[Federal Register Volume 66, Number 135 (Friday, July 13, 2001)]
[Notices]
[Pages 36791-36792]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-17498]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-1407]


International Conference on Harmonisation; Guidance on S7A Safety 
Pharmacology Studies for Human 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 guidance entitled ``S7A Safety Pharmacology Studies 
for Human Pharmaceuticals.'' The guidance was prepared under the 
auspices of the International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH). 
The guidance provides a definition, general principles, and 
recommendations for the nonclinical safety pharmacology studies. The 
guidance is intended to help protect clinical trial participants and 
patients receiving marketed products from potential adverse effects of 
pharmaceuticals, while avoiding unnecessary use of animals and other 
resources.

DATES: This guidance is effective August 13, 2001. Submit written 
comments at any time.

ADDRESSES: Submit written requests for single copies of the guidance to 
the Division of Drug Information (HFD-240), Center for Drug Evaluation 
and Research, Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857. Single copies of the recommendations may be 
obtained by mail from the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and 
Research (CBER), or by calling the CBER Voice Information System at 1-
800-835-4709 or 301-827-1800. Copies may be obtained from CBER's FAX 
Information System at 1-888-CBER-

[[Page 36792]]

FAX or 301-827-3844. Send two self-addressed adhesive labels to assist 
the office in processing your requests. Submit written comments on the 
guidance to the Dockets Management Branch (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. 
Requests and comments should be identified with the docket number found 
in brackets in the heading of this document. See the SUPPLEMENTARY 
INFORMATION section of this document for electronic access to the 
guidance.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance:
    Joseph J. DeGeorge, Center for Drug Evaluation and Research (HFD-
024), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 
20857, 301-594-5476, or
    Martin D. Green, Division of Clinical Trials and Design, Center for 
Biologics Evaluation and Research (HFM-579), 1401 Rockville Pike, 
Rockville, MD 20852, 301-827-5349,
    Regarding the ICH:
    Janet J. Showalter, Office of Health Affairs (HFY-20), Food and 
Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-
0864.

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 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, the Canadian Health Protection Branch, and the 
European Free Trade Area.
    In accordance with FDA's good guidance practices (GGPs) regulation 
(21 CFR 10.115; 65 FR 56468, September 19, 2000), this document is 
being called a guidance, rather than a guideline.
    To facilitate the process of making ICH guidances available to the 
public, the agency has changed its procedure for publishing ICH 
guidances. As of April 2000, we no longer include the text of ICH 
guidances in the Federal Register. Instead, we publish a notice in the 
Federal Register announcing the availability of an ICH guidance. The 
ICH guidance is placed in the docket and can be obtained through 
regular agency sources (see the ADDRESSES section). Draft guidances are 
left in the original ICH format. The final guidance is reformatted to 
conform to the GGP style before issuance.
    In the Federal Register of August 7, 2000 (65 FR 48246), FDA 
published a notice of availability for a draft tripartite guidance 
entitled ``S7A Safety Pharmacology Studies for Human Pharmaceuticals.'' 
The notice gave interested persons an opportunity to submit comments by 
September 6, 2000.
    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 2000.
    The guidance describes general principles and recommendations for 
safety pharmacology evaluations. The guidance is intended to help 
protect clinical trial participants and patients receiving marketed 
products from potential adverse reactions to pharmaceuticals and avoid 
unnecessary use of animals and other resources. The guidance generally 
applies to new chemical entities and biotechnology-derived products for 
human use. The guidance may be applied to marketed pharmaceuticals when 
appropriate. For example, adverse clinical events, a new patient 
population, or a new route of administration may raise concerns not 
previously addressed.
    The guidance incorporates the following changes:
    1. The guidance recommends that in the absence of a safety 
pharmacology response, the highest tested dose should be a dose 
associated with moderate toxicity. The draft guidance recommended that 
the highest dose tested should equal or exceed those doses producing 
some adverse effects.
    2. The guidance recommends that, in addition to respiratory rate, 
other measures of respiratory function (e.g., tidal volume or 
hemoglobin oxygen saturation) should be evaluated in assessing effects 
of the test substance on the respiratory system.
    3. Concerning the application of good laboratory practice (GLP), 
the guidance clarifies that secondary pharmacodynamic studies that 
contribute to the safety evaluation should be conducted in compliance 
with GLP.
    This 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 Dockets Management Branch 
(address above) written comments on the guidance at any time. Two 
copies of any comments are to be submitted, except that individuals may 
submit one copy. Comments are to be identified with the docket number 
found in brackets in the heading of this document. The guidance and 
received comments may be seen in the office above between 9 a.m. and 4 
p.m., Monday through Friday.

III. Electronic Access

    Persons with access to the Internet can obtain the guidance at 
http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/cber/publications.htm.

    Dated: July 6, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-17498 Filed 7-12-01; 8:45 am]
BILLING CODE 4160-01-S