International Conference on Harmonisation; Draft Guidance on Q1E Evaluation of Stability Data; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

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The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled “Q1E Evaluation of Stability Data.” The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use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 This draft guidance is an annex to an ICH guidance entitled “Q1A(R) Stability Testing of New Drug Substances and Products.” The draft guidance is intended to provide guidance on how to use stability data, generated in accordance with the principles outlined in Q1A(R), to propose a retest period for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Submit written or electronic comments on the draft guidance by August 1, 2002.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Submit written comments on the draft guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.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 Submit written requests for single copies of the draft guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857;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 See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.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 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.