[Federal Register Volume 68, Number 11 (Thursday, January 16, 2003)]
[Notices]
[Pages 2339-2340]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-904]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01D-0361]


International Conference on Harmonisation; Guidance on Q1D 
Bracketing and Matrixing Designs for Stability Testing of New Drug 
Substances and 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 guidance entitled ``Q1D Bracketing and Matrixing 
Designs for Stability Testing of New Drug Substances and Products.'' 
The guidance was prepared under the auspices of the International 
Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use (ICH). This guidance is an annex to an 
ICH guidance entitled ``Q1A(R) Stability Testing of New Drug Substances 
and Products'' (66 FR 56332, November 7, 2001). It 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: The guidance is effective January 16, 2003. Submit written or 
electronic 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, or the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and 
Research (CBER), Food and Drug Administration, 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. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document. 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. 
Submit electronic comments to http://www.fda.gov/dockets/ecomments. 
Requests and comments should be identified with the docket number found 
in brackets in the heading of this 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, Rockville, MD 20852-1448, 301-402-
4635.
    Regarding the ICH: Janet Showalter, Office of International 
Programs (HFG-1), 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

[[Page 2340]]

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's Health Products and Food 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, 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 ADDRESSES). Draft guidances are left in the 
original ICH format. The final guidance is reformatted to conform to 
the GGP style before publication.
    In the Federal Register of September 25, 2001 (66 FR 49029), FDA 
published a draft tripartite guidance entitled ``Q1D Bracketing and 
Matrixing Designs for Stability Testing of Drug Substances and Drug 
Products.'' The notice gave interested persons an opportunity to submit 
comments by November 26, 2001. 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 
regulatory agencies on February 7, 2002.
    This guidance is an annex to an ICH guidance entitled ``Q1A(R) 
Stability Testing of New Drug Substances and Products'' (66 FR 56332). 
It is intended to provide guidance on the application of bracketing and 
matrixing for stability studies conducted in accordance with the 
principles outlined in Q1A(R).
    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 ICH Q1D 
guidance is intended to provide guidance on bracketing and matrixing 
designs. Specific principles are defined in this guidance for 
situations in which bracketing or matrixing can be applied and where 
bracketing or matrixing can be applied if additional justification is 
provided. Design factors and other considerations are presented, and 
potential risks of using reduced designs are discussed. Sample designs 
are also provided for illustrative purposes.
    This 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 statues and 
regulations.

II. Comments

    Interested persons may, at any time, submit to the Dockets 
Management Branch (see ADDRESSES) written comments on the guidance. 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 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, http://www.fda.gov/cber/publications.htm, or http://www.fda.gov/ohrms/dockets/default.htm.

    Dated: January 8, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-904 Filed 1-15-03; 8:45 am]
BILLING CODE 4160-01-S