[Federal Register Volume 66, Number 186 (Tuesday, September 25, 2001)]
[Notices]
[Pages 49029-49030]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-23981]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01D-0361]


International Conference on Harmonisation; Draft Guidance on ICH 
Q1D Bracketing and Matrixing Designs for Stability Testing of Drug 
Substances and Drug Products; 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availability of a draft guidance entitled ``Q1D Bracketing and 
Matrixing Designs for Stability Testing of Drug Substances and Drug 
Products.'' The draft guidance was prepared under the auspices of the 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 This draft 
guidance is an annex to an ICH draft guidance entitled ``Q1A(R) 
Stability Testing of New Drug Substances and Products,'' that published 
in the Federal Register of April 21, 2000 (65 FR 21446). ICH Q1D is 
intended to provide guidance on the application of reduced designs 
(i.e., bracketing and matrixing) for stability studies conducted in 
accordance with the principles outlined in ICH Q1A(R).

DATES: Submit written or electronic comments on the draft guidance by 
November 26, 2001.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Drug Information Branch (HFD-210), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857; or the Office of Communication, Training, 
and Manufacturers Assistance (HFM-40), Center for Biologics Evaluation 
and Research (CBER), 1401 Rockville Pike, Rockville, MD 20852-1448, 
301-827-3844, FAX 888-CBERFAX. Send two self-addressed adhesive labels 
to assist the office in processing your requests. Submit written 
comments on the draft guidance to the Dockets Management Branch (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Chi-wan Chen, Center for Drug Evaluation 
and Research (HFD-830), Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, 301-827-2001, or Andrew Shrake, Center for 
Biologics Evaluation and Research (HFM-345), Food and Drug 
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448, 301-402-4635.
    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

[[Page 49030]]

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, 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), 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, FDA no longer includes the text of ICH 
guidances in the Federal Register. Instead, the agency publishes a 
notice in the Federal Register announcing the availability of an ICH 
guidance. The ICH guidance will be placed in the docket and can be 
obtained through regular agency sources (see the ADDRESSES section). 
Draft guidances will be left in the original ICH format. The final 
guidance will be reformatted to conform to the GGP style before 
publication.
    In November 2000, the ICH Steering Committee agreed that an ICH 
draft guidance entitled ``Q1D Bracketing and Matrixing Designs for 
Stability Testing of New Drug Substances and Drug Products'' should be 
made available for public comment. The draft guidance is the product of 
the Quality Expert Working Group of the ICH. Comments about this draft 
will be considered by FDA and the Quality Expert Working Group.
    ICH Q1A(R) notes that, if justified, the use of two types of 
reduced stability study designs (i.e., bracketing and matrixing) can be 
applied to the testing of new drug substances and products, but ICH 
Q1A(R) provides no further guidance on the subject. This draft guidance 
(ICH Q1D) describes the principles for applying bracketing or matrixing 
in situations where further justification is or is not important. 
Design factors and other considerations are presented, and potential 
risks of using reduced designs are discussed. Sample designs are 
provided as illustrations.
    This draft guidance represents the agency's current thinking on 
reduced stability testing of new drug substances and products. 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 draft guidance by November 26, 
2001. 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 
draft guidance and received comments are available for public 
examination in the Dockets Management Branch 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.fda.gov/cder/guidance/index.htm or http://www.fda.gov/cber/publications.htm.

    Dated: September 18, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-23981 Filed 9-24-01; 8:45 am]
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