[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