
[Federal Register Volume 77, Number 110 (Thursday, June 7, 2012)]
[Notices]
[Pages 33748-33749]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-13774]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0178]


International Conference on Harmonisation; Guidance on S2(R1) 
Genotoxicity Testing and Data Interpretation for Pharmaceuticals 
Intended for Human Use; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance entitled ``S2(R1) Genotoxicity Testing and 
Data Interpretation for Pharmaceuticals Intended for Human Use'' (ICH 
S2(R1)). This guidance was prepared under the auspices of the 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH). The ICH S2(R1) 
combines and replaces two ICH guidances, ``S2A Specific Aspects for 
Regulatory Genotoxicity Tests for Pharmaceuticals'' and ``S2B 
Genotoxicity: A Standard Battery for Genotoxicity Testing of 
Pharmaceuticals.'' ICH S2(R1) provides guidance to drug sponsors on 
which tests should be performed to assess potential genotoxicity of 
pharmaceuticals. It also provides guidance on testing conditions, data 
interpretation, and followup strategies if a positive response is seen 
in in vitro assays. This guidance is intended to provide drug sponsors 
with recommendations to ensure that drugs are appropriately tested for 
potential to cause genetic damage and to ensure efficient development 
of new drugs.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of the guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 2201, Silver Spring, MD 20993-0002, or the Office of 
Communication, Outreach and Development (HFM-40), Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 1401 
Rockville Pike, suite 200N, Rockville, MD 20852-1448. Send one self-
addressed adhesive label to assist the office in processing your 
requests. The guidance may also be obtained by mail by calling CBER at 
1-800-835-4709 or 301-827-1800. See the SUPPLEMENTARY INFORMATION 
section for electronic access to the guidance document.
    Submit electronic comments on the 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

    David Jacobson-Kram, Center for Drug Evaluation and Research, Food 
and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6488,

[[Page 33749]]

Silver Spring, MD 20993-0002, 301-796-0175.

Regarding the ICH

    Michelle Limoli, Office of International Programs, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 31, Rm. 3506, Silver 
Spring, MD 20993-0002, 301-796-4600.

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: The European Union, Japan, 
and the United States. The six 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; the Centers for Drug 
Evaluation and Research and Biologics Evaluation and Research, FDA; and 
the Pharmaceutical Research and Manufacturers of America. 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, Health Canada, and the European Free Trade Area.
    In the Federal Register of March 26, 2008 (73 FR 16024), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``S2(R1) Genotoxicity Testing and Data Interpretation for 
Pharmaceuticals Intended for Human Use.'' The notice gave interested 
persons an opportunity to submit comments by May 12, 2008.
    After consideration of the comments received and revisions to the 
guidance, a final draft of the guidance was submitted to the ICH 
Steering Committee and endorsed by the three participating regulatory 
Agencies in November 2011.
    The purpose of the ICH S2(R1) revision is to provide guidance on 
optimizing the standard genetic toxicology battery for prediction of 
potential human risks, and on interpreting results, with the goal of 
improving risk characterization for carcinogenic effects that have 
their basis in changes in the genetic material. The revised guidance 
describes internationally agreed-upon standards for followup testing 
and interpretation of positive results in vitro and in vivo in the 
standard genetic toxicology battery, including assessment of 
nonrelevant findings.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
Agency's current thinking on this topic. It does not create or confer 
any rights for or on any person and does not operate to bind FDA or the 
public. An alternative approach may be used if such approach satisfies 
the requirements of the applicable statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of mailed 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.

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: June 1, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-13774 Filed 6-6-12; 8:45 am]
BILLING CODE 4160-01-P


