Notice2022-22334
Comparability Protocols for Postapproval Changes to the Chemistry, Manufacturing, and Controls Information in a New Drug Application, Abbreviated New Drug Application, or Biologics License Application; Guidance for Industry; Availability
Primary source
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Published
October 14, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled "Comparability Protocols for Postapproval Changes to the Chemistry, Manufacturing, and Controls Information in an NDA, ANDA, or BLA." This final guidance is intended to assist original applicants and holders of approved new drug applications (NDAs), abbreviated new drug applications (ANDAs), and biologics license applications (BLAs) on implementing a chemistry, manufacturing, and controls (CMC) postapproval change(s) through the use of a comparability protocol (CP). In many cases, submission and approval of a CP will facilitate the subsequent implementation and reporting of CMC changes, which could result in moving a drug or biological product into distribution or facilitating a proactive approach to reinforcing the supply of a product sooner than if a CP were not used. This final guidance recommends a framework to promote continuous improvement in the manufacturing of quality drug and biological products. This document finalizes a revised draft guidance that published on April 20, 2016, entitled "Comparability Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and Controls Information." A related draft guidance entitled "Comparability Protocols--Protein Drug Products and Biological Products--Chemistry, Manufacturing, and Controls Information" that published in September 2003, was withdrawn on May 6, 2015.
Full Text
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<title>Federal Register, Volume 87 Issue 198 (Friday, October 14, 2022)</title>
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[Federal Register Volume 87, Number 198 (Friday, October 14, 2022)]
[Notices]
[Pages 62417-62419]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-22334]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-D-0973]
Comparability Protocols for Postapproval Changes to the
Chemistry, Manufacturing, and Controls Information in a New Drug
Application, Abbreviated New Drug Application, or Biologics License
Application; Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled
``Comparability Protocols for Postapproval Changes to the Chemistry,
Manufacturing, and Controls Information in an NDA, ANDA, or BLA.'' This
final guidance is intended to assist original applicants and holders of
approved new drug applications (NDAs), abbreviated new drug
applications (ANDAs), and biologics
[[Page 62418]]
license applications (BLAs) on implementing a chemistry, manufacturing,
and controls (CMC) postapproval change(s) through the use of a
comparability protocol (CP). In many cases, submission and approval of
a CP will facilitate the subsequent implementation and reporting of CMC
changes, which could result in moving a drug or biological product into
distribution or facilitating a proactive approach to reinforcing the
supply of a product sooner than if a CP were not used. This final
guidance recommends a framework to promote continuous improvement in
the manufacturing of quality drug and biological products. This
document finalizes a revised draft guidance that published on April 20,
2016, entitled ``Comparability Protocols for Human Drugs and Biologics:
Chemistry, Manufacturing, and Controls Information.'' A related draft
guidance entitled ``Comparability Protocols--Protein Drug Products and
Biological Products--Chemistry, Manufacturing, and Controls
Information'' that published in September 2003, was withdrawn on May 6,
2015.
DATES: The announcement of the guidance is published in the Federal
Register on October 14, 2022.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2016-D-0973 for ``Comparability Protocols for Postapproval Changes
to the Chemistry, Manufacturing, and Controls Information in an NDA,
ANDA, or BLA.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002 or the Center for
Biologics Evaluation and Research, Office of Communication, Outreach,
and Development, 10903 New Hampshire Ave., WO71, Room 3128, Silver
Spring, MD 20903. Send one self-addressed adhesive label to assist that
office in processing your requests. See the SUPPLEMENTARY INFORMATION
section for electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Stephen Moore, Center for Drug
Evaluation and Research, Food and Drug Administration, Bldg. 51, Rm.
4159, 10903 New Hampshire Ave., Silver Spring, MD, 20993-0002, 301-796-
7579 or Stephen Ripley, Center for Biologics Evaluation and Research,
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm.
