International Conference on Harmonisation; M4 Common Technical Document; Request for Comments on Initial Components; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice; request for comments.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of initial components of a draft guidance entitled “M4 Common Technical Document,” which is being developed under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Because of the large size of the draft guidance, FDA is making some components of the draft guidance available to the public at this time to help explain the overall scheme of the draft guidance and to request comments. When completed, the guidance entitled “M4 Common Technical Document” will describe a harmonized format and content for designated new product applications for submission to the regulatory authorities in the three ICH regions. The agency intends to make the entire draft guidance available to the public for comment once all the components have been drafted.

DATES:

Submit written comments on the initial components of the draft guidance by March 13, 2000.

ADDRESSES:

Submit written comments on these components of the draft guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. An electronic version of the components is available on the Internet at http://www.fda.gov/cder/guidance/index.htm or at http://www.fda.gov/cber/publications.htm.

FOR FURTHER INFORMATION CONTACT:

For the safety components: Joseph J. DeGeorge, Center for Drug Evaluation and Research (HFD-24), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-5476.

For the quality components: Charles P. Hoiberg, Center for Drug Evaluation and Research (HFD-810), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-2570, and Neil D. Goldman, Center for Biologics Evaluation and Research (HFM-20), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0377.

For the efficacy sections: Robert J. DeLap, Center for Drug Evaluation and Research (HFD-105), Food and Drug Administration, 9201 Corporate Blvd., Rockville, MD 20850, 301-827-2250.

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 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 medical product development among regulatory agencies.

ICH was organized to provide an opportunity for harmonization initiatives to be developed with input from both regulatory and industry representatives. ICH is concerned with harmonization 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 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 Therapeutics Products Programme, and the European Free Trade Area.

The ICH process has achieved significant harmonization of the technical requirements for the approval of pharmaceuticals for human use in the three ICH regions. However, until recently, the application documents in the three ICH regions had not been examined, and there are significantly different requirements in each region for the composition and organization of product applications. As a result, three Expert Working Groups for Quality, Safety, and Efficacy have been developing harmonized guidance for the content and format of common sections of an application, called the “common technical document.” Once finalized, the guidance entitled “M4 Common Technical Document” will describe an acceptable format and content for applications for human pharmaceuticals that, once supplemented with regional particulars, can be used with designated new products for submission to the regulatory authorities in the three ICH regions.

The ICH Steering Committee is overseeing the work on the common technical document through the use of milestones that reflect the stages of completion as work proceeds. A key goal is to ensure that the process for developing the common technical document is transparent. As part of this transparency, the ICH Steering Committee agreed, in October 1999, that the components of the draft guidance entitled “M4 Common Technical Document” be made available for public comment as they evolve. The components being made available by this notice are the product of the Quality, Safety, and Efficacy Expert Working Groups of the ICH. Received comments on these components will be considered by FDA and the appropriate expert working group as the draft guidance “M4 Common Technical Document” is finished. Once it is finalized, the guidance entitled “M4 Common Technical Document” will describe the format and content for a common technical document that, when supplemented by regional information, is suitable for submission to the regulatory authorities in the three ICH regions.

II. Organization of the Common Technical Document

The common technical document should be viewed as the common part of a submission for designated new products, presented in a modular fashion with summaries and tables. It is intended that one of the modules in the common technical document be reserved as a region-specific module.

The common technical document modular structure is envisioned as shown in the graphic at the end of this document and includes the following:

III. Components Being Made Available at This Time

In addition to the preamble to the draft guidance entitled “M4 Common Technical Document,” and an organizational graphic, the following components are being made available in the docket and on the Internet at this time:

1. Module IIA—Nonclinical Executive Summary;

2. Module IIB—Nonclinical Written and Tabulated Summaries;

3. Module III—Quality table of contents and explanatory notes (nine attachments still pending);

4. Module IV—Nonclinical Data Study Reports table of contents and explanatory notes; and

5. Module V—Clinical Data Study Reports table of contents and explanatory notes.

These components detail the tables of contents for Modules III, IV, and V accompanied by explanatory notes. Module III will be supplemented further by a series of nine detailed attachments, which may be available in summer of 2000. (The exact content of Module III may evolve as the Expert Working Group's discussions progress.) Modules IIA Clinical and Quality and IIC should also be available for consultation in summer 2000. Module IIA/B Nonclinical is being made available at this time.

The ICH Steering Committee and Expert Working Groups are requesting comments on the components being made available by this notice. Once all the components of the draft guidance entitled “M4 Common Technical Document” are ready, a compiled text will be released to complete step 2 of the ICH process. It is anticipated that this will occur in summer 2000.

These components of the draft guidance represent the agency's current thinking on the content and format of a common application for designated new products (i.e., the common technical document). These components do not create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.

IV. Comments

Interested persons may, on or before March 13, 2000, submit to the Dockets Management Branch (address above) written comments on these components of the draft 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 components of the draft guidance, made available by this notice, and received comments may be seen in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through Friday.