[Federal Register Volume 79, Number 140 (Tuesday, July 22, 2014)]
[Pages 42518-42519]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-17090]



Food and Drug Administration

[Docket No. FDA-2014-N-0926]

Advancing the Use of Biomarkers and Pharmacogenomics; Notice of 
Public Meeting; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public meeting; request for comments.


    The Food and Drug Administration (FDA or the Agency) is announcing 
a public meeting to discuss current scientific and regulatory 
approaches to biomarker development, acceptance, and utility in drug 
and biologic (hereafter referred to as therapeutic product) development 
programs. The purpose of the public meeting is to initiate constructive 
discussion and information sharing on the advancement of biomarker 
science in the context of therapeutic product development among 
relevant stakeholders. Specifically, the meeting will focus on 
identifying challenges for biomarker applications in early- and late-
phase clinical trials and emerging best practices for successful 
biomarker-based programs, including codevelopment of in vitro 
diagnostic devices and use of biomarkers as outcome measures in 
clinical trials. FDA is conducting this meeting in collaboration with 
Brookings Institution. This meeting satisfies an FDA commitment that is 
part of the fifth authorization of the Prescription Drug User Fee Act 
    Date and Time: The meeting will be held on September 5, 2014, from 
9 a.m. to 5 p.m.
    Location: The public meeting will be held at the Washington Plaza 
Hotel, 10 Thomas Circle NW., Washington, DC 20005. For additional 
travel and hotel information, please refer to http://www.brookings.edu/events/2014/09/05-biomarkers-pharmaceutical-FDA. (FDA has verified the 
Web site addresses throughout this notice, but FDA is not responsible 
for subsequent changes to the Web sites after this document publishes 
in the Federal Register).
    Contacts: Padmaja Mummaneni, Food and Drug Administration, Center 
for Drug Evaluation and Research, 10903 New Hampshire Ave., Bldg. 51, 
Rm. 2164, Silver Spring, MD 20993, 301-796-2027, email: 
padmaja.mummaneni@fda.hhs.gov; 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, 240-402-
7911, email: stephen.ripley@fda.hhs.gov.
    Registration: The meeting venue has limited seating. Individuals 
who wish to attend the public meeting must register on or before August 
5, 2014, by visiting http://events.SignUp4.com/PDUFAPublic2014. Early 
registration is recommended. When registering, please provide the 
following information: Name, title, company or organization (if 
applicable), postal address, telephone number, and email address. 
Registration is free and will be on a first-come, first-served basis. 
However, Brookings may limit the number of participants from each 
organization based on space limitations. Onsite registration on the day 
of the meeting by Brookings will be based on space availability.
    If you need special accommodations because of disability, please 
contact Joanna Klatzman at the Brookings Institution (email: 
jklatzman@brookings.edu) at least 7 days before the meeting.
    Streaming Webcast of the Public Meeting: A live Webcast of this 
meeting will be viewable at http://www.brookings.edu/events/2014/09/05-biomarkers-pharmaceutical-FDA on the day of the meeting. A video record 
of the meeting will be available at the same Web address for 1 year.
    Comments: Regardless of attendance at the public meeting, 
interested persons may submit electronic comments to http://www.regulations.gov or written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. It is only necessary to send one set of 
comments. Identify all comments with the corresponding docket number 
found in brackets in the heading of this document. To ensure 
consideration, submit comments by November 5, 2014. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at http://www.regulations.gov. It may 
be viewed at the Division of Dockets Management (see Comments). A 
transcript will also be available in either hard copy or on CD-ROM, 
after submission of a Freedom of Information request. Written requests 
are to be sent to Division of Freedom of Information (ELEM-1029), Food 
and Drug Administration, 12420 Parklawn Dr, Element Bldg., Rockville, 
MD 20857.


I. Background

    On July 9, 2012, the President signed into law the Food and Drug 
Administration Safety and Innovation Act (FDASIA) (Pub. L. 112-144). 
Title I of FDASIA reauthorizes PDUFA and provides FDA with the user fee 
resources necessary to maintain an efficient review process for human 
drug and biological products. The reauthorization of PDUFA includes 
performance goals and procedures for

[[Page 42519]]

the Agency that represents FDA's commitments during fiscal years 2013-
2017. These commitments are fully described in the document entitled 
``PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 
2013 through 2017'' (``PDUFA Goals Letter''), available on FDA's Web 
site at http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM270412.pdf. Section IX of the PDUFA Goals 
Letter, titled Enhancing Regulatory Science and Expediting Drug 
Development,'' includes an enhancement to advance the use of biomarkers 
and pharmacogenomics. As part of this enhancement, FDA committed to 
hold a public meeting to discuss the current status of biomarkers and 
pharmacogenomics and potential strategies to facilitate scientific 
exchanges in regulatory and non-regulatory contexts. The public meeting 
announced by this notice will fulfill this commitment.

