[Federal Register Volume 67, Number 115 (Friday, June 14, 2002)]
[Notices]
[Pages 40949-40950]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-15001]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 02D-0237]


International Conference on Harmonisation; Draft Guidance on Q1E 
Evaluation of Stability Data; 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availability of a draft guidance entitled ``Q1E Evaluation of Stability 
Data.'' The draft guidance was prepared under the auspices of the 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 This draft 
guidance is an annex to an ICH guidance entitled ``Q1A(R) Stability 
Testing of New Drug Substances and Products.'' The draft guidance is 
intended to provide guidance on how to use stability data, generated in 
accordance with the principles outlined in Q1A(R), to propose a retest 
period for the drug substance and a shelf life for the drug product.

DATES: Submit written or electronic comments on the draft guidance by 
August 1, 2002.

ADDRESSES: Submit written comments on the draft guidance to the Dockets 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. Submit written requests for 
single copies of the draft guidance to the Division of Drug Information 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INFORMATION section for electronic access to the draft guidance 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, Rockville, MD 20852-1148, 301-402-
4635.
Regarding the ICH: Janet J. 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 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

[[Page 40950]]

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. Beginning 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 will be 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 February 2002, the ICH Steering Committee agreed that a draft 
guidance entitled ``Q1E Evaluation of Stability Data'' 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.
    This draft 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). The draft guidance is intended to provide 
guidance on how to use stability data, generated in accordance with the 
principles outlined in Q1A(R), to propose a retest period for the drug 
substance and a shelf life for the drug product.
    The guidance on the evaluation and statistical analysis of 
stability data provided in Q1A(R) is brief in nature and limited in 
scope. Although Q1A(R) states that regression analysis is an acceptable 
approach to analyzing quantitative stability data for retest period or 
shelf life estimation and recommends that a statistical test for batch 
poolability be performed using a level of significance of 0.25, it 
includes few details on these topics. In addition, Q1A(R) does not 
cover situations where multiple factors are involved in a full- or 
reduced-design study. This draft guidance provides a clear explanation 
of expectations when proposing a retest period or shelf life and 
storage conditions based on the evaluation of stability data for both 
quantitative and qualitative test attributes. It outlines 
recommendations for establishing a retest period or shelf life based on 
stability data from single-factor or multifactor and full- or reduced-
design studies. The draft guidance further describes when and how 
limited extrapolation can be undertaken to propose a retest period or 
shelf life beyond the observed range of data from the long-term storage 
condition. When finalized, the Q1E guidance will supersede the 
``Evaluation'' sections of Q1A(R).
    This draft guidance, when finalized, will represent the agency's 
current thinking on stability data evaluation. 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 (see 
ADDRESSES) written comments on the draft guidance by August 1, 2002. 
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 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 may obtain the document at 
http://www.fda.gov/ohrms/dockets/default.htm, http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.

    Dated: June 6, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-15001 Filed 6-13-02; 8:45 am]
BILLING CODE 4160-01-S