[Federal Register Volume 66, Number 200 (Tuesday, October 16, 2001)]
[Notices]
[Pages 52634-52637]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-25921]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-0186]


International Conference on Harmonisation; Guidance on M4 Common 
Technical Document; 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 guidance entitled ``M4 Organization of the Common 
Technical Document for the Registration of Pharmaceuticals for Human 
Use'' (M4 CTD). The guidance was developed under the auspices of the 
International Conference on Harmonisation of

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Technical Requirements for Registration of Pharmaceuticals for Human 
Use (ICH). The guidance, which is being made available simultaneously 
in four parts (general organization, quality, safety, and efficacy), 
describes a harmonized format for new product applications (including 
applications for biotechnology-derived products) for submission to the 
regulatory authorities in the three ICH regions. The M4 CTD 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 or electronic comments on agency guidances at any 
time.

ADDRESSES: Submit written requests for single copies of the 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), 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. Submit written comments 
on the 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. 
Requests and comments should be identified with the docket number found 
in brackets in the heading of this document. See the SUPPLEMENTARY 
INFORMATION section of this document for electronic access to the 
guidance.

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, or David Green, Center for Biologics Evaluation and 
Research (HFM-579), Food and Drug Administration, 1401 Rockville Pike, 
Rockville, MD 20852, 301-827-5349.
    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, or Neil Goldman, 
Center for Biologics Evaluation and Research (HFM-20), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0372.
    For the efficacy (clinical) sections: Robert Temple, Center for 
Drug Evaluation and Research (HFD-40), Food and Drug Administration, 
9201 Corporate Blvd., Rockville, MD 20850, 301-594-6758, or Lou 
Marzella, Center for Biologics Evaluation and Research (HFM-582), Food 
and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-
827-5080.
    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, when possible, 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, Labor, 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 format of 
the technical documentation in an application to market a new medicinal 
product in the three ICH regions had not been considered in the ICH 
process although there are substantial differences in the organization 
of product applications in different parts of the world. ICH, 
therefore, convened three Expert Working Groups (with expertise in 
quality, safety, and efficacy of human drug and therapeutic biological 
products) to develop harmonized guidance for the format of sections of 
a marketing application for a new medicinal product. This effort is 
called the ``common technical document.'' The resulting ICH guidance M4 
CTD describes an acceptable format for applications for new human 
pharmaceuticals that (supplemented with regional particulars) can be 
used for submission to the regulatory authorities in each of the three 
ICH regions. The organization and format guidance provided in the M4 
CTD is intended to be used together with information about the content 
of an application, which is provided in other ICH and FDA guidances.
    In the Federal Register of February 11, 2000 (65 FR 7024), the 
agency announced the availability of initial components of the draft 
CTD guidance and requested public comment. Comments from that 
announcement were considered in developing a draft tripartite guidance, 
which was made available in the Federal Register of August 24, 2000 (65 
FR 51621). The notice for the draft guidance gave interested persons an 
opportunity to submit comments by September 30, 2000.
    To facilitate the process of making ICH guidances available to the 
public, the agency has changed 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 of this document). 
Draft guidances are left in their original ICH format. Final guidances 
are reformatted and edited to

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conform to the good guidance practices (GGP) style before publication.
    After consideration of the comments received and revisions to the 
guidance, a final draft of the guidance was submitted to the ICH 
Steering Committee and endorsed by the three participating regulatory 
agencies in November 2000.
    In accordance with FDA's GGP regulation (21 CFR 10.115), ICH 
guidance documents are now being called guidances, rather than 
guidelines.

II. The Common Technical Document

    The M4 CTD guidance describes a harmonized format 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 guidance addresses the organization of information presented in 
new product applications. With appropriate modifications, the guidance 
can also be applied to abbreviated or other applications. The guidance 
is not intended to indicate what studies should be included, but 
indicates 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.
    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 1: Administrative Information and Prescribing Information
    1.1 Table of Contents of the Submission Including Module 1
    1.2 Documents Specific to Each Region (for example, application 
forms, prescribing                   information)
Module 2: Common Technical Document Summaries
    2.1 CTD Table of Contents
    2.2 CTD Introduction
    2.3 Quality Overall Summary
    2.4 Nonclinical Overview
    2.5 Clinical Overview
    2.6 Nonclinical Written and Tabulated Summaries
          Pharmacology
          Pharmacokinetics
          Toxicology
    2.7 Clinical Summary
          Biopharmaceutics and Associated Analytical Methods
          Clinical Pharmacology Studies
          Clinical Efficacy
          Clinical Safety
          Synopses of Individual Studies
Module 3: Quality
    3.1 Module 3 Table of Contents
    3.2 Body of Data
    3.3 Literature References
Module 4: Nonclinical Study Reports
    4.1 Module 4 Table of Contents
    4.2 Study Reports
    4.3 Literature References
Module 5: Clinical Study Reports
    5.1 Module 5 Table of Contents
    5.2 Tabular Listing of All Clinical Studies
    5.3 Clinical Study Reports
    5.4 Literature References

    The 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 CTD; (2) the Quality section; (3) the Safety, or 
nonclinical, section; and (4) the Efficacy, or clinical, section.
    It should be noted that, as part of the ICH process, additional 
guidance is being developed to facilitate the submission of CTD 
applications using standardized electronic (computer) formats. This 
``electronic CTD,'' or ``E-CTD,'' is an ultimate aim of current 
harmonization efforts in this area. There may be some modifications in 
the CTD format to facilitate the preparation and utility of the E-CTD, 
although substantive modifications are not anticipated.
    This guidance represents the agency's current thinking on the 
organization and format of a common application for new products (i.e., 
the common technical document). 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.

III. Comments

    Interested persons may, at any time, submit to the Dockets 
Management Branch (address above) written comments regarding the 
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 
guidance and received comments may be seen in the Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

IV. Electronic Access

    Copies of the guidance are available on the Internet 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.

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[GRAPHIC] [TIFF OMITTED] TN16OC01.000


    Dated: October 9, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-25921 Filed 10-15-01; 8:45 am]
BILLING CODE 4160-01-C