[Federal Register Volume 84, Number 63 (Tuesday, April 2, 2019)]
[Rules and Regulations]
[Pages 12505-12508]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-06187]
[[Page 12505]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 600
[Docket No. FDA-2017-N-7007]
RIN 0910-AH49
Removal of Certain Time of Inspection and Duties of Inspector
Regulations for Biological Products
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
issuing a final rule amending the general biologics regulations
relating to time of inspection requirements and also removing duties of
inspector requirements. FDA is taking this action to remove outdated
requirements and accommodate new approaches, such as a risk-based
inspection frequency for drug and device establishments, thereby
providing flexibility without diminishing public health protections.
This action is part of FDA's implementation of Executive Orders (E.O.s)
13771 and 13777. Under these E.O.s, FDA is comprehensively reviewing
existing regulations to identify opportunities for repeal, replacement,
or modification that will result in meaningful burden reduction, while
allowing the Agency to achieve our public health mission and fulfill
statutory obligations.
DATES: This rule is effective May 2, 2019.
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: Jenifer Stach, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.
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 This 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 Comments Regarding Proposed Revisions to
Sec. Sec. 600.21 and 600.22
C. Description of Comments Outside the Scope of This Rulemaking
V. Economic Analysis of Impacts
VI. Analysis of Environmental Impact
VII. Paperwork Reduction Act of 1995
VIII. Federalism
IX. Consultation and Coordination With Indian Tribal Governments
I. Executive Summary
A. Purpose of the Final Rule
FDA is issuing this final rule to amend the general biologics
regulations relating to time of inspection requirements and to remove
duties of inspector requirements. FDA is taking this action to remove
outdated requirements and accommodate new approaches, such as a risk-
based inspection frequency for drug and device establishments, thereby
providing flexibility without diminishing public health protections.
B. Summary of the Major Provisions of the Final Rule
This final rule revises the time of inspection requirements
contained in Sec. [thinsp]600.21 (21 CFR 600.21) and also removes the
duties of inspector requirements contained in Sec. [thinsp]600.22 (21
CFR 600.22). These changes to the biological product regulations
eliminate outdated requirements and accommodate new approaches, such as
a risk-based inspection frequency for drug and device establishments,
thereby providing flexibility without diminishing public health
protections. Revision and removal of these regulations does not change
the biological product establishment inspection requirements and duties
of an investigator requirements that apply under sections 704 and
510(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 374 and 360(h)) and section 351(c) of the Public Health Service
Act (PHS Act) (42 U.S.C. 262(c)).
C. Legal Authority
FDA is taking this action under the biological product provisions
of the PHS Act, and the drugs and general administrative provisions of
the FD&C Act, including sections 704 and 510(h) of the FD&C Act and
section 351(c) of the PHS Act.
D. Costs and Benefits
Because this final rule does not impose any additional regulatory
burdens, this regulation is not anticipated to result in any compliance
costs and the economic impact is expected to be minimal.
II. Background
A. Need for This Rulemaking
In the Federal Register on January 26, 2018, FDA published a
proposed rule entitled ``Removal of Certain Time of Inspection and
Duties of Inspector Regulations for Biological Products; Companion to
Direct Final Rule'' (83 FR 3631), as well as a companion direct final
rule entitled ``Removal of Certain Time of Inspection and Duties of
Inspector Regulations for Biological Products'' (83 FR 3586). To allow
for consideration of the issues raised in the comments to the proposed
rule, FDA withdrew the direct final rule in the Federal Register of May
7, 2018 (83 FR 19936). After careful consideration of these issues, FDA
is issuing this final rule to revise the time of inspection
requirements contained in Sec. [thinsp]600.21 and to remove the duties
of inspector requirements contained in Sec. [thinsp]600.22. As
discussed in the proposed rule, on February 24, 2017, President Donald
Trump issued E.O. 13777, ``Enforcing the Regulatory Reform Agenda'' (82
FR 12285, March 1, 2017). One of the provisions in the E.O. requires
Agencies to evaluate existing regulations and make recommendations to
the Agency head regarding their repeal, replacement, or modification,
consistent with applicable law. As one step in implementing the E.O.,
FDA published a notice in the Federal Register of September 8, 2017 (82
FR 42492) entitled ``Review of Existing Center for Biologics Evaluation
and Research Regulatory and Information Collection Requirements.'' In
that notice, FDA announced that it was conducting a review of existing
regulations to determine, in part, whether they can be made more
effective in light of current public health needs and to take advantage
of, and support, advances in innovation that have occurred since those
regulations took effect. As part of this initiative, FDA is updating
outdated regulations as specified in this rule.
