 2020)]
[Rules and Regulations]
[Pages 45505-45513]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-15441]
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Rules and Regulations
Federal Register
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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.
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Federal Register / Vol. 85, No. 146 / Wednesday, July 29, 2020 /
Rules and Regulations
[[Page 45505]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 514
[Docket No. FDA-2017-N-6381]
RIN 0910-AH51
Postmarketing Safety Reports for Approved New Animal Drugs;
Electronic Submission Requirements
AGENCY: Food and Drug Administration, Health and Human Services (HHS).
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
issuing a final rule to require electronic submission of certain
postmarketing safety reports for approved new animal drugs. The final
rule also provides a procedure for requesting a temporary waiver of the
electronic submission requirement.
DATES: This rule is effective August 28, 2020. For the applicable
compliance date, please see section V, ``Effective and Compliance
Dates'' in SUPPLEMENTARY INFORMATION.
ADDRESSES: For access to the docket to read background documents or
comments received, go to https://www.regulations.gov and insert the
docket number found in brackets in the heading of this final rule into
the ``Search'' box and follow the prompts, and/or go to the Dockets
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: With regard to the final rule: Linda
Walter-Grimm, Center for Veterinary Medicine (HFV-240), Food and Drug
Administration, 7519 Standish Pl., MPN4, Rm. 2666, Rockville, MD 20855,
240-402-5762, [email protected].
With regard to the information collection: Domini Bean, Office of
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-5733,
[email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose of the Final Rule
B. Summary of the Major Provisions of the Final Rule
C. Legal Authority
D. Costs and Benefits
II. Background
A. Need for the Regulation
B. Summary of Comments to the Proposed Rule
C. General Overview of the Final Rule
III. Legal Authority
IV. Comments on the Proposed Rule and FDA Response
A. Introduction
B. Description of General Comments and FDA Response
C. Specific Comments and FDA Response
V. Effective and Compliance Dates
VI. Economic Analysis of Impacts
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism
X. Consultation and Coordination With Indian Tribal Governments
XI. References
I. Executive Summary
A. Purpose of the Final Rule
The purpose of this rulemaking is to require electronic submission
of certain postmarketing safety reports for approved new animal drugs
and to provide a procedure for requesting a temporary waiver of the
requirement.
We require applicants to submit to us postmarketing safety reports
of adverse drug experiences and product/manufacturing defects for
approved new animal drugs (see Sec. 514.80 (21 CFR 514.80)). An
applicant is defined as a person or entity who owns or holds on behalf
of the owner the approval for a new animal drug application (NADA) or
an abbreviated new animal drug application (ANADA) and is responsible
for compliance with applicable provisions of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) and regulations (see Sec. 514.3 (21 CFR
514.3)). In addition, a nonapplicant, defined in Sec. 514.3 as any
person other than the applicant whose name appears on the label and who
is engaged in manufacturing, packing, distribution, or labeling of the
product, may elect to submit adverse drug experience reports directly
to us (Sec. 514.80(b)(3)).
The continuous monitoring of new animal drugs affords the primary
means by which we obtain information regarding problems with the safety
and efficacy of marketed approved new animal drugs, as well as product/
manufacturing problems. Postapproval marketing surveillance is
important to ensure the continued safety and effectiveness of new
animal drugs. Drug effects can change over time and other effects may
not manifest until years after the approval.
Finalizing this rule will improve our systems for collecting and
analyzing postmarketing safety reports. The change will help us to more
rapidly review postmarketing safety reports, identify emerging safety
problems, and disseminate safety information in support of our public
health mission. In addition, the amendments will facilitate
international harmonization and exchange of safety information. This
rule also provides a procedure for requesting a temporary waiver of the
electronic submission requirement.
B. Summary of the Major Provisions of the Final Rule
The rule amends the records and reports regulation in part 514 (21
CFR part 514) to include the following:
Procedures relating to the electronic submission of
certain postmarketing safety reports for approved new animal drugs; and
Procedures for requesting a temporary waiver of the
electronic submission requirement.
The final rule requires electronic submission for the following
reports for approved new animal drugs: (1) 3-day alert reports that
applicants elect to submit as a courtesy copy directly to FDA's Center
for Veterinary Medicine (CVM) in addition to the requirement they have
to submit these reports on paper Form FDA 1932 to the appropriate FDA
District Office or local FDA resident post; (2) 15-day alert reports
and followup reports; product/manufacturing defect and adverse drug
experience reports submitted by nonapplicants who elect to report
adverse drug experiences directly to CVM in addition to providing these
reports to the applicant; and (3) product/manufacturing defect and
adverse drug experience reports (including reports of previously not
reported adverse drug experiences that occur in postapproval studies)
required
[[Page 45506]]
to be submitted as part of the periodic drug experience report. We are
replacing the current paper submission process with the electronic
submission requirement and a procedure for requesting a temporary
waiver of the electronic submission requirement. Finally, the final
rule clarifies where to submit reports not required to be submitted
electronically. Under the final rule, we continue to require 3-day
alert reports to be submitted to the appropriate FDA District Office or
local FDA resident post on paper. However, as noted, if in addition to
the report an applicant submits on paper Form FDA 1932 to the
appropriate FDA District Office or local FDA resident post, an
applicant elects to submit a 3-day field alert report directly to CVM
as a ``courtesy copy,'' the applicant will be required to submit the
``courtesy copy'' of the report to CVM electronically.
