80_FR_61111 80 FR 60916 - Integrated Summary of Effectiveness; Guidance for Industry; Availability

80 FR 60916 - Integrated Summary of Effectiveness; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 195 (October 8, 2015)

Page Range60916-60917
FR Document2015-25630

The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled ``Integrated Summary of Effectiveness.'' This 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 is intended to improve the quality of drug applications by describing what efficacy information should be submitted so that FDA can make a regulatory decision on an application. This guidance finalizes the draft guidance issued August 28, 2008.

Federal Register, Volume 80 Issue 195 (Thursday, October 8, 2015) 
[Federal Register Volume 80, Number 195 (Thursday, October 8, 2015)]
[Notices]
[Pages 60916-60917]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-25630]



[[Page 60916]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Integrated Summary of Effectiveness; Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry entitled ``Integrated 
Summary of Effectiveness.'' This 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 is intended to improve the quality of drug applications 
by describing what efficacy information should be submitted so that FDA 
can make a regulatory decision on an application. This guidance 
finalizes the draft guidance issued August 28, 2008.

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

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2008-D-0449 for Integrated Summary of Effectiveness; Guidance for 
Industry; Availability. Received comments will be placed in the docket 
and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at http://www.regulations.gov or at the Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    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, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002; or the Office of 
Communication, Training, and Manufacturers Assistance, Center for 
Biologics Evaluation and Research, 10903 New Hampshire Ave., Bldg. 71, 
Rm. 3128, Silver Spring, MD 20993-0002. The guidance may also be 
obtained from the Center for Biologics Evaluation and Research by mail 
by calling 1-800-835-4709 or 240-402-7800. Send one self-addressed 
adhesive label to assist that office in processing your requests. See 
the SUPPLEMENTARY INFORMATION section for electronic access to the 
guidance document.

FOR FURTHER INFORMATION CONTACT: Helen Sile, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 6462, Silver Spring, MD 20993-0002, 301-796-4123; or 
Stephen Ripley, Center for Biologics Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, 
Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Integrated Summary of Effectiveness.'' This 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 since 1985 (21 
CFR 314.50(d)(5)(v)), but the regulation does not describe the specific 
components of the ISE. The guidance for industry ``Guideline for the 
Format and Content of the Clinical and Statistical Sections of an 
Application'' (Clin-Stat guidance) provides a description of what FDA 
recommends for inclusion 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

[[Page 60917]]

provided additional recommendations for describing individual trials 
and providing results of efficacy analyses.
    This guidance supersedes section II.G., Integrated Summary of 
Effectiveness Data, 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. 
This guidance also incorporates the conceptual framework of section 
2.7.3, Summary of Clinical Efficacy, from ICH M4E. Although there are 
no corresponding regulations requiring an ISE for BLA submissions, 
applicants are encouraged to provide these analyses.
    The focus of the ISE is not on the detailed results of individual 
studies, which are described in individual study reports, but a 
comprehensive, detailed, integrated analysis that goes beyond 
individual study results to examine all sources of information 
concerning effectiveness to provide further insight into the efficacy 
of the study drug. Integrated analyses included in an ISE generally 
fall into two broad categories: (1) Comparing the individual studies to 
better understand the overall results; and (2) using the greater power 
of pooled analyses to gain insight into the nature of the drug's 
effectiveness in demographic (e.g., age, sex, race, and ethnicity) and 
other subpopulations, dose-response, and onset and duration of effect, 
among others.
    A draft of this guidance was published for comment in the Federal 
Register on August 28, 2008 (73 FR 50825). Comments received on the 
draft guidance have been considered and the guidance has been revised 
as follows: (1) Clarification on the difference between the document 
included in Module 2, section 2.7.3, Summary of Clinical Efficacy, from 
ICH M4E, and the ISE has been provided; (2) the definition of 
integrated analyses has been revised and the components that constitute 
an integrated analyses have been clarified; (3) pooled analyses has 
been defined; and (4) the recommendations for when it is appropriate to 
pool data has been included.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on preparing an ISE. It does not establish any 
rights for any person and is not binding on FDA or the public. You can 
use an alternative approach if it 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 (OMB) 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 OMB control number 0910-0001. The collections of 
information for submission of data in a BLA under 21 CFR 601.2 have 
been approved under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the Internet may obtain the guidance at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.regulations.gov.