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FDA's general biological products regulations in part 600 (21 CFR
part 600) are intended to help ensure the safety, purity, and potency
of biological products administered to humans. The revision and removal
of certain general biological products regulations are designed to
eliminate outdated requirements and accommodate new approaches, such as
a risk-based inspection frequency for drug and device establishments,
and provide flexibility without diminishing public health protections.
Specifically, this final rule revises Sec. [thinsp]600.21 and removes
Sec. 600.22.
B. Summary of Comments to the Proposed Rule
We received five comments on the proposed rule from individual
submitters. We received comments both in support of the proposed rule
and comments raising concerns over the proposed revisions to Sec. Sec.
[thinsp]600.21 and 600.22. These comments are further summarized in
section IV.
C. General Overview of the Final Rule
As discussed in the proposed rule (83 FR 3631 at 3633), FDA's
authority to conduct establishment inspections is included in both the
FD&C Act and the PHS Act. Specifically, section 704 of the FD&C Act and
section 351(c) of the PHS Act authorize the Agency to inspect
establishments that manufacture biological products. Following
enactment of the Food and Drug Administration Safety and Innovation Act
(FDASIA) (Pub. L. 112-144) on July 9, 2012, and as provided under the
provisions in E.O. 13777, FDA is revising Sec. [thinsp]600.21 and
removing Sec. [thinsp]600.22.
FDA is revising Sec. [thinsp]600.21 to remove the biennial
inspection requirement for biological product establishments that are
registered as drug establishments and for those that are registered as
device establishments. Before FDASIA was signed into law, section
510(h) of the FD&C Act provided, among other things, that drug and
device establishments registered with FDA must be inspected on a
biennial basis. Section 510(h) of the FD&C Act applies to biological
product establishments because all biological products are subject to
regulation under the drug or device provisions of the FD&C Act (in
addition to the biological product provisions of the PHS Act). Since
1983, FDA's biological product regulation at Sec. 600.21 has also
included a biennial inspection requirement, which was consistent with
the pre-FDASIA biennial inspection requirement in section 510(h) of the
FD&C Act.
With the enactment of FDASIA, however, the biennial inspection
requirement for drug establishments in section 510(h) of the FD&C Act
was replaced with a requirement that FDA inspect drug establishments in
accordance with a risk-based schedule established by FDA. Additionally,
the FDA Reauthorization Act of 2017 (FDARA) was signed into law on
August 18, 2017, and substantively amended the FD&C Act to, among other
things, revise section 510(h)(2) such that the biennial inspection
schedule for device establishments was also replaced by a risk-based
schedule. FDA has determined that the biennial inspection requirement
in Sec. 600.21 regarding the frequency of inspections is outdated and
no longer consistent with the FD&C Act (e.g., the risk-based inspection
schedule for drug and device establishments may result in scheduling
inspections at intervals of greater or less than 2 years for certain
biological product establishments).
FDA is also removing provisions in Sec. [thinsp]600.21 concerning
inspectional notice and the timing of pre-licensure reinspections of
biological product establishments, as these provisions are outdated and
unnecessary. As discussed in the proposed rule (83 FR 3631 at 3634),
inspectional notice is addressed in the Agency's practices for
inspections in its Standard Operating Procedures and Policies and in
the Investigations Operations Manual (IOM). With respect to the timing
of a reinspection of a biological product establishment following the
denial of a biologics license application, the general biologics
licensing provision at 21 CFR 601.4, which was issued subsequent to
Sec. 600.21, sets forth the administrative procedures following the
denial of a license; accordingly, the specific provision in Sec.
600.21 regarding timing of a reinspection following denial of a license
is unnecessary.
