```

[Federal Register Volume 87, Number 67 (Thursday, April 7, 2022)]
[Notices]
[Pages 20435-20436]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-07395]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-0055]

M7(R2) Addendum: Application of the Principles of the ICH M7 
Guideline to Calculation of Compound-Specific Acceptable Intakes; 
International Council for Harmonisation; Draft Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is 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the availability of a draft guidance for industry entitled ``M7(R2) 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; International 
Council for Harmonisation; Draft Guidance for Industry.'' The draft 
guidance was prepared under the auspices of the International Council 
for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH). The draft guidance adds monographs for seven new 
compounds to the M7 Guideline which outlines considerations for 
assessment and control of DNA reactive (mutagenic) impurities to limit 
potential carcinogenic risk. The compounds are: Acetaldehyde, 
dibromoethane, epichlorohydrin, ethyl bromide, formaldehyde, styrene, 
and vinyl acetate. The addendum is intended to update the M7 Guideline 
in line with the ICH process for its maintenance and includes other 
revisions.

DATES: Submit either electronic or written comments on the draft 
guidance by May 9, 2022 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2022-D-0055 for ``M7(R2) Addendum: Application of the Principles of 
the ICH M7 Guideline to Calculation of Compound-Specific Acceptable 
Intakes.'' 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: 

[[Page 20436]]

    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

    The Food and Drug Administration (FDA or Agency) is 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; International 
Council for Harmonisation; Draft Guidance for Industry.'' 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 the 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, the 
Membership of ICH has expanded to include other regulatory authorities 
and industry associations from around the world (refer to 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 September 2021, the ICH Assembly endorsed the draft guideline 
entitled ``M7(R2) Addendum: Application of the Principles of the ICH M7 
Guideline to Calculation of Compound-Specific Acceptable Intakes'' 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 guidance adds monographs for seven new compounds to the 
M7 Guideline which outlines considerations for assessment and control 
of DNA reactive (mutagenic) impurities to limit potential carcinogenic 
risk. The compounds are: Acetaldehyde, dibromoethane, epichlorohydrin, 
ethyl bromide, formaldehyde, styrene, and vinyl acetate. The addendum 
is intended to update the M7 Guideline in line with the ICH process for 
its maintenance and includes other revisions.
    This draft guidance has been left in the original ICH format. It 
contains only a list of revisions to the M7(R1) Guideline as well as 
the monographs for seven new compounds submitted for public 
consultation. The final guidance will include a complete, integrated 
M7(R2) Guideline and Addendum and 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(R2) Assessment and Control of DNA Reactive 
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential 
Carcinogenic Risk'' and its Addendum. 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 this draft 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 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/regulatory-information/search-fda-guidance-documents, 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: April 1, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-07395 Filed 4-6-22; 8:45 am]
BILLING CODE 4164-01-P
```