C. Legal Authority
Our legal authority to require electronic submission of
postmarketing safety reports for approved new animal drugs derives from
sections 201, 301, 501, 502, 512, and 701 of the FD&C Act (21 U.S.C.
321, 331, 351, 352, 360b, and 371).
D. Costs and Benefits
The quantifiable benefit of this rule is annual cost savings of
$7,908 from reduced data entry time for CVM. The other benefits of this
final rule would be to animal health and are not quantifiable. The main
cost of this rule is a one-time upfront cost to industry of $73,500 for
changing standard operating procedures (SOPs) and training employees to
electronically submit postmarketing safety reports in accordance with
the new SOPs. Recurring costs to the Agency would be $161 per year, for
processing the waivers to the electronic reporting requirement.
Annualizing these costs over a 15-year time horizon (from 2018 to
2033), we estimate total annualized costs to be $6,139 at a 3 percent
discount rate, and total annualized costs of $7,703 at a 7 percent
discount rate. The annualized net benefit of this rule is -$880 at a 3
percent discount rate and -$2,444 at a 7 percent discount rate. The
present value of the net benefits is -$10,504 at a 3 percent discount
rate and -$22,262 at a 7 percent discount rate over a 15-year time
horizon.
II. Background
A. Need for the Regulation
When a new animal drug is approved and enters the market, the
product is introduced to a larger population in settings different from
the controlled studies required by the approval process. New
information generated during the postmarketing period offers further
insight into the benefits and/or risks of the product, and evaluation
of this information is important to ensure the safe and effective use
of these products.
CVM receives information regarding adverse drug experiences for
approved new animal drugs from postmarketing safety reports. For over
25 years, we have received these safety reports on paper. However, the
majority of submitters have chosen, voluntarily, to utilize electronic
submission as electronic means became available.
In the Federal Register of February 14, 2018 (83 FR 6480), we
proposed to amend our existing animal drug records and reports
regulation in part 514 to require electronic submission of certain
postmarketing safety reports for approved new animal drugs and provide
a procedure for requesting a temporary waiver of the requirement (83 FR
6480 at 6484). We set forth the rationale that electronic submission
improves our ability to process and archive postmarketing safety
reports in a timely manner, and to make postmarketing reports more
readily available for analysis (83 FR 6480 at 6482).
Electronic submission of postmarketing safety reports:
Expedites our access to safety information and provides us
data in a format that will support more efficient and comprehensive
reviews;
Enhances our ability to rapidly communicate information
about suspected problems to animal owners, veterinarians, consumers,
and industry within the United States and internationally in support of
our public health mission; and
Eliminates or reduces the time and costs to industry
associated with submitting paper reports, and the time, costs, errors,
and physical storage needs of the Agency associated with manually
entering data from paper reports into the electronic system for review
and analysis.
Electronic submission of postmarketing safety reports allows us to
be more responsive to rapidly occurring changes in the technological
environment. Consistent with our current practice for voluntarily
provided electronic submissions, the final rule requires that data in
electronic submissions conform to the data elements in Form FDA 1932
and our technical documents on how to provide electronic submissions
(e.g., method of transmission and processing, media, file formats,
preparation and organization of files). The final rule allows us to
issue updated technical documents, as necessary. The most current
information on submitting postmarketing safety reports to us in
electronic format can be found on our web page at https://www.fda.gov/animal-veterinary/report-problem/veterinary-adverse-event-reporting-manufacturers (see, e.g., ``Instructions for Electronic Submission of
Mandatory Adverse Event Reports to FDA CVM''). As necessary, we will
revise the technical specifications referenced in our technical
documents to address changing technical specifications or any
additional specifications needed for electronic submission. Using
guidance documents and technical documents to communicate these
technical specifications will permit us to be more responsive to
rapidly occurring changes in the technological environment.
The final rule is also an important step in our continuing efforts
to harmonize our postmarketing safety reporting regulations with
international standards for submitting safety information. Currently,
the technical specifications referenced in our guidance documents
supporting the voluntary electronic submission processes rely upon and
adopt certain safety reporting and transmission standards recommended
by the International Cooperation on Harmonisation of Technical
Requirements for Registration of Veterinary Medicinal Products (VICH).
VICH was formed to facilitate the harmonization of technical
requirements for the marketing authorization or ``registration'' of
veterinary medicinal products among three regions: the European Union,
Japan, and the United States. Our electronic submission specifications
allow applicants or nonapplicants to submit postmarketing safety
reports using the Health Level 7 (HL7) Individual Case Safety Report
(ICSR) standard that has been adopted worldwide by VICH. In this final
rule, we reaffirm our intention to continue to rely on these VICH-
recommended standards. We believe the continued use of VICH standards
will promote harmonization of safety reporting among regulatory
agencies and facilitate the international exchange of postmarketing
safety information. Accordingly, this final rule is consistent with our
ongoing initiatives to encourage the widest possible use of electronic
submission and to promote international harmonization of safety
reporting for animal drug products through reliance
[[Page 45507]]
on VICH standards. We anticipate that the final rule will enhance
industry's global pharmacovigilance practices by allowing it to use
common data elements and transmission standards when submitting ICSRs
to multiple regulators.