FDA has further decided that current Sec. [thinsp]600.22, which
requires specific duties of an FDA inspector, is unnecessary because
the requirements in Sec. [thinsp]600.22(a) through (h) are duplicative
of statutory requirements that apply to biological product inspections
under section 704 of the FD&C Act. Specifically, the inspection
requirements in section 704 of the FD&C Act encompass all of the
requirements outlined in Sec. [thinsp]600.22. Thus, we are removing
Sec. [thinsp]600.22(a) through (h).
The removal of these regulations, however, does not change the
establishment inspection requirements and duties of investigator
requirements specified in sections 704 and 510(h) of the FD&C Act,
section 351(c) of the PHS Act, or the procedures described in the IOM.
Additionally, it does not change the established process for risk-based
inspection planning and work planning.
III. Legal Authority
FDA is issuing this rule under the biological products provisions
of the PHS Act (42 U.S.C. 216, 262, 263, 263a, and 264) and the drugs
and general administrative provisions of the FD&C Act (21 U.S.C. 321,
351, 352, 353, 355, 356c, 356e, 360, 360i, 371, 374, and 379k-l). Under
these provisions of the PHS Act and the FD&C Act, we have the authority
to issue and enforce regulations designed to ensure that biological
products are safe, pure, and potent, and to prevent the introduction,
transmission, and spread of communicable disease.
IV. Comments on the Proposed Rule and FDA Response
A. Introduction
We received five comments on the proposed rule from individual
submitters. We describe and respond to the comments in sections IV. B
through IV. C. 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 Comments Regarding Revisions to Sec. Sec.
[thinsp]600.21 and 600.22
(Comment 1) One comment supported the proposed rule.
(Response 1) We acknowledge and appreciate the supportive comment.
(Comment 2) One comment expressed concern that the risk-based
inspection frequency will not be without negative health consequences.
The comment also stated that ``[R]isk Management is an identified known
weak element to a majority of biological and medical device companies''
and that the management and mitigation of risk without FDA oversight
for a number of years is going to be a high-risk endeavor.
(Response 2) We disagree that the risk-based inspection frequency
will have negative health consequences. The purpose of this rule is to
remove outdated requirements and accommodate new approaches, such as a
risk-based inspection frequency for
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device and drug establishments. We believe this final rule will provide
flexibility without diminishing public health protections. Furthermore,
as discussed in the preamble to the proposed rule (83 FR 3633),
establishing a risk-based schedule for inspections of drug
establishments registered with FDA was mandated with the enactment of
the FDASIA that was signed into law on July 9, 2012. In August 2017,
FDARA mandated a risk-based schedule for inspections of device
establishments registered with FDA. As a result of these amendments to
the FD&C Act, sections 510(h)(2) and (3) of the FD&C Act now include
requirements to establish a risk-based schedule for the inspection of
drug and device establishments. In accordance with section 510(h)(4) of
the FD&C Act, the risk-based schedule must consider, among other
things, the known safety risks of such establishments, including the
compliance history of the establishment; the record, history, and
nature of recalls linked to the establishment; the inherent risk of the
drug or device manufactured, prepared, propagated, compounded, or
processed at the establishment; the inspection frequency and history of
the establishment; and any other criteria deemed necessary and
appropriate by FDA. While we agree that application of the risk-based
inspection frequency may result in some establishments being inspected
less frequently than every 2 years, these establishments will have been
determined to be at a lower risk based on the Agency's evaluation of
the above factors. In addition, the resources saved by performing less
frequent inspections at lower risk establishments will allow FDA to
inspect those establishments deemed higher risk more frequently if
needed. Therefore, we believe the comment's concerns about negative
health consequences are addressed during FDA's review of the known
safety risks of drug and device establishments. The known safety risks
that FDA must consider in establishing a risk-based schedule are
outlined in section 510(h)(4) of the FD&C Act. With regard to ``[R]isk
Management,'' we note that any such discussion is outside the scope of
this rule.
(Comment 3) One comment expressed concern with FDA's implementation
and process for the review of existing regulations under E.O. 13771.
(Response 3) We reiterate that the purpose of this rule is to
remove outdated requirements and accommodate new approaches, such as
the risk-based inspection frequency for drug and device establishments
required by the FD&C Act, and to provide flexibility without
diminishing public health protections. With regard to FDA's
implementation and process for the review of existing regulations under
E.O. 13771, we note that any such discussion is outside the scope of
this rule.
