
[Federal Register Volume 83, Number 238 (Wednesday, December 12, 2018)]
[Notices]
[Pages 63892-63894]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-26900]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-4267]


Biomarker Qualification: Evidentiary Framework; Draft Guidance 
for Industry and Food and Drug Administration Staff; 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the availability of a draft guidance for industry and FDA staff 
entitled ``Biomarker Qualification: Evidentiary Framework.'' This draft 
guidance provides recommendations on general considerations to address 
when developing a biomarker for qualification under the 21st Century 
Cures Act (Cures Act), enacted on December 13, 2016, that added a new 
section to the Federal Food, Drug, and Cosmetic Act (FD&C Act). 
Qualification of a biomarker is a determination that within the stated 
context of use, the biomarker can be relied on to have a specific 
interpretation and application in drug development and regulatory 
review.

DATES: Submit either electronic or written comments on the draft 
guidance by February 11, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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-2018-D-4267 for ``Biomarker Qualification: Evidentiary Framework; 
Draft Guidance for Industry and FDA Staff.'' Received comments will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at https://www.regulations.gov or at 
the Dockets Management Staff 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 https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. 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: https://www.gpo.gov/

[[Page 63893]]

fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    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, 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 your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Chris Leptak, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6461, Silver Spring, MD 20993-0002, 301-
796-0017.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
and FDA staff entitled ``Biomarker Qualification: Evidentiary 
Framework.'' This draft guidance provides recommendations on general 
considerations to address when developing a biomarker for qualification 
under the Cures Act, enacted on December 13, 2016, that added a new 
section 507, Qualification of Drug Development Tools, to the FD&C Act 
(21 U.S.C. 357).\1\ This guidance discusses the evidentiary framework 
that should be used to support biomarker qualification, as that term is 
now used in section 507 of the FD&C Act, and it was informed by public 
workshops that predated the Cures Act. Specifically, this guidance 
describes the needs assessment, context of use, and benefit-risk 
considerations, and how these considerations can relate to determining 
the type and level of evidence to support qualification of a biomarker. 
This guidance also addresses general statistical and clinical 
considerations related to the correlation between the biomarker and the 
outcome of interest, as well as general analytical considerations 
related to the performance characteristics of the biomarker test.
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    \1\ Section 507 of the FD&C Act was added by section 3011(a) of 
the Cures Act (Pub. L. 114-255).
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    Historically, biomarkers gained acceptance for use in drug 
development after evidence from scientific and medical communities 
accumulated over time, leading to the recognition of the role and value 
of the biomarker in decision making. This evidence was considered as 
part of drug-specific development efforts, and there was no formal 
regulatory process to assess the broader utility of the biomarker 
independent from its use in a specific drug program. Even after the 
Center for Drug Evaluation and Research established the legacy (pre-
Cures Act) Biomarker Qualification Program in 2007, progress in the 
development of biomarkers and their application in drug development has 
been hampered by the lack of a clear, predictable, and specific 
regulatory framework for the evidence sufficient to support regulatory 
decision making using biomarkers. This guidance is an additional step 
towards informing future guidances that will specifically address this 
need, the Cures Act requirements, and commitments from the Prescription 
Drug User Fee Reauthorization Performance Goals and Procedures Fiscal 
Years 2018 through 2022 (PDUFA VI goals letter) \2\.
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    \2\ The PDUFA VI goals letter is available at: https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM511438.pdf.
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    This guidance was informed by several public workshops \3\ that 
discussed the science to support biomarker qualification; these 
workshops convened before the enactment of the Cures Act. Development 
of this guidance was also greatly facilitated by the efforts from the 
biomarker development community--including FDA, National Institutes of 
Health (NIH), industry, academia, patient groups, and the nonprofit 
sector--that developed an October 2016 white paper describing a 
Framework for Defining Evidentiary Criteria for Biomarker 
Qualification.\4\ In addition to considering public comments received 
regarding this guidance, FDA anticipates that the Agency will 
incorporate additional information required under the Cures Act and 
discussed in the PDUFA VI goals letter in a subsequent revised draft 
version of this guidance. Ultimately, FDA anticipates that a future 
revised draft guidance on this topic will meet the statutory 
requirement for guidance on a conceptual framework describing 
appropriate standards and scientific approaches to support the 
development of biomarkers as described in section 3011(b)(1)(A) of the 
Cures Act and meet the commitment in section (1)(J)(6)(d) of the PDUFA 
VI goals letter related to publishing a draft guidance on general 
evidentiary standards for biomarker qualification. As part of FDA's 
efforts to delineate the conceptual framework to support biomarker 
qualification and the general evidentiary standards for biomarker 
qualification, FDA also anticipates that subsequent guidance on 
biomarker qualification will address specific aspects of evidentiary 
considerations (e.g., statistical, analytical) in greater detail. This 
draft guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115).
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    \3\ Workshops convened to discuss the science to support 
biomarker qualification included: Institute of Medicine Workshop on 
Biomarker Qualification (2009), FDA co-sponsored Biomarkers Workshop 
with Howard Hughes Medical Institute (2013), FDA co-sponsored 
Brookings meeting on Advancing the Use of Biomarkers and 
Pharmacogenomics (2014), FDA co-sponsored workshop with M-CERSI and 
the Critical Path Institute on Evidentiary Considerations for 
Integration of Biomarkers in Drug Development (2015), NIH-FDA 
Workshop on Biomarker Glossary of Terms (2015), the National 
Biomarker Development Alliance's Workshop on Collaboratively 
Building a Foundation for FDA Biomarker Qualification (2015), and 
Foundation for the NIH-FDA Workshop on Developing an Evidentiary 
Criteria Framework for Safety Biomarkers Qualification (2016).
    \4\ Biomarkers Consortium Evidentiary Standards Writing Group: 
Framework for Defining Evidentiary Criteria for Biomarker 
Qualification. Final version October 20, 2016. Available at: https://fnih.org/sites/default/files/final/pdf/Evidentiary%20Criteria%20Framework%20Final%20Version%20Oct%2020%202016.pdf.
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    The draft guidance, when finalized, will represent the current 
thinking of FDA on ``Biomarker Qualification: Evidentiary Framework.'' 
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. This 
guidance is not subject to Executive Order 12866.

II. Paperwork Reduction Act of 1995

    This draft 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 parts 312 and 314 have 
been approved under OMB control numbers 0910-0014 and 0910-0001, 
respectively.

III. Electronic Access

[[Page 63894]]

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: December 7, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-26900 Filed 12-11-18; 8:45 am]
BILLING CODE 4164-01-P