B. Summary of Comments to the Proposed Rule
We received two comment letters on the proposed rule by the close
of the comment period, each containing one or more comments on one or
more issues. We received comments from industry and an individual. Some
comments support our rulemaking and our ongoing efforts to improve our
systems for collecting and analyzing postmarketing safety reports. Some
comments offer suggestions for specific changes for us to consider
making to the subject regulations.
C. General Overview of the Final Rule
This final rule amends our animal drug records and reports
regulation at part 514 to require electronic submission of certain
postmarketing safety reports for approved new animal drugs. In
addition, the rule provides a procedure for requesting a temporary
waiver of the requirement. In this rulemaking, we finalize the
provisions in the proposed rule.
III. Legal Authority
Our legal authority for issuing this final rule is provided by
section 512(l) of the FD&C Act relating to records and reports
concerning approved new animal drugs and section 701(a) of the FD&C
Act. Section 512(l) of the FD&C Act requires that, following approval
of an NADA or ANADA, applicants must establish and maintain records and
make reports to the Agency of data related to experience, as prescribed
by regulation or order. FDA has general rulemaking authority under
section 701(a) of the FD&C Act, which permits the Secretary of Health
and Human Services to promulgate regulations for the efficient
enforcement of the FD&C Act. To implement section 512(l) of the FD&C
Act, FDA promulgated regulations for records and updates concerning
experience with new animal drugs (see Sec. 514.80). The final rule's
amendments to this regulation will further efficient enforcement of
section 512(l) by permitting records and reports to be reported
electronically.
IV. Comments on the Proposed Rule and FDA Response
A. Introduction
This section summarizes comments we received in response to the
proposed rule and our response to those comments. Both commenters
support our rulemaking and our ongoing efforts to improve our systems
for collecting and analyzing postmarketing safety reports. Some of the
comments offer suggestions for additional changes to the subject
regulations. We considered the comments we received in response to the
proposed rule in preparing this final rule. After considering these
comments, we are not making any changes to the codified language that
was included in the proposed rule.
In sections IV.B. through IV.C., we describe the comments received
on the proposed rule and provide our responses. To make it easier to
identify the comments and our responses, the word ``Comment,'' in
parentheses, appears before the comment's description, and the word
``Response,'' in parentheses, appears before our response. We have
numbered each comment to help distinguish between different comments.
We have grouped similar comments together under the same number, and,
in some cases, we have separated different issues discussed in the same
comment and designated them as distinct comments for purposes of our
responses. The number assigned to each comment or comment topic is
purely for organizational purposes and does not signify the comment's
value or importance or the order in which comments were received.
B. Description of General Comments and FDA Response
Two comments make general remarks supporting the proposed rule
without focusing on a particular proposed provision.
(Comment 1) Comments generally support our efforts to require
electronic submission of certain postmarketing safety reports for
approved new animal drugs. One comment recognizes that the requirement
of electronic submission would greatly benefit the Agency and animal
health by supporting quicker access to postmarketing safety
information. Another comment applauds our efforts to improve our
systems for collecting and analyzing postmarketing safety reports and
to facilitate international harmonization and exchange of safety
information.
(Response 1) We appreciate the general support that the comments
express. As noted in section II.A., we expect this rule to expedite our
access to safety information and provide us data in a format that will
support more efficient and comprehensive reviews. This will enhance our
ability to rapidly communicate information about suspected problems to
animal owners, veterinarians, consumers, and industry within the United
States and internationally in support of our public health mission.
C. Specific Comments and FDA Response
Several comments make specific remarks regarding particular
proposed provisions. In this section, we discuss and respond to such
comments.
(Comment 2) One comment states that, although in favor of
electronically reporting 3-day alerts to CVM in addition to reporting
to the appropriate FDA District Office or local resident post, until
such time that this can be accomplished via a single mechanism (i.e.,
electronic reporting to both segments of the Agency simultaneously),
this places an undue burden on industry both in time and resources as
this would require reporting electronically to CVM while continuing to
file paper Form FDA 1932 to District Offices or local resident posts.
(Response 2) We currently require 3-day alert reports to be
submitted to the appropriate FDA District Office or local FDA resident
post on paper (see Sec. 514.80(b)(1)). However, if in addition to that
report an applicant elects to submit a 3-day field alert report
directly to CVM (i.e., a ``courtesy copy''), we proposed to require the
applicant to submit that additional copy of the report to CVM
electronically (see proposed Sec. 514.80(b)(1)). At this time FDA
District Offices do not have the technology to receive Form FDA 1932
electronically, so we cannot mandate electronic reporting to FDA
District Offices at this time. In addition, the FDA District Offices
and local FDA resident posts use a different database for tracking such
reports, and do not have direct access to the CVM Adverse Drug Event
(ADE) database (which receives ADE information in part from Form FDA
1932). We agree that development of a single mechanism to report 3-day
alert reports via electronic Form FDA 1932 to both the FDA District
Office (or local FDA resident post) and CVM is ideal, and we are
interested in developing this capacity; however, this effort is
preliminary and investigatory at this time. As there is currently no
requirement to provide a ``courtesy copy'' of 3-day alert reports to
CVM, the required electronic submission of such copies would only
burden those applicants that choose to provide them despite any
additional time and resources needed to do so. Therefore, in this final
rule, we are keeping the language of the final rule as proposed at
[[Page 45508]]
Sec. 514.80(b)(1). CVM will continue to collaborate with the FDA
District Office or local resident post to followup as appropriate in
response to 3-day field alert reports submitted directly to the FDA
District Office or local resident post.