(Comment 4) One comment expressed concern with respect to
determining the frequency of inspections and asserted that any revised
risk-based inspection schedule should provide for ``both more relaxed
and more frequent forms of inspection, if indicated by the conditions
and risks that are assessed.'' The comment also asserted that FDA must
``recognize that for products or processes for which quality is
important and significant failures of quality are unacceptable, there
may be a need for inspection more frequently than every two years, and
with the degree of inspection and discussion now contained in the
inspector duties under 600.20.''
(Response 4) As discussed in the preamble to the proposed rule (83
FR 3633), the risk-based inspection schedule for drug and device
establishments may result in scheduling inspections at intervals of
greater than 2 years for certain biological product establishments.
However, those establishments will have been determined to be at a
lower risk based on evaluation of the factors included in section
510(h)(4) of the FD&C Act. In addition, the resources saved by
performing less frequent inspections at lower risk establishments will
allow FDA to inspect those establishments deemed higher risk more
frequently when needed. We reiterate that the removal of these
regulations will not change the establishment inspection requirements
and duties of an investigator requirements specified in sections 704
and 510(h) of the FD&C Act and section 351(c) of the PHS Act.
Additionally, it will not change the established process for risk-based
inspection planning and work planning. Furthermore, this revision will
not change FDA's authority to inspect an establishment for special
cause, such as when FDA becomes aware of consumer complaints or adverse
event reports, signaling a possible product quality issue for which a
prompt inspection may be useful in investigating the matter. Therefore,
while we agree, in part, with the comment, we believe the concerns
expressed in the comment are addressed through FDA's review of the
known safety risks of drug and device establishments and by FDA's
ability to inspect as needed in the interest of patient safety. The
known safety risks that FDA must consider in establishing a risk-based
schedule are outlined in section 510(h)(4) of the FD&C Act.
C. Description of Comments Outside the Scope of This Rulemaking
(Comment 5) One comment requested an exemption to newly created
Occupational Safety and Health Administration (OSHA) requirements.
(Response 5) We decline to respond because the request is outside
the scope of this rule.
V. Economic Analysis of Impacts
We have examined the impacts of the final rule under E.O. 12866,
E.O. 13563, E.O. 13771, the Regulatory Flexibility Act (5 U.S.C. 601-
612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4).
E.O. 12866 and E.O. 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). E.O. 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.'' We believe that this
final rule is not a significant regulatory action as defined by E.O.
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 final rule does not impose any additional
regulatory burdens, we certify that this 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 $150
million, using the most current (2017) 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.
This rule is being issued to amend the general biologics
regulations by removing certain time of inspection requirements and the
duties of inspector requirements. This action is being taken
[[Page 12508]]
to remove outdated requirements, accommodate new approaches, and
provide flexibility without diminishing public health protections.
Because this rulemaking would remove regulations to be consistent with
updated practice and does not impose any additional regulatory burdens,
this rulemaking is not anticipated to result in any compliance costs
and the economic impact is expected to be minimal.
VI. Analysis of Environmental Impact
We have determined under 21 CFR 25.31(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.
VII. Paperwork Reduction Act of 1995
This final rule contains no collection of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.
VIII. Federalism
We have analyzed this final rule in accordance with the principles
set forth in E.O. 13132. We have 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.
IX. Consultation and Coordination With Indian Tribal Governments
We have analyzed this rule in accordance with the principles set
forth in E.O. 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 tribal summary
impact statement is not required.
List of Subjects in 21 CFR Part 600
Biologics, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR part 600 is amended as follows:
PART 600--BIOLOGICAL PRODUCTS: GENERAL
0
1. The authority citation for part 600 is revised to read as follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 356c, 356e, 360,
360i, 371, 374, 379k-l; 42 U.S.C. 216, 262, 263, 263a, 264.
Sec. [thinsp]600.21 [Amended]
0
2. Amend Sec. [thinsp]600.21 by removing the last three sentences.
Sec. [thinsp]600.22 [Removed and Reserved]
0
3. Remove and reserve Sec. [thinsp]600.22.
Dated: March 25, 2019.
Scott Gottlieb,
Commissioner of Food and Drugs.
[FR Doc. 2019-06187 Filed 4-1-19; 8:45 am]
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