[Federal Register Volume 85, Number 189 (Tuesday, September 29, 2020)]
[Notices]
[Pages 61009-61011]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-21461]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-1790]


M7 Assessment and Control of Deoxyribonucleic Acid Reactive 
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential 
Carcinogenic Risk--Questions and Answers; International Council for 
Harmonisation; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``M7 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 The draft guidance was prepared under the auspices of the 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH), formerly the International 
Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use. The draft guidance provides a 
practical approach that is applicable to the identification, 
categorization, qualification, and control of mutagenic impurities to 
limit potential carcinogenic risk. Since the ICH M7 Guideline was 
finalized, the worldwide experience with implementation of the 
recommendations for DNA reactive (mutagenic) impurities has given rise 
to requests for clarification relating to the assessment and control of 
DNA reactive (mutagenic) impurities. To facilitate the implementation 
of the ICH M7 Guideline, the ICH M7 Implementation Working Group has 
developed a series of questions and answers (Q&As). The scope of this 
draft Q&A guidance follows that of the ICH M7 Guideline. The draft Q&A 
guidance is intended to clarify, promote the convergence of, and 
improve the harmonization of the considerations for assessment and 
control of DNA reactive (mutagenic) impurities and of the information 
that should be provided when developing

[[Page 61010]]

drugs, completing marketing authorization applications, and using drug 
master files.

DATES: Submit either electronic or written comments on the draft 
guidance by December 28, 2020 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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-2020-N-1790 for ``M7 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 Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 4118, Silver Spring, MD 20993-0002, 301-796-1036; or 
Stephen Ripley, Center for Biologics Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, 
Silver Spring, MD 20993-0002, 240-402-7911.
    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 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 draft guidance was prepared under the 
auspices of ICH. ICH has the mission of achieving 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 have substantially reduced duplicative clinical 
studies, prevented unnecessary animal studies, standardized the 
reporting of important safety information, standardized marketing 
application submissions, and made many other improvements in the 
quality of global drug development and manufacturing and the products 
available to patients.
    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. Additionally,

[[Page 61011]]

the Membership of ICH has expanded to include other regulatory 
authorities and industry associations from around the world (https://www.ich.org/).
    ICH works by involving technical experts from both regulators and 
industry parties in detailed technical harmonization work and the 
application of a science-based approach to harmonization through a 
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 June 2020, the ICH Assembly endorsed the draft guideline 
entitled ``M7 Assessment and Control of DNA Reactive (Mutagenic) 
Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk--
Questions and Answers'' and agreed that the guideline should be made 
available for public comment. The draft guideline is the product of the 
Safety Expert Working Group of the ICH. Comments about this draft will 
be considered by FDA and the Safety Expert Working Group.
    The draft Q&A guidance is intended to clarify, promote the 
convergence of, and improve the harmonization of the considerations for 
assessment and control of DNA reactive (mutagenic) impurities and of 
the information that should be provided when developing drugs, 
completing marketing authorization applications, and using drug master 
files. This is important because since the ICH M7 Guideline was 
finalized, the worldwide experience with implementation of the 
recommendations for DNA reactive (mutagenic) impurities has given rise 
to requests for clarification relating to the assessment and control of 
DNA reactive (mutagenic) impurities. To facilitate the implementation 
of the ICH M7 Guideline, the ICH M7 Implementation Working Group has 
developed a series of Q&As. The scope of this draft Q&A guidance 
follows that of the ICH M7 Guideline.
    This draft guidance has been left in the original ICH format. The 
final guidance will be reformatted and edited to conform with FDA's 
good guidance practices regulation (21 CFR 10.115) and style before 
publication. The draft guidance, when finalized, will represent the 
current thinking of FDA on ``M7 Assessment and Control of DNA Reactive 
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential 
Carcinogenic Risk--Questions and Answers.'' 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

    FDA tentatively concludes that this draft guidance contains no 
collection 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.
    However, this draft guidance refers to previously approved FDA 
collections of information. These collections of information are 
subject to review by OMB under the PRA. The collections of information 
in 21 CFR part 601 has been approved under OMB control number 0910-
0338. The collections of information in 21 CFR parts 312 and 314 have 
been approved under OMB control numbers 0910-0014 and 0910-0001, and 
the collection of information under 21 CFR parts 210 and 211 have been 
approved under OMB control number 0910-0139.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.

    Dated: September 22, 2020.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2020-21461 Filed 9-28-20; 8:45 am]
BILLING CODE 4164-01-P