[Federal Register Volume 81, Number 216 (Tuesday, November 8, 2016)]
[Notices]
[Pages 78605-78606]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-26931]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-D-0075]


Non-Inferiority Clinical Trials To Establish Effectiveness; 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry entitled ``Non-Inferiority 
Clinical Trials to Establish Effectiveness.'' This document provides 
guidance to sponsors and applicants submitting investigational new drug 
applications (INDs), new drug applications (NDAs), biologics licensing 
applications (BLAs), or supplemental applications on the appropriate 
use of non-inferiority (NI) study designs to provide evidence of the 
effectiveness of a drug or biologic. The guidance gives advice on when 
NI studies demonstrating effectiveness of an investigational drug can 
provide interpretable results, how to choose the NI margin, and how to 
test the NI hypothesis.

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-2010-D-0075 for ``Non-Inferiority Clinical Trials to Establish 
Effectiveness; Guidance for Industry.'' 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, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. 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: Scott Goldie, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire

[[Page 78606]]

Ave., Bldg. 21, Rm. 3557, Silver Spring, MD 20993-0002, 301-796-2055; 
or Robert Temple, Center for Drug Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4212, 
Silver Spring, MD 20993-0002, 301-796-2270; 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 ``Non-Inferiority Clinical Trials to Establish 
Effectiveness.'' This guidance consists of four parts. The first part 
is a general discussion of regulatory, study design, scientific, and 
statistical issues associated with the use of NI studies to establish 
the effectiveness of a drug or biologic. The second part focuses on 
some of these issues in more detail, notably the statistical approaches 
used to determine the NI margin and to test for non-inferiority. The 
third part addresses commonly asked questions about NI studies. The 
fourth part includes four examples of successful and unsuccessful 
efforts to define NI margins and test for non-inferiority.
    This guidance finalizes the draft guidance for industry, ``Non-
Inferiority Clinical Trials,'' published in 2010. In addition, it 
supersedes the guidance for industry, ``Antibacterial Drug Products: 
Use of Noninferiority Trials to Support Approval,'' also published in 
2010, which will be withdrawn.
    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 NI clinical trials to establish 
effectiveness. 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. 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: November 3, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-26931 Filed 11-7-16; 8:45 am]
 BILLING CODE 4164-01-P