(Comment 3) One comment notes that, since the implementation of
electronic reporting capability, postmarketing safety reports may be
submitted to us via Extensible Markup Language (XML), which is designed
to store and transport data and be both human-readable and machine-
readable. Therefore, there is no official Form FDA 1932 version of
these reports to provide to an inspector during manufacturing site FDA
inspections. In addition, the comment continues, inspectors are not
well versed in reading the XML formats created from electronically
submitted reports. The comment suggests that we provide training to
inspectors to help them better understand how to read the XML format
for case data or that we provide industry with guidance for an
alternative form that could be generated from the database that
satisfies the inspectors' needs during site inspections.
(Response 3) We recognize the comment's concerns with regard to
utility of the XML format information during inspections. We appreciate
the commenter's interest in either preparing more easily readable
versions of electronically submitted reports for inspectors or
providing training to inspectors in reading the XML format of
electronically submitted reports. We intend to consider these
suggestions so that inspectors are better able to access the
information they need during an inspection. However, the comment did
not request any changes to the language in proposed Sec. 514.80(b)(1),
nor do we see a reason to make any changes based on the concerns and
suggestions included in the comment.
(Comment 4) One comment notes that, while the proposed rule
provides a procedure for requesting a temporary waiver of the
electronic submission requirement for ``good cause'' (i.e., crisis
situations that impact an applicant's or nonapplicant's ability to
report electronically, such as natural disasters, pandemics, and
terrorism), the proposed rule does not change the content, frequency,
or timeline for submission of the postmarketing safety reports to the
Agency. The comment suggests that, when the Agency's Electronic
Submission Gateway or Safety Reporting Portal is down, we should grant
a temporary waiver of the electronic submission requirement for the
amount of time the Agency website or portal is down.
(Response 4) We disagree that the Agency should automatically grant
a temporary waiver from the electronic submission requirement for the
amount of time that the Agency's Electronic Submission Gateway or
Safety Reporting Portal is down. As stated in the proposed rule,
electronic submission improves our ability to process and archive
postmarketing safety reports in a timely manner, and to make
postmarketing reports more readily available for analysis (83 FR 6480
at 6482). We also stated in the proposed rule that an applicant or
nonapplicant experiencing technical difficulty that temporarily
prevents use of the Electronic Submission Gateway could, as a backup,
electronically submit reports using the Safety Reporting Portal. An
applicant or nonapplicant that relies on the Safety Reporting Portal
but experiences a short-term, temporary interruption of internet
services could, as a backup, electronically submit reports from any
other computer with access to a working internet connection (83 FR 6480
at 6485). It is highly unlikely that both the Agency's Electronic
Submission Gateway or Safety Reporting Portal would be down at the same
time. In the unlikely event that the Agency experiences a prolonged
system outage or other major technical problem (which would include the
highly unlikely situation where both the Agency's Electronic Submission
Gateway or Safety Reporting Portal are down), the Agency does not
intend to enforce the requirement to submit reports electronically so
long as an applicant or nonapplicant submits reports in an alternate
format (most likely on paper using Form FDA 1932).
We are not waiving the required content, frequency, or timeline for
submission of the postmarketing safety reports to the Agency, and are
finalizing proposed Sec. 514.80(d) without change. The rule requires
applicants and nonapplicants to submit a waiver request to us in
writing. The initial request for a waiver may be by telephone or email
to CVM's Division of Veterinary Product Safety, with prompt written
followup submitted as a letter to the application(s). Applicants and
nonapplicants should be prepared to comply with an Agency request for
submission in an alternate format by maintaining the capability to
submit paper reports using Form FDA 1932, if needed.
In addition to the comments specific to this rulemaking that we
addressed previously in this preamble, we received general comments
expressing views about matters that are not related to this rulemaking.
Therefore, these general comments do not require a response.
V. Effective and Compliance Dates
This rule is effective August 28, 2020. Applicants and
nonapplicants must comply with the electronic submission requirement in
the final rule when submitting their reports beginning on July 29,
2021.
VI. Economic Analysis of Impacts
We have examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, Executive Order 13771, the
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and
13563 direct us to assess all costs and benefits of available
regulatory alternatives and, when regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). Executive Order 13771
requires that the costs associated with significant new regulations
``shall, to the extent permitted by law, be offset by the elimination
of existing costs associated with at least two prior regulations.''
This final rule is not an economically significant regulatory action as
defined by Executive Order 12866.
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because the costs of the rule are minimal in both absolute
value and in comparison to average yearly sales of small firms in this
industry, we certify that the final rule will not have a significant
economic impact on a substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before issuing ``any rule that includes
any Federal mandate that may result in the expenditure by State, local,
and tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation) in any one
year.'' The current threshold after adjustment for inflation is $156
million, using the most current (2019) Implicit Price Deflator for the
Gross Domestic Product. This final rule would not result in an
expenditure in any year that meets or exceeds this amount.
