[Federal Register Volume 85, Number 163 (Friday, August 21, 2020)]
[Rules and Regulations]
[Pages 51635-51639]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-17085]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 610
[Docket No. FDA-2018-N-4757]
RIN 0910-AH95
Revocation of the Test for Mycoplasma
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 to remove the specified test for the presence of
Mycoplasma for live virus vaccines and inactivated virus vaccines
produced from in vitro living cell cultures. The rule is being
finalized because the existing test for Mycoplasma is overly
restrictive in that it identifies only one test method in detail to be
used even though other methods also may be appropriate. More sensitive
and specific methods exist and are currently being practiced, and
removal of the specific method to test for Mycoplasma provides
flexibility for accommodating new and evolving technology and
capabilities without diminishing public health protections. This action
is part of FDA's implementation of Executive Orders under which 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 September 21, 2020.
[[Page 51636]]
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: Tami Belouin, 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. Introduction
B. Need for the Regulation
C. Summary of Comments to the Proposed Rule
III. Legal Authority
IV. Comments on the Proposed Rule and FDA Response
A. Introduction
B. Comments and FDA Response
V. Effective Date
VI. Economic Analysis of Impacts
A. Introduction
B. Summary of Costs and Benefits
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
FDA is removing the regulation requiring a specified test for the
presence of Mycoplasma for live virus vaccines produced from in vitro
living cell cultures and inactivated virus vaccines produced from such
living cell cultures because the regulation is overly restrictive in
that it identifies only one test method in detail to be used even
though other methods also may be appropriate. More sensitive and
specific methods exist and are currently being practiced, and removal
of the required test for Mycoplasma provides flexibility for
accommodating new and evolving technology and capabilities without
diminishing public health protections.
B. Summary of the Major Provisions of the Final Rule
The final rule removes Sec. 610.30 (21 CFR 610.30), which details
the method for Mycoplasma testing of samples of the virus harvest pool
and control fluid pool of live virus vaccines and inactivated virus
vaccines produced from in vitro living cell cultures.
C. Legal Authority
FDA is taking this action under the biological products provisions
of the Public Health Service Act (the PHS Act), and the drugs and
general administrative provisions of the Federal Food, Drug, and
Cosmetic Act (FD&C Act).
D. Costs and Benefits
Because this final rule will 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. Introduction
On February 24, 2017, Executive Order 13777, ``Enforcing the
Regulatory Reform Agenda'' (https://www.federalregister.gov/documents/2017/03/01/2017-04107/enforcing-the-regulatory-reform-agenda; 82 FR
12285, March 1, 2017) was issued. One of the provisions in the
Executive Order requires Agencies to evaluate existing regulations and
make recommendations to the Agency head regarding their repeal,
replacement, or modification, consistent with applicable law. As part
of this initiative, FDA is revoking a regulation as specified in this
final rule.
B. Need for the Regulation
It has become increasingly clear that the requirement specifying a
test for Mycoplasma is too restrictive for live virus vaccines and
inactivated virus vaccines produced from in vitro living cell cultures
because they specify particular methodologies when alternatives may be
available that provide the same or greater level of assurance of
safety. Modifications to Mycoplasma testing described in Sec. 610.30
must meet the requirements of 21 CFR 610.9.
Thus, the Agency believes that the regulation may no longer reflect
the current testing procedures as a general matter and that it is more
appropriate, flexible, and efficient to identify appropriate testing
requirements for particular products in the biologics license
application (BLA).
This final rule removes the specified test for the presence of
Mycoplasma to provide flexibility for accommodating new and evolving
technology and capabilities without diminishing public health
protections. Removal of this regulation allows manufacturers of live
virus vaccines produced from in vitro living cell cultures and
inactivated virus vaccines produced from such living cell cultures to
select the most scientifically appropriate Mycoplasma testing method to
assure the safety, purity, and potency of their vaccines.
These newer technologies can result in higher sensitivity and
specificity of Mycoplasma detection and could reduce the time required
to complete testing for Mycoplasma. Removal of this regulation does not
remove Mycoplasma testing requirements specified in individual BLAs. A
manufacturer of a live virus vaccine produced from in vitro living cell
cultures and inactivated virus vaccines produced from such living cell
cultures will continue to be required to follow the Mycoplasma test
requirements specified in its BLA, unless the BLA was revised to modify
or replace the test through a supplement in accordance with Sec.
601.12(c) (21 CFR 601.12(c)). FDA would review proposed changes to a
manufacturer's approved biologics license in the context of that
particular application to ensure that any such action is appropriate.
Although the final rule removes the regulation, a manufacturer
continues to be required to test for Mycoplasma as specified in its
BLA. This action provides regulated industry with flexibility, as
appropriate, to employ advances in science and technology as they
become available, without diminishing public health protections. As
appropriate, the Agency will describe the appropriate tests for
particular products in manufacturers' BLAs.
