05-2418. International Conference on Harmonisation; Draft Guidance on S8 Immunotoxicity Studies for Human Pharmaceuticals; Availability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The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled “S8 Immunotoxicity Studies for Human Pharmaceuticals.” The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use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). The draft guidance describes a weight-of-evidence approach to determining whether additional immunotoxicity testing for nonbiological pharmaceuticals is appropriate when the findings from standard toxicity studies indicate signs of immunotoxicity. The draft guidance is intended to provide recommendations on nonclinical testing to identify compounds that have the potential to be immunosuppressive and guidance on a weight-of-evidence decision making approach for immunotoxicity testing.

DATES:

Submit written or electronic comments on the draft guidance by April 11, 2005. General comments on agency guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of the draft guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research (CDER), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD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. The guidance may also be obtained by mail by calling the CBER Voice Information System at 1-800-835-4709 or 301-827-1800. Send one self-addressed adhesive label to assist the office in processing your requests. Submit written comments on the draft guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.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 See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.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: Kenneth L. Hastings, Center for Drug Evaluation and Research (HFD-024), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-5922.

Regarding the ICH:

Michelle Limoli, Office of International Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4480.

SUPPLEMENTARY INFORMATION:

I. Background

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, CDER and CBER (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.

The ICH Steering Committee includes representatives from each of the ICH sponsors and the IFPMA, as well as observers from the World Health Organization (WHO), Health Canada, and the European Free Trade Area.

In November 2004, the ICH Steering Committee agreed that a draft guidance entitled “S8 Immunotoxicity Studies for Human Pharmaceuticals” should be made available for public comment. The draft guidance is the product of the Safety Expert Working Group of the ICH. Comments about this draft guidance will be considered by FDA and the Safety Expert Working Group.

The draft guidance describes a weight-of-evidence approach to determining whether additional immunotoxicity testing for nonbiological pharmaceuticals is appropriate when the findings from standard toxicity studies indicate signs of immunotoxicity. The draft guidance provides the following: (1) Recommendations on nonclinical testing approaches to identify compounds which have the potential to be immunosuppressive and (2) guidance on a weight-of-evidence decision making approach for immunotoxicity testing. The primary data are from routine nonclinical toxicology studies conducted during drug development. Additional causes for concern that can affect the decision for additional immunotoxicity testing include the pharmacology of the drug, intended patient population, known drug class effects, and retention of the drug in cells of the immune system.

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). This draft guidance, when finalized, will represent 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 Division of Dockets Management (see ADDRESSES) written or electronic comments on the draft guidance. Two copies of mailed 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 Division of Dockets Management 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: February 1, 2005.

Jeffrey Shuren,

Assistant Commissioner for Policy.