[Federal Register Volume 74, Number 75 (Tuesday, April 21, 2009)]
[Notices]
[Page 18241]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-9051]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2007-D-0031] (formerly Docket No. 2007D-0233)


Guidance for Industry on Integrated Summaries of Effectiveness 
and Safety: Location Within the 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 a guidance for industry entitled ``Integrated Summaries 
of Effectiveness and Safety: Location Within the Common Technical 
Document.'' Since FDA began accepting new drug application (NDA) and 
biologics license application (BLA) submissions in the common technical 
document (CTD) format, there has been confusion regarding where within 
the CTD to include an integrated summary of effectiveness (ISE) and 
integrated summary of safety (ISS), both of which are required 
components of an NDA submission and recommended components of a BLA 
submission. This guidance informs applicants where to place the ISE and 
ISS in the CTD, addresses specific FDA requirements not discussed in 
the ICH guidance for industry ``M4E: The CTD--Efficacy,'' and is 
intended to improve application quality and consistency. This guidance 
finalizes the draft guidance of the same title published in the Federal 
Register of July 3, 2007 (72 FR 36471).

DATES:  Submit written or electronic comments on agency guidances at 
any time.

ADDRESSES:  Submit written requests for single copies of this 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, Outreach and Development (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 CBER at 1-800-835-4709 or 301-827-1800. 
Send one self-addressed adhesive label to assist that office in 
processing your requests. 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.regulations.gov. See the 
SUPPLEMENTARY INFORMATION section for electronic access to the guidance 
document.

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 Stephen Ripley, Center for Biologics Evaluation and 
Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, 
suite 200N, Rockville, MD 20852, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Integrated Summaries of Effectiveness and Safety: Location 
Within the Common Technical Document.'' This guidance is intended for 
applicants submitting an NDA or BLA in the CTD or electronic common 
technical document (eCTD) format. Since FDA adopted the CTD, a standard 
way to organize a marketing or licensing application, there has been 
confusion regarding where to place an ISE and ISS within the CTD. The 
ISE and ISS are unique requirements of the United States and are not 
addressed fully by ICH M4E.
    FDA considers the ISE and ISS critical components of the clinical 
efficacy and safety portions of a marketing or licensing application. 
Therefore, the ISE and ISS are required in NDA applications submitted 
to FDA in accordance with the regulations in 21 CFR 314.50(d)(5)(v) and 
(d)(5)(vi)(a). Although there are no corresponding regulations 
requiring an ISE or ISS for BLAs, applicants are encouraged to provide 
these analyses.
    A common problem with the way many of the CTD-formatted 
applications are submitted is that applicants incorrectly assume that 
the clinical summaries in Module 2 satisfy the regulatory requirements 
for the ISE and ISS. This assumption can result in a determination by 
FDA that an application is incomplete. Despite their names, the ISE and 
ISS are detailed integrated analyses of all relevant data from the 
clinical study reports, not summaries. This guidance focuses on where 
to place ISE and ISS documents within the structure of the CTD or eCTD.
    This guidance updates the part of sections II.G. and H. of the 
guidance on the ``Format and Content of the Clinical and Statistical 
Sections of an Application'' that relates to placement of the ISE and 
ISS. This guidance finalizes the draft guidance of the same title that 
published in the Federal Register of July 3, 2007 (72 FR 36471). No 
public comments were received regarding the draft guidance.
    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 the location for an ISE and ISS within the 
CTD. 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 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.

III. Electronic Access

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

    Dated: April 10, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-9051 Filed 4-20-09; 8:45 am]
BILLING CODE 4160-01-S