C. Summary of Comments to the Proposed Rule
We received comments on the proposed rule from individuals and
industry submitters. The comments were generally supportive, with some
comments suggesting new testing procedures be proposed. These comments
are further summarized in section IV.
III. Legal Authority
We are issuing this final 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, 331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360i, 371,
372, 374, and 381). 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 prevent
the
[[Page 51637]]
introduction, transmission, and spread of communicable disease.
IV. Comments on the Proposed Rule and FDA Response
A. Introduction
We received comments on the proposed rule from individuals and
industry submitters. We describe and respond to the comments in section
IV.B. We have combined comments on similar topics and have numbered
each comment to help distinguish between different comments. 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. Comments and FDA Response
(Comment 1) One comment requested that FDA not finalize the rule,
but instead amend the proposal to revoke the current test for
Mycoplasma. The commenter proposed that FDA include methodologies on
newer tests and how they are distinguishable from the present test;
comparable data on the accuracy of Mycoplasma detection between the
present and newer tests, and any other additional information that
would support FDA's argument that the newer tests are more efficient.
(Response 1) FDA interprets this comment to support the proposal to
remove the currently described methodology and to amend the regulation
to specify alternative acceptable tests. The purpose of this rulemaking
is to permit manufacturers of live virus vaccines produced from in
vitro living cell cultures and inactivated virus vaccines produced from
such living cell cultures to select the most scientifically appropriate
Mycoplasma testing method to assure the safety, purity, and potency of
their vaccines. Thus, FDA declines to amend the regulation to specify
alternative acceptable tests because this would not achieve the goal of
allowing flexibility, as appropriate, to employ advances in science and
technology as they become available without diminishing public health
protections. However, FDA acknowledges that guidance is helpful to
describe FDA's current thinking on alternative methods of testing for
Mycoplasma in manufacturing samples of live virus vaccines and
inactivated virus vaccines produced from in vitro living cell cultures.
FDA notes that recommended alternative methods for Mycoplasma testing
for viral vaccines are described in ``Guidance for Industry:
Characterization and Qualification of Cell Substrates and Other
Biological Materials Used in the Production of Viral Vaccines for
Infectious Disease Indications'' (February 2010) (https://www.fda.gov/media/78428/download).
(Comment 2) One comment supported the proposed rule.
(Response 2) We acknowledge and appreciate the supportive comment.
(Comment 3) One comment did not comment specifically on finalizing
the rule, but stated that with changes to technology, it makes sense to
update testing procedures. The comment stated that ``a list of the new
proposed test methods would be beneficial to compare the overall
benefits and disadvantages.'' Another comment suggested that if the
rule is finalized, FDA should provide guidance for alternative methods
of testing for Mycoplasma.
(Response 3) While the comment states that it would be helpful to
have a list of new proposed test methods, FDA does not believe the
regulation should be amended to include such a list because that list
could become outdated. License holders are welcome to discuss with FDA
proposals to change their existing test methods and to submit proposals
to FDA to revise the current test methods in use.
FDA also acknowledges that guidance is helpful to describe FDA's
current thinking on acceptable alternative methods of testing for
Mycoplasma in manufacturing samples of live virus vaccines and
inactivated virus vaccines produced from in vitro living cell cultures.
FDA notes that recommended alternative methods for Mycoplasma testing
for viral vaccines are described in ``Guidance for Industry:
Characterization and Qualification of Cell Substrates and Other
Biological Materials Used in the Production of Viral Vaccines for
Infectious Disease Indications'' (February 2010) (https://www.fda.gov/media/78428/download).
(Comment 4) One comment strongly supported removal of the
regulation and agreed that more sensitive test methods exist; however,
the commenter wanted the scope of the impact to be expanded to include
all biological product manufacturers.
(Response 4) We acknowledge and appreciate the supportive comment.
The request to expand the revocation to include all biological product
manufacturers is beyond the scope of this rule making because Sec.
610.30 pertains to manufacturers of live virus vaccines and inactivated
virus vaccines produced from in vitro living cell cultures.
V. Effective Date
The final rule will become effective 30 days after the date of
publication in the Federal Register.
VI. Economic Analysis of Impacts
A. Introduction
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.'' We
believe that this final rule is not a 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 this rule would increase flexibility and does not add
any new regulatory responsibilities, 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 $154
million, using the most current (2018) 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.
B. Summary of Costs and Benefits
This final rule will amend the biologics regulations under Sec.
610.30 by removing the specified test for Mycoplasma in the production
of live virus vaccines produced from in vitro living cell cultures and
inactivated virus
[[Page 51638]]
vaccines produced from such living cell cultures.
