[Federal Register Volume 80, Number 187 (Monday, September 28, 2015)]
[Notices]
[Pages 58261-58262]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-24510]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-D-0369]


M7(R1) Addendum to ICH M7; International Conference on 
Harmonisation; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance entitled ``M7(R1) Addendum to ICH 
M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in 
Pharmaceuticals to Limit Potential Carcinogenic Risk; Application of 
the Principles of the ICH M7 Guidance to Calculation of Compound-
Specific Acceptable Intakes.'' The draft guidance was prepared under 
the auspices of the International Conference on Harmonisation of 
Technical Requirements for Registration of Pharmaceuticals for Human 
Use (ICH). This draft guidance, an addendum to the ICH M7 guidance of 
May 28, 2015, provides guidance on acceptable intake limits derived for 
some chemicals that are considered to be mutagens and carcinogens, and 
that were selected because they are commonly used in pharmaceutical 
manufacturing or are useful in illustrating the principles for deriving 
compound-specific intakes as described in ICH M7. The draft

[[Page 58262]]

guidance is intended to provide guidance for new drug substances and 
new drug products during their clinical development and subsequent 
applications for marketing.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115 (g)(5)), to ensure that the Agency considers your comment on 
this draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by November 27, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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 
the office in processing your requests. The draft 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 
draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Aisar 
Atrakchi, Center for Drug Evaluation and Research, Food and Drug 
Administration, Bldg. 22, Rm. 4118, Silver Spring, MD 20993-0002, 301-
796-1036; or Anne Pilaro, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
4025, Silver Spring, MD 20993-0002, 240-402-8341.
    Regarding the ICH: Michelle Limoli, Center for Drug Evaluation and 
Research, International Programs, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7208, Silver Spring, MD 20993-0002, 
301-796-8377.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for tripartite 
harmonization initiatives to be developed with input from both 
regulatory and industry representatives. FDA also seeks input from 
consumer representatives and others. ICH is concerned with 
harmonization of technical requirements for the registration of 
pharmaceutical products among three regions: Europe, Japan, and North 
America. The eight ICH sponsors are the European Commission; the 
European Federation of Pharmaceutical Industries Associations; the 
Japanese Ministry of Health, Labour, and Welfare; the Japanese 
Pharmaceutical Manufacturers Association; CDER and CBER, FDA; the 
Pharmaceutical Research and Manufacturers of America; Health Canada; 
and Swissmedic. The ICH Secretariat, which coordinates the preparation 
of documentation, is provided by the International Federation of 
Pharmaceutical Manufacturers Associations (IFPMA).
    The ICH Steering Committee includes representatives from each of 
the ICH sponsors and the IFPMA, as well as observers from the World 
Health Organization.
    In June 2015, the ICH Steering Committee agreed that the following 
draft guidance should be made available for public comment: ``M7(R1) 
Addendum to ICH M7: Assessment and Control of DNA Reactive (Mutagenic) 
Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk; 
Application of the Principles of the ICH M7 Guidance to Calculation of 
Compound-Specific Acceptable Intakes.'' The draft guidance is the 
product of the Expert Working Group of the ICH. Comments about this 
draft will be considered by FDA and the Expert Working Group.
    The draft guidance provides guidance on acceptable intake limits 
derived for some chemicals that are considered to be mutagens and 
carcinogens and that were selected because they are commonly used in 
pharmaceutical manufacturing or are useful in illustrating the 
principles of deriving compound-specific intakes as described in ICH 
M7. The default method from ICH M7 of linear extrapolation from the 
cancer potency estimate, TD50, is used as the primary method 
to derive the acceptable intakes for carcinogens with likely mutagenic 
mode of action.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on this topic. 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. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.regulations.gov, http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

    Dated: September 22, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-24510 Filed 9-25-15; 8:45 am]
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