[Federal Register Volume 70, Number 202 (Thursday, October 20, 2005)]
[Notices]
[Pages 61134-61135]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-20971]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0377]


International Conference on Harmonisation; 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 guidance entitled ``E14 Clinical Evaluation of QT/QTc 
Interval Prolongation and Proarrhythmic Potential for Non-
Antiarrhythmic Drugs.'' The guidance was prepared under the auspices of 
the International Conference on Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use (ICH). The 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 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 agency guidances at any 
time.

ADDRESSES: Submit written comments on the 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://www.fda.gov/dockets/ecomments. 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), 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 301-827-1800. Send one self-
addressed adhesive label to assist the office in processing your 
request. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the 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, 301-594-5400.
    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

[[Page 61135]]

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 the Federal Register of September 13, 2004 (69 FR 55163), FDA 
published a notice announcing the availability of a draft tripartite 
guidance entitled ``E14 Clinical Evaluation of QT/QTc Interval 
Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic 
Drugs.'' The notice gave interested persons an opportunity to submit 
comments by December 13, 2004. In response to a request for additional 
time to comment, FDA reopened the comment period until February 18, 
2005 (70 FR 823, January 5, 2005). On April 11 and 12, 2005, FDA, the 
Drug Information Association, and the Heart Rhythm Society cosponsored 
a public meeting to discuss the draft guidance. Comments received at 
the meeting were made available to the Efficacy Expert Working Group. 
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 May 2005.
    The 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 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. The guidance incorporates the following changes: (1) A 
fuller discussion of the factors that influence the clinical assessment 
of drug effects on the QT interval and (2) an adjustment in the 
statistical analysis of QT interval data obtained as a part of early 
thorough QT assessment.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents 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 guidance at 
anytime. 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 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://www.fda.gov/ohrms/dockets/default.htm, http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.

    Dated: October 12, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-20971 Filed 10-19-05; 8:45 am]
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