[[Page 45509]]
Currently, most submitters have chosen, voluntarily, to use
electronic submission for the reports that would be affected by this
final rule. As of 2016, 99.7 percent of postmarketing safety reports
eligible for electronic submission were electronically submitted. Thus,
this final rule would affect a small proportion of these reports.
The quantifiable benefit of this rule is annual cost savings of
$5,259 from reduced data entry time for CVM. The other benefits of this
final rule would be to animal health and are not quantifiable. The main
cost to this rule is a one-time upfront cost to industry of $73,500 for
changing SOPs and training employees to electronically submit
postmarketing safety reports in accordance with the new SOPs. Recurring
costs to the Agency would be $161 per year, for processing the waivers
to the electronic reporting requirement. Annualizing these costs over a
15-year time horizon (from 2018 to 2033), we estimate total annualized
costs to be $6,139 at a 3 percent discount rate, and total annualized
costs of $7,703 at a 7 percent discount rate. The annualized net
benefit of this rule is -$880 at a 3 percent discount rate and -$2,444
at a 7 percent discount rate. The present value of the net benefits is
-$10,504 at a 3 percent discount rate and -$22,262 at a 7 percent
discount rate over a 15-year time horizon.
Table 1--Summary of Benefits and Costs in 2017 Dollars Over a 15-Year Time Horizon
--------------------------------------------------------------------------------------------------------------------------------------------------------
Units
Primary Low High ------------------------------------
Category estimate estimate estimate Year Discount Period Notes
dollars rate (%) covered
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
Annualized................................ $5,259 .......... .......... 2017 7 15 ................................
Monetized $/year.......................... 5,259 .......... .......... 2017 3 15 ................................
Annualized................................ .......... .......... .......... .......... 7 .......... ................................
Quantified................................ .......... .......... .......... .......... 3 .......... ................................
Qualitative............................... .......... .......... .......... .......... .......... .......... ................................
Costs:
Annualized................................ 7,703 .......... .......... 2017 7 15 ................................
Monetized $/year.......................... 6,139 .......... .......... 2017 3 15 ................................
Annualized................................ .......... .......... .......... .......... 7 .......... ................................
Quantified................................ .......... .......... .......... .......... 3 .......... ................................
Qualitative............................... .......... .......... .......... .......... .......... .......... ................................
Transfers:
Federal................................... .......... .......... .......... .......... 7 .......... ................................
Annualized Monetized $/year............... .......... .......... .......... .......... 3 .......... ................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
From/To From:
To: ..........
--------------------------------------------------------------------------------------------------------------------------------------------------------
Other......................................... .......... .......... .......... .......... 7 .......... ................................
Annualized Monetized $/year................... .......... .......... .......... .......... 3 .......... ................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
From/To From:
To: ..........
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
3State, Local or Tribal Government:
3Small Business:
3Wages:
3Growth:
--------------------------------------------------------------------------------------------------------------------------------------------------------
In line with Executive Order 13771, in table 2 we estimate present
and annualized values of costs and cost savings over an infinite time
horizon. Based on these cost-savings this final rule would be
considered a deregulatory action under Executive Order 13771. Our
primary estimate for the present value of the net costs over an
infinite time horizon is -$3,837 (or a cost savings of $3,837) at a 7
percent discount rate and -$96,287 at a 3 percent discount rate in 2016
dollars.
Table 2--Executive Order 13771 Summary Table
[In 2016 dollars over an infinite time horizon]
----------------------------------------------------------------------------------------------------------------
Lower Upper Lower Upper
Primary bound bound Primary bound bound
(7%) (7%) (7%) (3%) (3%) (3%)
----------------------------------------------------------------------------------------------------------------
Present Value of Costs.................. $69,720 .......... .......... $75,346 .......... ..........
Present Value of Cost Savings........... 110,711 .......... .......... 258,326 .......... ..........
-----------------------------------------------------------------------
Present Value of Net Costs.......... (40,991) .......... .......... (182,980) .......... ..........
Annualized Costs........................ 4,880 .......... .......... 2,260 .......... ..........
Annualized Cost Savings................. 7,750 .......... .......... 7,750 .......... ..........
-----------------------------------------------------------------------
Annualized Net Costs................ (2,869) .......... .......... (5,489) .......... ..........
----------------------------------------------------------------------------------------------------------------
[[Page 45510]]
We have developed a comprehensive Economic Analysis of Impacts that
assesses the impacts of the final rule. The full analysis of economic
impacts is available in the docket for this final rule (Ref. 1) and at
https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.
VII. Analysis of Environmental Impact
We have determined under 21 CFR 25.30(h) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VIII. Paperwork Reduction Act of 1995
This final rule contains information collection provisions that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521). The
title, description, and respondent description of the information
collection provisions are shown in the following paragraphs with an
estimate of the one-time and recurring reporting and recordkeeping
burdens. Included in the estimate is the time for reviewing
instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing each
collection of information.
Title: Records and Reports Concerning Experience with Approved New
Animal Drugs--OMB Control Number 0910-0284--Revision.
