[Federal Register: September 13, 2004 (Volume 69, Number 176)]
[Notices]               
[Page 55163-55164]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr13se04-48]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0377]

 
International Conference on Harmonisation; Draft Guidance on E14 
Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic 
Potential for Non-Antiarrhythmic Drugs; 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availability of a draft guidance entitled ``E14 Clinical Evaluation of 
QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-
Antiarrhythmic Drugs.'' The draft guidance was prepared under the 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The draft guidance provides recommendations to sponsors concerning 
clinical studies to assess the potential of a new drug to cause cardiac 
arrhythmias, focusing on the assessment of changes in the QT/QTc 
interval on the electrocardiogram as a predictor of risk. The draft 
guidance is intended to encourage the assessment of drug effects on the 
QT/QTc interval as a standard part of drug development and to encourage 
the early discussion of this assessment with FDA.

DATES: Submit written or electronic comments on the draft guidance by 
December 13, 2004.

ADDRESSES: Submit written comments on the draft guidance to the 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. Submit written 

requests for single copies of the draft guidance to the Division of 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), 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-

[[Page 55164]]

1800. Send two self-addressed adhesive labels to assist the office in 
processing your requests. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Douglas C. Throckmorton, Center for Drug 
Evaluation and Research (HFD-1), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857.
    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

    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 drug development among regulatory agencies.
    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, 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, Health Canada, and the European Free Trade Area.
    In June 2004, the ICH Steering Committee agreed that a draft 
guidance entitled ``E14 Clinical Evaluation of QT/QTc Interval 
Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs'' 
should be made available for public comment. The draft guidance is the 
product of the Efficacy Expert Working Group of the ICH. Comments about 
this draft will be considered by FDA and the the Efficacy Expert 
Working Group.
    The draft guidance provides guidance on the design, conduct, 
analysis and interpretation of clinical studies to assess the potential 
of a new drug to cause cardiac arrhythmias, focusing on the assessment 
of changes in the QT/QTc interval on the electrocardiogram as a 
predictor of risk. The draft guidance is intended to encourage the 
assessment of drug effects on the QT/QTc interval, along with the 
collection of adverse cardiac events related to arrhythmias, as a 
standard part of drug development, and to encourage the early 
discussion of this assessment with the FDA. The goal of such 
discussions is to reach a common understanding of the effects as early 
in development as practical, with the goal of enhancing the efficiency 
of data collection later in drug development.
    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. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.


    Dated: September 3, 2004.
William K. Hubbard,
Associate Commissioner for Policy and Planning.
[FR Doc. 04-20565 Filed 9-10-04; 8:45 am]

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