Removing the Sec. 610.30 Test for Mycoplasma will provide
manufacturers with the flexibility to determine the most appropriate
and effective Mycoplasma testing methods. FDA guidance dated after
Sec. 610.30, codified in 1973 (November 20, 1973, 38 FR 32056),
outlines up-to-date scientific practices to identify Mycoplasma in
production of live virus vaccines produced from in vitro living cell
cultures and inactivated virus vaccines produced from in vitro living
cell cultures. In practice, a vaccine manufacturer can change its
procedures at any time with submission and prior approval of a
supplement to its BLA. As a result, we do not expect the repeal of the
Sec. 610.30 Test for Mycoplasma to significantly influence the
behavior or procedures of vaccine manufacturers.
Because manufacturers already have the ability to pursue
alternative testing procedures, we anticipate no measurable change in
industry or FDA behavior from this final rulemaking. We therefore
expect the elimination of the Sec. 610.30 Test for Mycoplasma to be
cost neutral. This final rule will therefore produce no quantifiable
savings, costs, or transfers. We also expect no public health benefits
to be lost as a result of this revocation. Finally, we note that this
final rulemaking may drive some manufacturers to streamline their
procedures and search for more efficient Mycoplasma testing methods.
This optimization may produce some unquantifiable efficiencies.
Table 1--Summary of Benefits, Costs and Distributional Effects of Final Rule
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Units
Primary Low High ---------------------------------------
Category estimate estimate estimate Year Discount Period Notes
dollars rate (%) covered
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Benefits:
Annualized........................... ........... ........... ........... ........... 7 ...............................
Monetized $millions/year............. ........... ........... ........... ........... 3 ...............................
Annualized........................... ........... ........... ........... ........... 7 ...............................
Quantified........................... ........... ........... ........... ........... 3 ...............................
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Qualitative.......................... Benefits to manufacturers from ........... ........... ...............................
flexibility to determine appropriate
and effective Mycoplasma testing
methods.
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Costs:
Annualized........................... ........... ........... ........... ........... 7 ...............................
Monetized $millions/year............. ........... ........... ........... ........... 3 ...............................
Annualized........................... ........... ........... ........... ........... 7 ...............................
Quantified........................... ........... ........... ........... ........... 3 ...............................
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Qualitative.......................... Costs to manufacturers to change ........... ........... ...............................
Mycoplasma testing methods, if
voluntarily pursued.
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Transfers:
Federal.............................. ........... ........... ........... ........... 7 ...............................
Annualized........................... ........... ........... ........... ........... 3 ...............................
Monetized $millions/year............. ........... ........... ........... ........... ........... ...............................
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From/To.............................. From:
To:
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Other................................ ........... ........... ........... ........... 7 ...............................
Annualized........................... ........... ........... ........... ........... 3 ...............................
Monetized $millions/year............. ........... ........... ........... ........... ........... ...............................
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From/To.............................. From:
To:
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Effects:
State, Local or Tribal Government: None.
Small Business: None.
Wages: None.
Growth: None.
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In line with Executive Order 13771, in table 2 we present
annualized values of costs and cost savings over an infinite time
horizon. There are no quantifiable costs or cost savings from this
rule. This final rule would be considered a deregulatory action under
Executive Order 13771.
[[Page 51639]]
Table 2--Executive Order 13771 Summary Table
[in $ Millions 2016 Dollars, Over an Infinite Time Horizon]
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Primary Lower Upper
Item estimate (7%) estimate (7%) estimate (7%)
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Present Value of Costs.......................................... .............. .............. ..............
Present Value of Cost Savings................................... .............. .............. ..............
Present Value of Net Costs...................................... .............. .............. ..............
Annualized Costs................................................ .............. .............. ..............
Annualized Cost Savings......................................... .............. .............. ..............
Annualized Net Costs............................................ .............. .............. ..............
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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 25.31(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.
VIII. 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.
IX. Federalism
We have analyzed this final rule in accordance with the principles
set forth in Executive Order 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.
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
tribal summary impact statement is not required.
XI. Reference
The following reference is on display at the Dockets Management
Staff (see ADDRESSES) and is available for viewing by interested
persons between 9 a.m. and 4 p.m. Monday through Friday; it is also
available electronically at https://www.regulations.gov. FDA has
verified the website address, as of the date this document publishes in
the Federal Register, but websites are subject to change over time.
1. FDA/Economics Staff, ``Elimination of the 21 CFR 610.30 Test for
Mycoplasma Preliminary Regulatory Impact Analysis, Preliminary
Regulatory Flexibility Analysis, Unfunded Mandates Reform Act
Analysis,'' 2018. (Available at https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.)
List of Subjects in 21 CFR part 610
Biologics, Labeling, 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
610 is amended as follows:
PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS
0
1. The authority citation for part 610 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a,
264.
Subpart D--[Removed and Reserved]
0
2. Remove and reserve subpart D, consisting of Sec. 610.30.
Dated: July 29, 2020.
Stephen M. Hahn,
Commissioner of Food and Drugs.
[FR Doc. 2020-17085 Filed 8-20-20; 8:45 am]
BILLING CODE 4164-01-P