Description: This final rule revises the existing information
collection requirements in the postmarketing safety reporting
regulations for approved new animal drugs to require electronic
submission of certain postmarketing safety reports for approved new
animal drugs. This rule does not change the content of these
postmarketing reports. It only requires that they be submitted in an
electronic form. The rule also provides a procedure for requesting a
temporary waiver of the requirement.
Description of Respondents: Respondents to the information
collection provisions of this rule are applicants and nonapplicants.
Reporting: Currently, the postmarketing safety reporting
regulations for approved new animal drugs include requirements to
submit to us postmarketing safety reports of adverse drug experiences
and product/manufacturing defects. Section 514.80 requires applicants
and nonapplicants to keep records of and report to us data, studies,
and other information concerning experience with new animal drugs for
each approved NADA and ANADA. Following complaints from animal owners
or veterinarians, or following their own detection of a problem,
applicants or nonapplicants are required to submit adverse event
reports and product/manufacturing defect reports under Sec.
514.80(b)(1) through (3) and (b)(4)(iv)(A) and (C) on Form FDA 1932.
Form FDA 1932 may be submitted on paper or electronically via the
Electronic Submission Gateway or Safety Reporting Portal. Form FDA
1932a (the voluntary reporting form) is used by veterinarians and the
public to submit adverse event reports, product defects, and lack of
effectiveness complaints directly to FDA. Form FDA 1932a may be
submitted on paper or may be submitted electronically by completing and
emailing a fillable PDF form. Form FDA 2301 is used to submit the
required transmittal of periodic reports (Sec. 514.80(b)(4)); special
drug experience reports (Sec. 514.80(b)(5)(i)); promotional material
for new animal drugs (Sec. 514.80(b)(5)(ii)); and distributor
statements (Sec. 514.80(b)(5)(iii)). Form FDA 2301 may be submitted on
paper, may be submitted electronically by completing and emailing a
fillable PDF form, or may be submitted electronically via CVM's
eSubmitter. We review the records and reports required in Sec. 514.80
and the voluntary reports to facilitate a determination under section
512(e) of the FD&C Act as to whether there may be grounds for
suspending or withdrawing approval of the new animal drug.
The final rule revises these requirements to require electronic
submission of the following postmarketing safety reports for approved
new animal drugs:
Three-day alert reports that applicants elect to submit
directly to CVM as a ``courtesy copy'' in addition to the requirement
that they have to submit these reports on paper Form FDA 1932 to the
appropriate FDA District Office or local FDA resident post (Sec.
514.80(b)(1);
Fifteen-day alert reports (Sec. 514.80(b)(2)(i)) and
followup reports (Sec. 514.80(b)(2)(ii));
Product/manufacturing defects and adverse drug experience
reports submitted by nonapplicants who elect to report adverse drug
experiences directly to FDA under Sec. 514.80(b)(3) in addition to
providing these reports to the applicant; and
Product/manufacturing defects and adverse drug experience
reports (including reports of previously not reported adverse drug
experiences that occur in postapproval studies) required to be
submitted as part of the periodic drug experience report (Sec.
514.80(b)(4)(iv)(A) and (C)).
We currently require 3-day alert reports to be submitted to the
appropriate FDA District Office or local FDA resident post on paper
(see Sec. 514.80(b)(1)). As noted previously, the regulation does not
require electronic submission of 3-day field alert reports (Sec.
514.80(b)(1)). These reports will continue to be submitted on paper
Form FDA 1932 directly to the appropriate FDA District Office or local
resident post. However, as noted, if an applicant elects to submit a 3-
day field alert report directly to CVM as a ``courtesy copy,'' the
applicant will be required to submit the report electronically. This
will not alleviate the applicant's responsibility to submit this report
to the FDA District Field Office or local FDA resident post on paper
Form FDA 1932.
The final rule also revises these requirements to allow applicants
or nonapplicants to request a temporary waiver from the electronic
submission requirement for ``good cause'' shown. We anticipate that
temporary waivers will only be needed in rare circumstances that impact
an applicant's or nonapplicant's ability to report electronically, such
as natural disasters, pandemics, and terrorism.
In the February 14, 2018, proposed rule, we included an analysis of
the information collection provisions of the proposal under the PRA and
requested comments on four topics relevant to that analysis (83 FR 6480
at 6487 through 6488). We have summarized and responded to these
comments in sections IV.B. through IV.C., but have made no changes to
the burden estimate in our proposed rule.
We estimate the reporting burden of this collection of information
as follows:
[[Page 45511]]
Table 3--Estimated Recurring Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Average
21 CFR section Form FDA No. Number of responses per Total annual burden per Total hours
respondents respondent responses response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Electronic submission of postmarketing safety reports 1932 15 18 270 1 270
under Sec. 514.80(b)(1), (b)(2)(i) and (ii), (b)(3),
and (b)(4)(iv)(A) and (C)..............................
