[Federal Register: September 3, 2008 (Volume 73, Number 171)]
[Notices]               
[Page 51491-51492]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03se08-81]                         


[[Page 51491]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0470]

 
International Conference on Harmonisation; Draft Guidance on 
M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical 
Trials and Marketing Authorization for Pharmaceuticals; 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availability of a draft guidance entitled ``M3(R2) Nonclinical Safety 
Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals.'' The draft guidance was prepared 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). The draft guidance, which is a revision of an existing 
guidance, discusses the types of nonclinical studies, their scope and 
duration, and their relation to the conduct of human clinical trials 
and marketing authorization for pharmaceuticals. The draft guidance is 
intended to facilitate the timely conduct of clinical trials and reduce 
the unnecessary use of animals and other drug development resources.

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this draft guidance before it begins work on the final version of the 
guidance, submit written or electronic comments on the draft guidance 
by October 20, 2008.

ADDRESSES:  Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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, 10903 New 
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send 
two self-addressed adhesive labels to assist the office in processing 
your requests. Submit written comments on the draft guidance to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic 
comments to http://www.regulations.gov. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance 
document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Abigail Jacobs, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, rm. 6484, Silver Spring, MD, 20993-0002, 301-796-0174, or 
Martin D. Green, Center for Biologics Evaluation and Research (HFM-
475), Food and Drug Administration, 1401 Rockville Pike, suite 200N, 
Rockville, MD 20852-1448, 301-827-3070.
    Regarding the ICH: Michelle Limoli, Office of International 
Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-4480.

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 June 2008, the ICH Steering Committee agreed that a draft 
guidance entitled ``M3(R2) Nonclinical Safety Studies for the Conduct 
of Human Clinical Trials and Marketing Authorization for 
Pharmaceuticals'' should be made available for public comment. The 
draft guidance is the product of the Multidisciplinary Safety and 
Efficacy (M3) Expert Working Group of the ICH. Comments about this 
draft will be considered by FDA and the M3 Expert Working Group.
    The purpose of the draft guidance is to recommend international 
standards for, and promote harmonization of, the nonclinical safety 
studies recommended to support human clinical trials of a given scope 
and duration. The revisions in this draft guidance further harmonize 
the recommendations in a number of areas and include a new section on 
exploratory clinical studies. The recommendations should promote safe 
and ethical development and availability of new pharmaceuticals.
    The document provides guidance on nonclinical safety studies and 
their relation to the conduct of human clinical trials and marketing of 
a pharmaceutical, primarily addressing timing. The discussion includes 
safety pharmacology studies, repeated dose toxicity studies, 
toxicokinetic and nonclinical pharmacokinetic studies, reproduction 
toxicity studies, genotoxicity studies, and (for drugs that have 
special cause for concern or are intended for a long duration of use) 
an assessment of carcinogenic potential. The draft guidance discusses 
other nonclinical studies that should be conducted on a case-by-case 
basis as appropriate, including phototoxicity studies, immunotoxicity 
studies, juvenile animal toxicity studies, and abuse potential studies.
    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 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) written or electronic comments on the draft guidance. 
Submit a single copy of electronic comments or

[[Page 51492]]

two paper copies of any mailed comments, except that individuals may 
submit one paper copy. Comments are to be identified 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.
    Please note that on January 15, 2008, the FDA Division of Dockets 
Management Web site transitioned to the Federal Dockets Management 
System (FDMS). FDMS is a Government-wide, electronic docket management 
system. Electronic comments or submissions will be accepted by FDA only 
through FDMS 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/cder/guidance/index.htm, 
or http:www/fda.gov/cber/guidelines.htm.

    Dated: August 26, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-20294 Filed 9-2-08; 8:45 am]

BILLING CODE 4160-01-S