7301, Silver Spring, MD 20993, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Comparability Protocols for Postapproval Changes to the
Chemistry, Manufacturing, and Controls Information in an NDA, ANDA, or
BLA.'' The final guidance is intended to assist original applicants and
holders of approved applications for human drugs and biological
products on implementing a CMC postapproval change(s) through the use
of a CP. In this guidance, a comparability protocol is synonymous with
a postapproval change management protocol in the International Council
for Harmonisation (ICH) Q12 guidance ``Technical and Regulatory
Considerations for Pharmaceutical Product Lifecycle Management'' (May
2021). The final guidance is not applicable to blood and blood
components; biological products that also meet the definition of a
device in section 201(h) of the Federal Food,
[[Page 62419]]
Drug, and Cosmetic Act; or human cells, tissues, or cellular or tissue-
based products regulated solely under section 361 of the Public Health
Service Act (42 U.S.C. 264) and 21 CFR part 1271.
On April 20, 2016, (81 FR 23303), FDA announced the availability of
a revised draft guidance entitled ``Comparability Protocols for Human
Drugs and Biologics: Chemistry, Manufacturing, and Controls
Information.'' This was a revised draft of a draft guidance published
in February 2003. We revised the February 2003 draft guidance in 2016
for the following reasons:
<bullet> To include current pharmaceutical quality concepts.
<bullet> To provide more flexibility regarding filing procedures
for a notification of modifications to an approved CP in less
burdensome reporting categories than a prior approval supplement.
<bullet> To add an appendix to address commonly asked questions.
The Center for Veterinary Medicine, which was included in the
February 2003 draft guidance, published recommendations for animal
drugs in a separate guidance.
We received a number of comments on the revised draft guidance,
which the Agency considered carefully as it prepared this final
guidance. Additional information has been included in the final
guidance on proposing an appropriate reporting category for
implementation of changes under a CP once approved. Additional examples
have been included for notification of modifications to an approved CP
in less burdensome reporting categories than a prior approval
supplement. Information has been included in the appendix on cross-
referencing of a master file, including a Drug Master File, in a CP and
submitting a CP to a master file. Also, the recommendations in the
guidance for industry ICH Q12 have been carefully considered when
revising this guidance to maximize consistency. We also have made
clarifications and editorial changes to the final guidance document.
This final guidance provides recommendations to original applicants
and holders of approved applications for human drugs and certain
biological products on implementing CMC postapproval change(s) through
the use of a CP. In many cases, submission and approval of a CP will
facilitate the subsequent implementation and reporting of CMC changes,
which could result in moving a drug or biological product into
distribution or facilitating a proactive approach to reinforcing the
supply of a product sooner than if a CP were not used.
The final guidance recommends a framework to promote continuous
improvement in the manufacturing of quality drug and biological
products by encouraging applicants to employ the following:
<bullet> Effective use of knowledge and understanding of the
product and manufacturing process;
<bullet> Risk management activities over the life cycle of a
product; and
<bullet> An effective pharmaceutical quality system
This final guidance incorporates the modern regulatory concepts
stated in the guidance for industry entitled ``PAT--A Framework for
Innovative Pharmaceutical Development, Manufacturing, and Quality
Assurance,'' the Pharmaceutical Quality for the 21st Century--A Risk
Based Approach, the Critical Path Initiative, and the quality by design
principles described in the guidance for industry entitled ``Q8(R2)
Pharmaceutical Development.''
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Comparability Protocols for Postapproval
Changes to the Chemistry, Manufacturing, and Controls Information in an
NDA, ANDA, or BLA.'' It does not establish any rights for any person
and, with the exception of section V, is not binding on FDA or the
public. You can use an alternative approach if it satisfies the
requirements of the applicable statutes and regulations.
As noted, insofar as section V of this guidance sets forth that
certain modifications to an approved CP must be submitted in a changes
being effected supplement or annual report rather than a prior approval
supplement, it has binding effect, as indicated by the use of the words
must, shall, or required. Such binding effect derives from section 506A
of the FD&C Act, as implemented in 21 CFR 314.70 and 601.12.
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 314 have been approved under OMB control
number 0910-0001. The collections of information in 21 CFR part 601
have been approved under OMB control number 0910-0338. The collections
of information in 21 CFR parts 210 and 211 relating to current good
manufacturing practices have been approved under OMB control number
0910-0139. The collections of information relating to section 351(k) of
the PHS Act have been approved under OMB control number 0910-0718.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
<a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: October 7, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-22334 Filed 10-13-22; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on October 14, 2022.
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