[Federal Register Volume 88, Number 141 (Tuesday, July 25, 2023)]
[Notices]
[Pages 47886-47888]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-15645]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA-2022-D-0055 and FDA-2020-N-1790]
M7(R2) Assessment and Control of Deoxyribonucleic Acid Reactive
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential
Carcinogenic Risk, M7(R2) Addendum, and M7(R2) Questions and Answers;
International Council for Harmonisation; Guidances for Industry;
Availability
AGENCY: Food and Drug Administration, HHS.
[[Page 47887]]
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled ``M7(R2)
Assessment and Control of DNA Reactive (Mutagenic) Impurities in
Pharmaceuticals to Limit Potential Carcinogenic Risk'' (M7(R2)
Guidance) and two supplemental documents entitled ``M7(R2) Addendum:
Application of the Principles of the ICH M7 Guidance to Calculation of
Compound-Specific Acceptable Intakes'' (M7(R2) Addendum) and ``M7(R2)
Assessment and Control of DNA Reactive (Mutagenic) Impurities in
Pharmaceuticals to Limit Potential Carcinogenic Risk Questions and
Answers'' (M7(R2) Questions and Answers). The M7(R2) Guidance, M7(R2)
Addendum, and M7(R2) Questions and Answers were prepared under the
auspices of the International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use (ICH). The guidance and
supplemental documents are intended to harmonize the considerations for
assessment and control of DNA reactive (mutagenic) impurities. The
M7(R2) Guidance and M7(R2) Addendum replace the guidance for industry
entitled ``M7(R1) Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk,''
issued on March 14, 2018. The M7(R2) Guidance, M7(R2) Addendum, and
M7(R2) Questions and Answers, also finalize the draft guidances for
industry entitled ``M7(R2) Addendum: Application of the Principles of
the ICH M7 Guideline to Calculation of Compound-Specific Acceptable
Intakes'' and ``M7 Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk--
Questions and Answers'' issued on April 7, 2022, and September 29,
2020, respectively.
DATES: The announcement of the guidance is published in the Federal
Register on July 25, 2023.
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:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
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 https://www.regulations.gov.
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:
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.
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-2022-D-0055 for ``M7(R2) Assessment and Control of DNA Reactive
(Mutagenic) Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk,'' and ``M7(R2) Addendum: Application of the
Principles of the ICH M7 Guidance to Calculation of Compound-Specific
Acceptable Intakes,'' or Docket No. FDA-2020-N-1790 for ``M7(R2)
Assessment and Control of DNA Reactive (Mutagenic) Impurities in
Pharmaceuticals to Limit Potential Carcinogenic Risk Questions and
Answers.'' Received comments will be placed in the docket and, except
for those submitted as ``Confidential Submissions,'' publicly viewable
at https://www.regulations.gov or at the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
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 https://www.regulations.gov.
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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov 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 Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. The guidance may also be obtained by mail by calling
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT:
Regarding the guidance: Aisar Atrakchi, Center for Drug Evaluation
and Research, Food and Drug
[[Page 47888]]
Administration, 10904 New Hampshire Ave., Bldg. 22, Rm. 4118, Silver
Spring, MD 20993-0003, 301-769-1036.
Regarding the ICH: Jill Adleberg, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-5259,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``M7(R2) Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.''
The guidance was prepared under the auspices of ICH. ICH seeks to
achieve greater regulatory harmonization worldwide to ensure that safe,
effective, high-quality medicines are developed, registered, and
maintained in the most resource-efficient manner.
By harmonizing the regulatory requirements in regions around the
world, ICH guidelines enhance global drug development, improve
manufacturing standards, and increase the availability of medications.
For example, ICH guidelines have substantially reduced duplicative
clinical studies, prevented unnecessary animal studies, standardized
the reporting of important safety information, and standardized
marketing application submissions.
The six Founding Members of the ICH are FDA; the Pharmaceutical
Research and Manufacturers of America; the European Commission; the
European Federation of Pharmaceutical Industries Associations; the
Japanese Ministry of Health, Labour, and Welfare; and the Japanese
Pharmaceutical Manufacturers Association. The Standing Members of the
ICH Association include Health Canada and Swissmedic. ICH membership
continues to expand to include other regulatory authorities and
industry associations from around the world (refer to https://www.ich.org/).
ICH works by engaging global regulatory and industry experts in a
detailed, science-based, and consensus-driven process that results in
the development of ICH guidelines. The regulators around the world are
committed to consistently adopting these consensus-based guidelines,
realizing the benefits for patients and for industry.
As a Founding Regulatory Member of ICH, FDA plays a major role in
the development of each of the ICH guidelines, which FDA then adopts
and issues as guidance for industry. FDA's guidance documents do not
establish legally enforceable responsibilities. Instead, they describe
the Agency's current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory requirements
are cited.
In the Federal Register of April 7, 2022 (87 FR 20435), FDA
published a notice announcing the availability of a draft guidance for
industry entitled ``M7(R2) Addendum: Application of the Principles of
the ICH M7 Guideline to Calculation of Compound-Specific Acceptable
Intakes,'' which included ICH assembly approved changes, including the
separation of the main guidance and addendum into two separate
documents. In the Federal Register of September 29, 2020 (85 FR 61009),
FDA published a notice announcing the availability of a draft guidance
for industry entitled ``M7 Assessment and Control of DNA reactive
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential
Carcinogenic Risk--Questions and Answers.'' The notices gave interested
persons an opportunity to submit comments by May 9, 2022, and December
28, 2020, respectively.
After consideration of the comments received and revisions to the
guidances, final drafts of the guidance and supplemental documents were
submitted to the ICH Assembly and endorsed by the regulatory Agencies
on May 24, 2022, and April 3, 2023.
These guidances finalize the above draft guidances issued on April
7, 2022, and September 29, 2020, with no significant changes. The
M7(R2) Guidance is intended to be read in conjunction with two
accompaniment documents, the M7(R2) Addendum and the M7(R2) Questions
and Answers. The core M7(R2) Guidance includes information on mutagenic
impurities and changes to HIV treatment duration. The M7(R2) Addendum
contains monographs for mutagenic chemicals that are common in
pharmaceutical manufacturing or are useful to illustrate the principles
for deriving compound-specific intakes described in the core guidance.
The M7(R2) Questions and Answers facilitate consistent implementation
by clarifying issues and concerns identified since the first version of
the final guidance for industry, ``M7 Assessment and Control of DNA
Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk,'' published in 2014.
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 ``M7(R2) Assessment and Control of DNA
Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk.'' It does not establish any rights for any person
and 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.
II. Paperwork Reduction Act of 1995
While these guidances contains no collection of information, they
do 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 these guidances. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 601 have been approved under OMB control
number 0910-0338. The collections of information pertaining to 21 CFR
parts 312 and 314 have been approved under OMB control numbers 0910-
0014 and 0910-0001, respectively. The collections of information in 21
CFR parts 210 and 211 pertaining to current good manufacturing practice
requirements have been approved under OMB control number 0910-0139.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, or https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
Dated: July 19, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-15645 Filed 7-24-23; 8:45 am]
BILLING CODE 4164-01-P