II. Purpose and Scope of the Meeting

    The objectives of the meeting are as follows:
     Initiate constructive discussion and information-sharing 
about challenges and best practices in biomarker acceptance and utility 
in the context of therapeutic product development programs,
     share current experience regarding critical issues in the 
transition of exploratory biomarkers to their use in clinical trial 
design and analysis plans, including best practices in the coordination 
of codevelopment of therapeutic products with in vitro diagnostic 
devices, and
     obtain input on evidentiary criteria for biomarkers as 
outcome measures in clinical trials.
    Although many external stakeholders propose using predictive, 
prognostic, pharmacodynamic, or surrogate biomarkers to enhance 
therapeutic product development, the scientific rationale, quality, and 
quantity of supportive data to support the transition from exploratory 
studies to confirmatory trials are variable. This meeting will discuss 
common uses of biomarkers in therapeutic product development programs. 
Discussion topics include specific considerations for early- and late-
phase clinical trials when employing biomarker-based trial designs, 
emerging best practices in codevelopment of therapeutic products with 
in vitro diagnostic devices, and discussion of context-specific 
scenarios in which biomarkers may be used as outcome measures.
    The public input from the meeting will be used to identify 
opportunities for biomarker-related regulatory guidance, improve 
understanding and consistency in regulatory review of therapeutic 
product applications that incorporate biomarkers in clinical trial 
designs, and identify potential strategies to facilitate scientific 
exchanges in regulatory and non-regulatory contexts.

III. Scope of Public Input Requested

    FDA seeks input on a range of topics related to common challenges 
and emerging strategies for application of biomarkers in clinical 
trials, whether for patient selection or as an outcome measure in 
therapeutic product development. Potential topics for discussion 
include the following:

1. Critical Issues in the Transition of Exploratory Biomarkers to 
Companion Diagnostic Devices

     Early-phase trial designs and exploratory biomarker 
analysis approaches to effectively inform whether biomarker-enriched 
confirmatory trial strategies or other strategies are appropriate,
     evidentiary standards for incorporating novel biomarkers 
into the design and analysis of pre-marketing confirmatory trials 
(e.g., for patient selection), and need for and timing of data 
collection in non-targeted populations,
     prospective/retrospective approaches to validate 
biomarkers in the context of confirmatory trials,
     approaches to establish and modify thresholds for 
quantitative biomarkers prior to conducting confirmatory trials,
     best practices for biospecimen collection and in vitro 
diagnostic assay development in early-phase therapeutic trials to 
support subsequent biomarker/diagnostic codevelopment,
     best practices for effective communication between 
regulatory agencies and therapeutic or diagnostic sponsors in the 
setting of codevelopment, and
     codevelopment considerations for biomarkers that are 
predictive, but not necessarily essential to the safe and effective use 
of the therapeutic product.

2. Use of a Biomarker as a Clinical Trial Outcome Measure

     Criteria for consideration of biomarker outcomes in 
clinical trials as correlates,
     principles to consider for biomarker outcomes as 
replacement endpoints of clinical endpoints considering the following:
    [cir] Multiple causal pathways of a disease process,
    [cir] biomarker endpoint is not in the causal pathway of the 
disease process,
    [cir] interventions with mechanisms of action independent of the 
disease process,
     evidence for a compelling context for the use of a 
biomarker as a surrogate endpoint, and
     roles, if any, on metaanalysis of clinical trials data to 
establish the utility of biomarker outcomes as surrogates.
    In this Federal Register notice, FDA has included specific issues 
that will be addressed by the presenters and panelists. Time will be 
reserved during the meeting for general comments and questions from the 
audience following the panel discussions. FDA will do its best to 
accommodate requests to speak.
    The agenda and background materials will be available approximately 
2 weeks before the meeting at http://www.brookings.edu/events/2014/09/05-biomarkers-pharmaceutical-FDA.

    Dated: July 16, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-17090 Filed 7-21-14; 8:45 am]