61134 Federal Register / Vol. 70, No. 202 / Thursday, October 20, 2005 / Notices 

In the Federal Register of September 

13, 2004 (69 FR 55163), FDA published 

a notice announcing the availability of 

a draft tripartite guidance entitled ‘‘S7B 

Nonclinical Evaluation of the Potential 

for Delayed Ventricular Repolarization 

(QT Interval Prolongation) by Human 

Pharmaceuticals.’’ 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). 

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 

nonclinical assessment of the effects of 

pharmaceuticals on ventricular 

repolarization and proarrhythmic risk. 

The guidance describes a nonclinical 

testing strategy for assessing the 

potential of a test substance to delay 

ventricular repolarization and includes 

information concerning nonclinical 

assays and an integrated risk 

assessment. 

This 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 any time. 

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 

above 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, 

Assisstant Commissioner for Policy. 

[FR Doc. 05–20959 Filed 10–19–05; 8:45 am] 

BILLING CODE 4160–01–S 

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. 

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 

Federal Register / Vol. 70, No. 202 / Thursday, October 20, 2005 / Notices 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] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2005D–0362] 

Draft Guidance for Industry on 

Recommendations for Implementing a 

Collection Program for Source Plasma 

Containing Disease-Associated and 

Other Immunoglobulin Antibodies; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft document entitled 

‘‘Guidance for Industry: 

Recommendations for Implementing a 

Collection Program for Source Plasma 

Containing Disease-Associated and 

Other Immunoglobulin (IgG) 

Antibodies,’’ dated October 2005. The 

draft guidance document is intended to 

assist source plasma manufacturers in 

submitting to FDA the appropriate 

information when implementing an IgG 

antibody collection program or when 

adding a new IgG antibody collection to 

an existing program. The draft guidance, 

when finalized, would supersede the 

draft reviewers’ guide entitled ‘‘Disease 

Associated Antibody Collection 

Program,’’ dated October 1, 1995. 

DATES: Submit written or electronic 

comments on the draft guidance by 

January 18, 2006 to ensure their 

adequate consideration in preparation of 

the final guidance. General comments 

on agency guidance documents are 

welcome at any time. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance to 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. Send one 

self-addressed adhesive label to assist 

the office in processing your requests. 

The draft guidance may also be obtained 

by mail by calling CBER at 1–800–835–

4709 or 301–827–1800. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the draft guidance 

document. 

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:// 

www.fda.gov/dockets/ecomments. 

FOR FURTHER INFORMATION CONTACT: 

Brenda R. Friend, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, 1401 

Rockville Pike, suite 200N, Rockville, 

MD 20852–1448, 301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft document entitled ‘‘Guidance for 

Industry: Recommendations for 

Implementing a Collection Program for 

Source Plasma Containing DiseaseAssociated and Other Immunoglobulin 

(IgG) Antibodies’’ dated October 2005. 

The draft guidance, when finalized, 

would supersede the draft reviewers’

guide, ‘‘Disease Associated Antibody 

Collection Program,’’ dated October 1, 

1995. The document provides guidance 

to source plasma manufacturers in 

submitting the appropriate information 

to FDA when implementing an IgG 

antibody collection program or when 

adding a new IgG antibody collection to 

an existing program. The guidance 

identifies changes in collection 

programs that must be documented as 

minor changes in an annual report to 

FDA under § 601.12(d) (21 CFR 

601.12(d)). These collection programs 

include disease-associated IgG