[Federal Register: August 24, 2000 (Volume 65, Number 165)]
[Notices]               
[Page 51621-51624]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr24au00-90]                         

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-0186]

 
International Conference on Harmonisation; Draft Guidance on M4 
Common Technical Document; 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availability of a draft guidance entitled ``M4 Organization of the 
Common Technical Document for the Registration of Pharmaceuticals for 
Human Use'' (M4 Common Technical Document). The draft guidance was 
developed under the auspices of the International Conference on 
Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH). The draft guidance, which is being 
made available simultaneously in four parts, describes a harmonized 
format and content for new product applications (including applications 
for biotechnology-derived products) for submission to the regulatory 
authorities in the three ICH regions. The M4 Common Technical Document 
is intended to reduce the time and resources used to compile 
applications, ease the preparation of electronic submissions, 
facilitate regulatory reviews and communication with the applicant, and 
simplify the exchange of regulatory information among regulatory 
authorities.

DATES: Submit written comments on the draft guidance by September 30, 
2000.

ADDRESSES: Submit written comments on the draft guidance to the Dockets 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. Copies of the draft guidance are 
available on the Internet at http://www.fda.gov/cder/guidance/index.htm 
or at http://www.fda.gov/cber/publications.htm. Submit written requests 
for single copies of the draft guidance to the Drug Information Branch 
(HFD-210), Center for Drug Evaluation and Research, Food and Drug 
Administration, 5600 Fishers

[[Page 51622]]

Lane, Rockville, MD 20857; or the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and 
Research (CBER), 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.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: For the safety (nonclinical) 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 (clinical) 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 International 
Programs (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.
    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 
different requirements in the regions 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 ``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 new products for submission to the regulatory authorities 
in the three ICH regions. In the Federal Register of February 11, 2000 
(65 FR 7024), the agency announced the availability of initial 
components of the draft guidance and requested public comment. Comments 
from that announcement were considered in developing this draft 
guidance.
    In July 2000, the ICH Steering Committee agreed that a draft 
guidance entitled ``M4 Common Technical Document'' should be made 
available for public comment. Comments about the draft guidance will be 
considered by FDA and the appropriate expert working group.
    To facilitate the process of making ICH guidances available to the 
public, the agency is changing its procedures for publishing ICH 
guidances. Since 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 the ADDRESSES section). The draft guidance 
is left in the original ICH format. The final guidance will be 
reformatted to conform to the GGP style before publication.
    In accordance with FDA's good guidance practices (GGP) (62 FR 8961, 
February 27, 1997), ICH guidance documents are now being called 
guidances, rather than guidelines.

II. The Common Technical Document

    The draft guidance describes a harmonized format and content for 
new product applications (including applications for biotechnology-
derived products) for submission to the regulatory authorities in the 
three ICH regions. The common technical document is intended to reduce 
the time and resources used to compile applications, ease the 
preparation of electronic submissions, facilitate regulatory reviews 
and communication with the applicant, and simplify the exchange of 
regulatory information among regulatory authorities.
    The draft guidance addresses the organization of information 
presented in new product applications. With appropriate modifications, 
the draft guidance may be applied to abbreviated or other applications. 
The draft guidance is not intended to indicate what studies should be 
included, but merely to indicate an appropriate format for data that 
are submitted.
    The common technical document should be viewed as the common part 
of a submission for new products, presented in a modular fashion with 
summaries and tables. It is intended that one of the modules (module I) 
in the common technical document be reserved as a region-specific 
module, and thus will not be harmonized.
    When finalized, the common technical document modular structure is 
envisioned as shown in the graphic at the end of this notice and the 
following table of contents for the document:

Module I: Administrative Information and Prescribing Information 
Documents are region specific; for example, application forms, 
prescribing information.
Module II: Common Technical Document Summaries
    A. Overall Common Technical Document Table of Contents
    B. Overall Summaries
    1. Introduction
    2. Quality Overall Summary
    3. Nonclinical Overall Summary
    4. Clinical Overall Summary
    C. Nonclinical Summaries
    1. Pharmacology
    a. Written summary

[[Page 51623]]

    b. Tabulated summary
    2. Pharmacokinetics
    a. Written summary
    b. Tabulated summary
    3. Toxicology
    a. Written summary
    b. Tabulated summary
    D. Clinical Written Summary
    1. Biopharmaceutics and Associated Analytical Methods
    2. Clinical Pharmacology
    3. Clinical Efficacy
    4. Clinical Safety
    5. Synopses of Individual Studies
Module III: Quality
    A. Table of Contents
    B. Body of Data
Module IV: Nonclinical Study Reports
    A. Table of Contents
    B. Study Reports
    C. Key Literature References
Module V: Clinical Study Reports
    A. Table of Contents
    B. Study Reports
    C. Key Literature References

    The draft guidance being made available with this notice is the 
product of the ICH Common Technical Document Expert Working Groups for 
Quality, Safety, and Efficacy. To facilitate the handling of the 
guidance, it is being made available in four parts: (1) A description 
of the organization of the M4 Common Technical Document; (2) the 
Quality section; (3) the Safety, or nonclinical section; and (4) the 
Efficacy, or clinical section.
    This draft guidance represent the agency's current thinking on the 
content and format of a common application for new products (i.e., the 
common technical document). The draft guidance 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, regulations, or 
both.
    Interested persons may submit to the Dockets Management Branch 
(address above) written comments on the draft guidance by September 30, 
2000. 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 and received comments may be seen in 
the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through 
Friday.
BILLING CODE 4160-01-F
[GRAPHIC] [TIFF OMITTED] TN24AU00.000



[[Page 51624]]


    Dated: August 15, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-21563 Filed 8-23-00; 8:45 am]
BILLING CODE 4160-01-C