
[Federal Register Volume 81, Number 94 (Monday, May 16, 2016)]
[Notices]
[Pages 30310-30311]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-11438]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0872]


Considerations for Use of Histopathology and Its Associated 
Methodologies To Support Biomarker Qualification; 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) is announcing the 
availability of a guidance for industry entitled ``Considerations for 
Use of Histopathology and Its Associated Methodologies to Support 
Biomarker Qualification.'' This guidance is intended to assist 
submitters of a biomarker for qualification that conduct nonclinical 
biomarker qualification studies in which histopathology is used as a 
reference or truth standard. This guidance discusses the processes that 
we recommend be considered when generating histopathology data to be 
included in biomarker studies and outlines the scientific standards 
recommended for histopathology used in nonclinical biomarker 
characterization and qualification. The recommendations in this 
guidance are intended for confirmatory studies in nonclinical biomarker 
qualification that justify the proposed context of use, where 
scientifically rigorous evaluation of biomarker performance in relation 
to histopathologic changes is essential. The principles outlined in 
this guidance are also applicable to exploratory nonclinical biomarker 
studies. This guidance finalizes the draft guidance ``Use of Histology 
in Biomarker Qualification Studies,'' issued in December 2011.

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-2011-D-0872 for ``Considerations for Use of Histopathology and Its 
Associated Methodologies to Support Biomarker Qualification; 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. Send one self-
addressed adhesive label to assist that office in processing

[[Page 30311]]

your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Elizabeth Hausner, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 4145, Silver Spring, MD 20993-0002, 301-
796-1084.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Considerations for Use of Histopathology and Its Associated 
Methodologies to Support Biomarker Qualification.'' The FDA Critical 
Path Initiative identified the discovery, characterization, 
qualification, and use of biomarkers as important for improving the 
efficiency and success rate of medical product development. Biomarkers 
have been broadly applied to describe the following:
     Structural features from the molecular to the anatomic 
level (e.g., genetic composition, receptor expression patterns, 
radiographic appearances);
     Biochemical measurements (e.g., serum levels of 
electrolytes, cardiac troponins); and
     Physiologic organ system function tests (e.g., creatinine 
clearance, pulmonary function tests, cardiac ejection fraction, 
electrocardiography).
    The type of study reports to be submitted in support of a biomarker 
qualification will depend upon the proposed context of use and the 
ultimate goal of the submission. The proposed context of use dictates 
the depth, extent, and rigor of the supporting data for the biomarker. 
If a biomarker becomes qualified, analytically valid measurements of it 
can be relied upon to have a specific and interpretable meaning (e.g., 
physiologic, toxicologic, pharmacologic, or clinical) in drug 
development and regulatory decision-making. Industry can then employ 
the biomarker for the qualified context of use during premarketing drug 
development, and FDA reviewers can be confident about its qualified 
context of use without the need to reconfirm its applicability or 
utility. Accordingly, data supporting qualification of a nonclinical 
biomarker should be reliable, repeatable, and of assured integrity.
    In the Federal Register of December 30, 2011 (76 FR 82306), FDA 
announced the availability of a draft guidance entitled ``Use of 
Histology in Biomarker Qualification Studies.'' The Agency received 
several comments from the pharmaceutical industry and others. We have 
carefully considered the comments and have made the following changes 
in response to the comments: (1) Changed the title of the guidance to 
``Considerations for Use of Histopathology and Its Associated 
Methodologies to Support Biomarker Qualification''; (2) clarified the 
scope of the guidance; (3) added more information concerning data used 
to support biomarker qualification; (4) confirmed and clarified the 
rationale for assessment of outcomes without knowledge of group 
assignments in confirmatory studies; and (5) clarified the distinction 
between biomarker sensitivity and specificity. In addition we have made 
editorial changes to improve clarity. This guidance finalizes the draft 
guidance issued in December 2011.
    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 considerations for the use of histopathology 
and its associated methodologies to support biomarker qualification. 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. Paperwork Reduction Act of 1995

    This guidance contains information collection provisions 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 this guidance were approved under OMB 
control numbers 0910-0001 for submissions related to 21 CFR 314, and 
0910-0014 for submissions related to 21 CFR 312.

III. Electronic Access

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

    Dated: May 10, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-11438 Filed 5-13-16; 8:45 am]
 BILLING CODE 4164-01-P