Request for waiver, Sec. 514.80(d)(2)................. N/A 1 1 1 1 1
-----------------------------------------------------------------------------------------------
Total............................................... .............. .............. .............. 271 .............. 271
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 3 shows the estimated recurring reporting burden associated
with the final rule. In section II.F. of the Final Regulatory Impact
Analysis (FRIA), we estimated that 15 firms submitted a paper Form FDA
1932 report from 2011 to 2015 and thus will be affected by the rule's
requirement to submit electronically. As stated in the FRIA, we
estimate that in 2016 CVM received 270 of the affected postmarketing
safety reports on paper. We calculate the number of responses per
respondent as the total annual responses divided by the number of
respondents. We estimate that, on average, it will take 1 hour to
submit electronic postmarketing safety reports for approved new animal
drugs, for a total of 270 hours. We base our estimate of 1 hour per
report on our experience with electronic postmarketing safety
reporting. In the FRIA, we also estimated the burdens associated with
submission of waiver requests. We expect very few waiver requests (see
section II.F.2. of the FRIA), estimating that one firm will request a
waiver annually under Sec. 514.80(d)(2). We assume a waiver request
takes 1 hour to prepare and submit to us. Together, this results in a
total of 271 hours and 271 responses. We are also adding 1 hour to the
paper reporting collection to reflect the new waiver request process
under Sec. 514.80(d)(2).
We estimate the recordkeeping burden of this collection of
information as follows:
Table 4--Estimated One-Time Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
Activity Number of records per Total annual burden per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
Write New SOPs.................. 15 1 15 20 300
Training........................ 15 1 15 20 300
-------------------------------------------------------------------------------
Total....................... .............. .............. 30 .............. 600
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 4 shows the estimated one-time recordkeeping burden
associated with the final rule. This burden includes both the one-time
burden of creating new SOPs to submit the reports electronically and
the one-time cost of training employees to electronically submit
postmarketing safety reports to CVM in accordance with the new SOPs. In
section II.F. of the FRIA, we estimated that approximately 15 firms
will be affected by this rule. We assume it will take an average of 20
hours per firm to create new SOPs for electronic submission of
postmarketing safety reports and approximately 20 hours per firm to
complete the training of employees to electronically submit
postmarketing safety reports in accordance with the new SOPs. Together,
this results in a total of 600 hours and 30 records. We assume that
there are no capital costs associated with firms implementing this rule
(i.e., applicants and nonapplicants in the pharmaceutical industry
already have the computer and internet capacity necessary to
electronically submit postmarketing safety reports).
The information collection provisions in this final rule have been
submitted to OMB for review as required by section 3507(d) of the
Paperwork Reduction Act of 1995. Before the effective date of this
final rule, FDA will publish a notice in the Federal Register
announcing OMB's decision to approve, modify, or disapprove the
information collection provisions in this final rule. An Agency may not
conduct or sponsor, and a person is not required to respond to, a
collection of information unless it displays a currently valid OMB
control number.
IX. Federalism
We have analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
does not contain policies that have substantial direct effects on the
States, on the relationship between the National Government and the
States, or on the distribution of power and responsibilities among the
various levels of government. Accordingly, we conclude that the rule
does not contain policies that have federalism implications as defined
in the Executive order and, consequently, a federalism summary impact
statement is not required.
X. Consultation and Coordination With Indian Tribal Governments
We have analyzed this rule in accordance with the principles set
forth in Executive Order 13175. We have determined that the rule does
not contain policies that have substantial direct effects on one or
more Indian Tribes, on the relationship between the Federal Government
and Indian Tribes, or on the distribution of power and responsibilities
between the Federal Government and Indian Tribes. Accordingly, we
conclude that the rule does not contain policies that have tribal
implications as defined in the Executive order and, consequently, a
[[Page 45512]]
tribal summary impact statement is not required.
XI. References
1. Economic Analysis of Impacts; also available at: https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.
List of Subjects in 21 CFR Part 514
Administrative practice and procedure, Animal drugs, Confidential
business information, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
514 is amended as follows:
PART 514--NEW ANIMAL DRUG APPLICATIONS
0
1. The authority citation for part 514 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 354, 356a, 360b,
360ccc, 371, 379e, 381.
0
2. Section 514.80 is amended as follows:
0
a. Revise the entries in the table for paragraphs (b)(4), (d), (e), and
(g);
0
b. Add a fifth sentence to paragraph (b)(1); and
0
c. Revise the last sentence of paragraph (b)(2)(i); the third sentence
of paragraph (b)(2)(ii); the last sentence of paragraph (b)(3);
paragraphs (b)(4)(iv)(A) and (C); the fifth sentence of paragraph
(b)(4)(v); and paragraphs (d) and (g).
The addition and revisions read as follows:
Sec. 514.80 Records and reports concerning experience with approved
new animal drugs.
* * * * *
------------------------------------------------------------------------
21 CFR paragraph and
Purpose title
------------------------------------------------------------------------
* * * * * * *
What are the general requirements for 514.80(b)(4) Periodic
submission of periodic drug experience drug experience report.
reports, e.g., method of submission,
submission date and frequency, when is it to
be submitted, how many copies?.
How do I petition to change the date of
submission or frequency of submissions?
* * * * * * *
What reports must be submitted to FDA 514.80(d) Format for
electronically?. Submissions.
How can I apply for a waiver from the
electronic reporting requirements?
How do I obtain Form FDA 1932 and Form FDA
2301?