    Dated: October 2, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-25630 Filed 10-7-15; 8:45 am]
 BILLING CODE 4164-01-P

60916 Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Notices DEPARTMENT OF HEALTH AND Written/Paper Submissions received, go to http:// HUMAN SERVICES Submit written/paper submissions as www.regulations.gov and insert the follows: docket number, found in brackets in the Food and Drug Administration • Mail/Hand delivery/Courier (for heading of this document, into the written/paper submissions): Division of ‘‘Search’’ box and follow the prompts [Docket No. FDA–2008–D–0449] Dockets Management (HFA–305), Food and/or go to the Division of Dockets and Drug Administration, 5630 Fishers Management, 5630 Fishers Lane, Rm. Integrated Summary of Effectiveness; Lane, Rm. 1061, Rockville, MD 20852. 1061, Rockville, MD 20852. Guidance for Industry; Availability • For written/paper comments Submit written requests for single submitted to the Division of Dockets copies of this guidance to the Division AGENCY: Food and Drug Administration, of Drug Information, Center for Drug HHS. Management, FDA will post your comment, as well as any attachments, Evaluation and Research, Food and ACTION: Notice. except for information submitted, Drug Administration, 10001 New marked and identified, as confidential, Hampshire Ave., Hillandale Building, SUMMARY: The Food and Drug 4th Floor, Silver Spring, MD 20993– Administration (FDA or Agency) is if submitted as detailed in ‘‘Instructions.’’ 0002; or the Office of Communication, announcing the availability of a Training, and Manufacturers Assistance, guidance for industry entitled Instructions: All submissions received must include the Docket No. FDA– Center for Biologics Evaluation and ‘‘Integrated Summary of Effectiveness.’’ Research, 10903 New Hampshire Ave., This guidance describes how an 2008–D–0449 for Integrated Summary of Effectiveness; Guidance for Industry; Bldg. 71, Rm. 3128, Silver Spring, MD integrated summary of effectiveness 20993–0002. The guidance may also be (ISE) should be prepared by industry for Availability. Received comments will be placed in the docket and, except for obtained from the Center for Biologics new drug applications (NDAs) and Evaluation and Research by mail by biologics license applications (BLAs). those submitted as ‘‘Confidential Submissions,’’ publicly viewable at calling 1–800–835–4709 or 240–402– This guidance is intended to improve 7800. Send one self-addressed adhesive the quality of drug applications by http://www.regulations.gov or at the Division of Dockets Management label to assist that office in processing describing what efficacy information your requests. See the SUPPLEMENTARY should be submitted so that FDA can between 9 a.m. and 4 p.m., Monday through Friday. INFORMATION section for electronic make a regulatory decision on an access to the guidance document. application. This guidance finalizes the • Confidential Submissions—To submit a comment with confidential FOR FURTHER INFORMATION CONTACT: draft guidance issued August 28, 2008. information that you do not wish to be Helen Sile, Center for Drug Evaluation DATES: Submit either electronic or made publicly available, submit your and Research, Food and Drug written comments on Agency guidances comments only as a written/paper Administration, 10903 New Hampshire at any time. submission. You should submit two Ave., Bldg. 22, Rm. 6462, Silver Spring, ADDRESSES: You may submit comments copies total. One copy will include the MD 20993–0002, 301–796–4123; or as follows: information you claim to be confidential Stephen Ripley, Center for Biologics with a heading or cover note that states Evaluation and Research, Food and Electronic Submissions ‘‘THIS DOCUMENT CONTAINS Drug Administration, 10903 New Submit electronic comments in the CONFIDENTIAL INFORMATION.’’ The Hampshire Ave., Bldg. 71, Rm. 7301, following way: Agency will review this copy, including Silver Spring, MD 20993–0002, 240– • Federal eRulemaking Portal: http:// the claimed confidential information, in 402–7911. www.regulations.gov. Follow the its consideration of comments. The SUPPLEMENTARY INFORMATION: instructions for submitting comments. second copy, which will have the Comments submitted electronically, claimed confidential information I. Background including attachments, to http:// redacted/blacked out, will be available FDA is announcing the availability of www.regulations.gov will be posted to for public viewing and posted on a guidance for industry entitled the docket unchanged. Because your http://www.regulations.gov. Submit ‘‘Integrated Summary of Effectiveness.’’ comment will be made public, you are both copies to the Division of Dockets This guidance describes how an ISE solely responsible for ensuring that your Management. If you do not wish your should be prepared by industry for comment does not include any name and contact information to be NDAs and BLAs. The ISE has been confidential information that you or a made publicly available, you can required as part of an NDA submission third party may not wish to be posted, provide this information on the cover since 1985 (21 CFR 314.50(d)(5)(v)), but such as medical information, your or sheet and not in the body of your the regulation does not describe the anyone else’s Social Security number, or comments and you must identify this specific components of the ISE. The confidential business information, such information as ‘‘confidential.’’ Any guidance for industry ‘‘Guideline for the as a manufacturing process. Please note information marked as ‘‘confidential’’ Format and Content of the Clinical and that if you include your name, contact will not be disclosed except in Statistical Sections of an Application’’ information, or other information that accordance with 21 CFR 10.20 and other (Clin-Stat guidance) provides a identifies you in the body of your applicable disclosure law. For more description of what FDA recommends comments, that information will be information about FDA’s posting of for inclusion in an ISE. However, since mstockstill on DSK4VPTVN1PROD with NOTICES posted on http://www.regulations.gov. comments to public dockets, see 80 FR the Clin-Stat guidance was published, • If you want to submit a comment 56469, September 18, 2015, or access several International Conference on with confidential information that you the information at: http://www.fda.gov/ Harmonisation guidances, including the do not wish to be made available to the regulatoryinformation/dockets/ ICH guidances for industry ‘‘E3 public, submit the comment as a default.htm. Structure and Content of Clinical Study written/paper submission and in the Docket: For access to the docket to Reports,’’ ‘‘E10 Choice of Control Group manner detailed (see ‘‘Written/Paper read background documents or the and Related Issues in Clinical Trials,’’ Submissions’’ and ‘‘Instructions’’). electronic and written/paper comments and ‘‘M4E The CTD—Efficacy,’’ have VerDate Sep<11>2014 16:41 Oct 07, 2015 Jkt 238001 PO 00000 Frm 00045 Fmt 4703 Sfmt 4703 E:\FR\FM\08OCN1.SGM 08OCN1

Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Notices 60917 provided additional recommendations of the applicable statutes and ADDRESSES: You may submit comments for describing individual trials and regulations. as follows: providing results of efficacy analyses. II. The Paperwork Reduction Act of Electronic Submissions This guidance supersedes section 1995 II.G., Integrated Summary of Submit electronic comments in the Effectiveness Data, of the Clin-Stat This guidance refers to previously following way: guidance to reflect FDA’s current approved collections of information that • Federal eRulemaking Portal: http:// thinking regarding the format and are subject to review by the Office of www.regulations.gov. Follow the content of the ISE to provide a truly Management and Budget (OMB) under instructions for submitting comments. integrated analysis, rather than a the Paperwork Reduction Act of 1995 Comments submitted electronically, summary of efficacy results from (44 U.S.C. 3501–3520). The collections including attachments, to http:// individual clinical trials, and to satisfy of information in 21 CFR part 314 have www.regulations.gov will be posted to FDA regulatory requirements. This been approved under OMB control the docket unchanged. Because your guidance also incorporates the number 0910–0001. The collections of comment will be made public, you are conceptual framework of section 2.7.3, information for submission of data in a solely responsible for ensuring that your Summary of Clinical Efficacy, from ICH BLA under 21 CFR 601.2 have been comment does not include any M4E. Although there are no approved under OMB control number confidential information that you or a corresponding regulations requiring an 0910–0338. third party may not wish to be posted, ISE for BLA submissions, applicants are III. Electronic Access such as medical information, your or encouraged to provide these analyses. anyone else’s Social Security number, or Persons with access to the Internet confidential business information, such The focus of the ISE is not on the may obtain the guidance at http://www. detailed results of individual studies, as a manufacturing process. Please note fda.gov/Drugs/GuidanceCompliance that if you include your name, contact which are described in individual study RegulatoryInformation/Guidances/ reports, but a comprehensive, detailed, information, or other information that default.htm, http://www.fda.gov/ identifies you in the body of your integrated analysis that goes beyond BiologicsBloodVaccines/Guidance individual study results to examine all comments, that information will be ComplianceRegulatoryInformation/ posted on http://www.regulations.gov. sources of information concerning Guidances/default.htm, or http:// effectiveness to provide further insight • If you want to submit a comment www.regulations.gov. with confidential information that you into the efficacy of the study drug. Integrated analyses included in an ISE Dated: October 2, 2015. do not wish to be made available to the generally fall into two broad categories: Leslie Kux, public, submit the comment as a (1) Comparing the individual studies to Associate Commissioner for Policy. written/paper submission and in the better understand the overall results; [FR Doc. 2015–25630 Filed 10–7–15; 8:45 am] manner detailed (see ‘‘Written/Paper and (2) using the greater power of BILLING CODE 4164–01–P Submissions’’ and ‘‘Instructions’’). pooled analyses to gain insight into the Written/Paper Submissions nature of the drug’s effectiveness in Submit written/paper submissions as demographic (e.g., age, sex, race, and DEPARTMENT OF HEALTH AND HUMAN SERVICES follows: ethnicity) and other subpopulations, • Mail/Hand delivery/Courier (for dose-response, and onset and duration written/paper submissions): Division of Food and Drug Administration of effect, among others. Dockets Management (HFA–305), Food A draft of this guidance was [Docket No. FDA–2014–D–2138] and Drug Administration, 5630 Fishers published for comment in the Federal Lane, Rm. 1061, Rockville, MD 20852. Adverse Event Reporting for Register on August 28, 2008 (73 FR • For written/paper comments 50825). Comments received on the draft Outsourcing Facilities Under Section submitted to the Division of Dockets guidance have been considered and the 503B of the Federal Food, Drug, and Management, FDA will post your guidance has been revised as follows: Cosmetic Act; Guidance for Industry; comment, as well as any attachments, (1) Clarification on the difference Availability except for information submitted, between the document included in AGENCY: Food and Drug Administration, marked and identified, as confidential, Module 2, section 2.7.3, Summary of HHS. if submitted as detailed in Clinical Efficacy, from ICH M4E, and ACTION: Notice. ‘‘Instructions.’’ the ISE has been provided; (2) the Instructions: All submissions received definition of integrated analyses has SUMMARY: The Food and Drug must include the Docket No. FDA– been revised and the components that Administration (FDA or the Agency) is 2014–D–2138 for Adverse Event constitute an integrated analyses have announcing the availability of a final Reporting for Outsourcing Facilities been clarified; (3) pooled analyses has guidance for industry entitled ‘‘Adverse Under Section 503B of the Federal been defined; and (4) the Event Reporting for Outsourcing Food, Drug, and Cosmetic Act; recommendations for when it is Facilities Under Section 503B of the Guidance for Industry; Availability. appropriate to pool data has been Federal Food, Drug, and Cosmetic Act.’’ Received comments will be placed in included. Under the Federal Food, Drug, and the docket and, except for those This guidance is being issued Cosmetic Act (the FD&C Act), an submitted as ‘‘Confidential outsourcing facility must submit mstockstill on DSK4VPTVN1PROD with NOTICES consistent with FDA’s good guidance Submissions,’’ publicly viewable at practices regulation (21 CFR 10.115). adverse event reports to FDA. This http://www.regulations.gov or at the The guidance represents the current guidance explains FDA’s current Division of Dockets Management thinking of FDA on preparing an ISE. It thinking on adverse event reporting for between 9 a.m. and 4 p.m., Monday does not establish any rights for any these outsourcing facilities. through Friday. person and is not binding on FDA or the DATES: Submit either electronic or • Confidential Submissions—To public. You can use an alternative written comments on Agency guidances submit a comment with confidential approach if it satisfies the requirements at any time. information that you do not wish to be VerDate Sep<11>2014 16:41 Oct 07, 2015 Jkt 238001 PO 00000 Frm 00046 Fmt 4703 Sfmt 4703 E:\FR\FM\08OCN1.SGM 08OCN1


Document Created: 2015-12-15 08:42:45
Document Modified: 2015-12-15 08:42:45
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice.
DatesSubmit either electronic or written comments on Agency guidances at any time.
ContactHelen Sile, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6462, Silver Spring, MD 20993-0002, 301-796-4123; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.
FR Citation80 FR 60916 
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