
[Federal Register: August 28, 2008 (Volume 73, Number 168)]
[Notices]               
[Page 50825-50826]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28au08-77]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0449]

 
Draft Guidance for Industry on Integrated Summary of 
Effectiveness; 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availability of a draft guidance for industry entitled ``Integrated 
Summary of Effectiveness.'' This draft guidance describes how an 
integrated summary of effectiveness (ISE) should be prepared by 
industry for new drug applications (NDAs) and biologics license 
applications (BLAs). This guidance, when final, will supersede section 
G, Integrated Summary of Effectiveness Data, of the 1988 guidance on 
``Format and Content of the Clinical and Statistical Sections of an 
Application'' (Clin-Stat guidance). This guidance also incorporates the 
conceptual framework of section 2.7.3, Summary of Clinical Efficacy, 
from the International Conference on Harmonisation (ICH) guidance for 
industry ``M4E The CTD --Efficacy.'' This guidance is intended to 
improve the quality of product applications by describing what efficacy 
information should be submitted so that FDA can make a regulatory 
decision on an application.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit written or electronic comments on the draft guidance 
by October 27, 2008.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002; or 
the Office of Communication, Training, and Manufacturers Assistance 
(HFM-40), Center for Biologics Evaluation and Research, 1401 Rockville 
Pike, Rockville, MD 20852-1448. The guidance may also be obtained from 
the Center for Biologics Evaluation and Research by mail by calling 1-
800-835-4709 or 301-827-1800. See the SUPPLEMENTARY INFORMATION section 
for electronic access to the draft guidance document. Send one self-
addressed adhesive label to assist that office in processing your 
requests.

    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.regulations.gov.

FOR FURTHER INFORMATION CONTACT:
    Howard Chazin, Center for Drug Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 6470, 
Silver Spring, MD 20993-0002, 301-796-0700; or
    Leonard Wilson, Center for Biologics Evaluation and Research (HFM-
25), Food and Drug Administration, 1401 Rockville Pike, suite 576N, 
Rockville, MD 20852, 301-827-1053.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Integrated Summary of Effectiveness.'' This draft guidance 
describes how an ISE should be prepared by industry for NDAs and BLAs. 
The ISE has been required as part of an NDA submission (21 CFR 
314.50(d)(5)(v)) since 1985, but the regulation does not describe the 
specific components of the ISE. The Clin-Stat guidance provides a 
description of what FDA recommends be included in an ISE. However, 
since the Clin-Stat guidance was published, several International 
Conference on Harmonisation guidances, including the ICH guidances for 
industry ``E3 Structure and Content of Clinical Study Reports,'' ``E10 
Choice of Control Group and Related Issues in Clinical Trials,'' and 
``M4E The CTD--Efficacy,'' have provided further recommendations for 
describing individual trials and providing results of efficacy 
analyses. This guidance, when final, will supersede section G of the 
Clin-Stat guidance to reflect FDA's current thinking regarding the 
format and content of the ISE to provide a truly integrated analysis, 
rather than a summary of efficacy results from individual clinical 
trials, and to satisfy FDA regulatory requirements. Although there are 
no corresponding regulations requiring an ISE for BLA submissions, 
applicants are encouraged to provide these analyses.
    Regarding the common technical document, the ISE is often confused 
with the document included in Module 2, section 2.7.3, Summary of 
Clinical Efficacy. Although one of the goals of the ISE is to summarize 
the available effectiveness data, the ISE primarily is intended to be 
an integrated analysis of these data, going beyond a simple summary. 
The focus of the ISE is not on the detailed results of the individual 
studies, which are described in individual study reports, but a 
comprehensive, detailed, in-depth analysis that goes beyond individual 
study results to examine the basis for the entire approach taken.
    This draft guidance is being issued consistent with FDA's good 
guidance

[[Page 50826]]

practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the agency's current thinking on the content 
and format of the ISE. 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. The Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). 
The collections of information in 21 CFR part 314 have been approved 
under 0910-0001. The collections of information for submission of data 
in a BLA under 21 CFR 601.2 have been approved under 0910-0338.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
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. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.
    Please note that on January 15, 2008, the FDA Division of Dockets 
Management Web site transitioned to the Federal Dockets Management 
System (FDMS). FDMS is a Government-wide, electronic docket management 
system. Electronic comments or submissions will be accepted by FDA only 
through FDMS at http://www.regulations.gov.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/cber/
guidelines.htm or http://www.regulations.gov.

    Dated: August 19, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-19906 Filed 8-27-08; 8:45 am]

BILLING CODE 4160-01-S