How long must I maintain records and reports 514.80(e) Records to be
required by this section?. maintained.
* * * * * * *
Where do I mail reports that are not required 514.80(g) Mailing
to be submitted electronically?. addresses.
* * * * * * *
------------------------------------------------------------------------
* * * * *
(b) * * *
(1) * * * If the applicant elects to also report directly to the
FDA's Center for Veterinary Medicine (CVM), the applicant must submit
the report to CVM in electronic format as described in paragraph (d)(1)
of this section, unless the applicant obtains a waiver under paragraph
(d)(2) of this section or FDA requests the report in an alternate
format.
(2) * * *
(i) * * * The report must be submitted to FDA in electronic format
as described in paragraph (d)(1) of this section, unless the applicant
obtains a waiver under paragraph (d)(2) of this section or FDA requests
the report in an alternate format.
(ii) * * * A followup report must be submitted to FDA in electronic
format as described in paragraph (d)(1) of this section, unless the
applicant obtains a waiver under paragraph (d)(2) of this section or
FDA requests the report in an alternate format. * * *
(3) * * * If the nonapplicant elects to also report directly to
FDA, the nonapplicant must submit the report to FDA in electronic
format as described in paragraph (d)(1) of this section, unless the
nonapplicant obtains a waiver under paragraph (d)(2) of this section or
FDA requests the report in an alternate format.
(4) * * *
(iv) * * *
(A) Product/manufacturing defects and adverse drug experiences not
previously reported under paragraphs (b)(1) and (2) of this section
must be reported individually to FDA in electronic format as described
in paragraph (d)(1) of this section, unless the applicant obtains a
waiver under paragraph (d)(2) of this section or FDA requests the
report in an alternate format.
* * * * *
(C) Reports of previously not reported adverse drug experiences
that occur in postapproval studies must be reported individually to FDA
in electronic format as described in paragraph (d)(1) of this section,
unless the applicant obtains a waiver under paragraph (d)(2) of this
section or FDA requests the report in an alternate format.
(v) * * * The summaries must state the time period on which the
increased frequency is based, time period comparisons in determining
increased frequency, references to any reports previously submitted
under paragraphs (b)(1), (2), and (3) and (b)(4)(iv)(A) and (C) of this
section, the method of analysis, and the interpretation of the results.
* * *
* * * * *
(d) Format for submissions--(1) Electronic submissions. Except as
provided in paragraph (d)(2) of this section, reports submitted to FDA
under paragraphs (b)(2)(i) and (ii), (b)(3), and (b)(4)(iv)(A) and (C)
of this section and reports submitted to CVM under paragraph (b)(1) of
this section must be submitted in an electronic format that FDA can
process, review, and archive. Data provided in electronic submissions
must be in conformance with the data elements in Form FDA 1932 and FDA
technical documents describing transmission. As necessary, FDA will
issue updated technical documents on how to provide the electronic
submission (e.g., method of transmission and processing, media, file
formats, preparation, and organization of files). Unless requested by
FDA, paper copies of reports submitted electronically should not be
submitted to FDA.
(2) Waivers. An applicant or nonapplicant may request, in writing,
a temporary waiver of the electronic
[[Page 45513]]
submission requirements in paragraph (d)(1) of this section. The
initial request may be by telephone or email to CVM's Division of
Veterinary Product Safety, with prompt written followup submitted as a
letter to the application(s). FDA will grant waivers on a limited basis
for good cause shown. If FDA grants a waiver, the applicant or
nonapplicant must comply with the conditions for reporting specified by
FDA upon granting the waiver.
(3) Paper forms. If approved by FDA before use, a computer-
generated equivalent of Form FDA 1932 may be used for reports submitted
to the appropriate FDA District Office or local FDA resident post under
paragraph (b)(1) of this section and to FDA under paragraph (d)(2) of
this section, and a computer-generated equivalent of Form FDA 2301 may
be used for reports submitted to FDA under paragraph (b)(4) of this
section. Form FDA 1932 may be obtained on the FDA website, by
telephoning CVM's Division of Veterinary Product Safety, or by
submitting a written request to the following address: Food and Drug
Administration, Center for Veterinary Medicine, Division of Veterinary
Product Safety (HFV-240), 7500 Standish Pl., Rockville, MD 20855-2764.
Form FDA 2301 may be obtained on the FDA website, by telephoning CVM's
Division of Surveillance (HFV-210), or by submitting a written request
to the following address: Food and Drug Administration, Center for
Veterinary Medicine, Division of Surveillance (HFV-210), 7500 Standish
Pl., Rockville, MD 20855-2764.
* * * * *
(g) Mailing addresses. Three-day alert reports must be submitted to
the appropriate FDA District Office or local FDA resident post.
Addresses for District Offices and resident posts may be obtained on
the FDA website. Other reports not required to be submitted to FDA in
electronic format must be submitted to the following address: Food and
Drug Administration, Center for Veterinary Medicine, Document Control
Unit (HFV-199), 7500 Standish Pl., Rockville, MD 20855-2764.
* * * * *
Dated: July 2, 2020.
Stephen M. Hahn,
Commissioner of Food and Drugs.
[FR Doc. 2020-15441 Filed 7-28-20; 8:45 am]
BILLING CODE 4164-01-P