80 FR 8089 - Identifying Potential Biomarkers for Qualification and Describing Contexts of Use To Address Areas Important to Drug Development; Request for Comments
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 80, Issue 30 (February 13, 2015)
Food and Drug Administration
Federal Register Volume 80, Issue 30 (February 13, 2015)
| Page Range | 8089-8091 | |
| FR Document | 2015-02976 |
[Federal Register Volume 80, Number 30 (Friday, February 13, 2015)] [Notices] [Pages 8089-8091] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-02976] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2014-N-2187] Identifying Potential Biomarkers for Qualification and Describing Contexts of Use To Address Areas Important to Drug Development; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is seeking information to facilitate development and qualification of biomarkers in areas related to human drug therapeutics. Towards this goal, FDA is encouraging interested groups and individuals to submit information on specific medical and biological areas where novel biomarkers can be identified that would meaningfully advance drug development. FDA encourages respondents to describe evidentiary considerations that are important to qualify these biomarkers for a specific context of use. Details of information that should be provided to the Agency are described in the survey. DATES: Submit either electronic or written comments by April 14, 2015. ADDRESSES: You may submit comments by any of the following methods: Electronic Submissions Submit electronic comments in either of the following ways:Federal eRulemaking Portal: http://www.regulations.gov. Follow the instructions for submitting comments. SurveyMonkey Link: https://www.surveymonkey.com/s/RHJLHS7. This survey may be used to provide feedback on answers to questions regarding potential biomarkers for qualification and to describe contexts of use to address areas important to drug development. Written Submissions Submit written submissions in the following ways: Mail/Hand delivery/Courier (for paper submissions): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Instructions: All submissions received must include the Docket No. FDA-2014-N-2187 for this document. All comments received may be posted without change to http://www.regulations.gov, including any personal information provided. It is only necessary to send one set of comments. For additional information on submitting comments, see the ``Request for Information'' heading of the SUPPLEMENTARY INFORMATION section of this document. Docket: For access to the docket to read background documents or 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, between 9 a.m. and 4 p.m., Monday through Friday. FOR FURTHER INFORMATION CONTACT: Marianne Noone, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 21, Rm. 4528, Silver Spring, MD 20993-0002, 301-796-7495. [[Page 8090]] SUPPLEMENTARY INFORMATION: I. Background The President signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA) (Pub. L. 112-144) on July 9, 2012. Title I of FDASIA reauthorizes the Prescription Drug User Fee Act (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 added performance goals and procedures for the Agency that represent FDA's commitments during fiscal years 2013 through 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 entitled ``Enhancing Regulatory Science and Expediting Drug Development'' references support for the identification and advancement of biomarkers. A biomarker is an objective characteristic that is measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to treatment. Biomarkers can serve many purposes in clinical drug development, including the following: Defining the appropriate patient populations for study, as well as those who should receive the drug in clinical practice; pharmacodynamic markers for proof of concept and dose selection; and pharmacodynamic markers of adverse effects. A subset of pharmacodynamic biomarkers can serve as replacements for clinical efficacy endpoints that reflect how a patient feels, functions, or survives. The path to development of promising therapeutics can be enabled by the availability of biomarkers that are analytically validated and clinically qualified for a specific context of use (i.e., a comprehensive, clear, and precise statement that describes the manner of use, interpretation, and purpose of use of a biomarker in drug development). Qualification is based on a body of evidence that demonstrates that the biomarkers are fit for purpose in drug development and evaluation (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/ucm284076.htm). Further, qualification is dependent on the specific proposed context of use. Biomarkers that are qualified can help to progressively reduce uncertainty about the outcome of clinical development programs. Public/private partnerships involving regulatory, academic, and industry scientists, collaborating within a precompetitive framework, are essential to catalyzing progress. Because of limitations in resources, such efforts must be focused on the opportunities that offer the greatest potential for impact. FDA intends to facilitate identification of the most promising biomarkers and the areas important to drug development and to promote efforts that will aid in the qualification and regulatory adoption of the drug development framework. II. Request for Information FDA is seeking public feedback to identify promising biomarker candidates in areas important to drug development and to identify considerations for evidence needed to qualify various types of biomarkers for specific contexts of use. FDA requests identification of specific biomarkers with a proposed context of use and of the type of evidence needed to support qualification. After reviewing the information provided, FDA will post the collated information on its Web site. A. Information Requirements In general, submitted information should include the following for each biomarker nominated, as well as any other relevant information: Areas that have a critical need for biomarkers to assist drug development; The name of the biomarker; The proposed context of use for the biomarker (if known); The reason why the biomarker should be considered, taking into account its usefulness as a drug development tool; and Any evidence that should be developed to support qualification of the biomarker. B. Questions and Requests Specific questions and requests are as follows: 1. Are there specific aspects of drug development that could be enhanced through the development of biomarkers? a. Please list the specific applications of biomarkers that address areas important to drug development. b. Please list the specific areas (for example, a specific disease area or an organ toxicity) needed for development of biomarkers important to drug development. c. Is there information or efforts which could be leveraged to advance these areas? If yes, please describe. d. Are there areas that appear to be promising for the development of new biomarkers and for which collaborative engagement from stakeholders offers a path forward? If so, please explain. Are there groups positioned to accomplish this? If yes, please describe. e. Are there barriers that preclude engagement or investment in biomarkers for these priority areas? If yes, please explain. 2. In each of these priority areas that are important to drug development, please provide the following information: a. Biomarker: What specific biomarkers do you believe represent the greatest near-term opportunity to establish utility in drug development (i.e., that could be substantially advanced by facilitating discussion and consensus building)? b. Rationale: Why should the biomarker(s) be included on the list, taking into account its usefulness in regulatory decisionmaking as a drug development tool? c. Context of use: Can you please describe/propose a specific context of use for the biomarker(s)? d. Evidentiary gaps: To support the proposed context of use, what do you see as the largest evidentiary gaps that need to be addressed to permit ``fit for purpose'' qualification? e. How can these evidentiary gaps be addressed? f. Collaborative data sharing: Can any of these gaps be addressed by collaborative data sharing of existing data versus prospective studies specifically dedicated to addressing the gap? 3. Please indicate your affiliation from the following list: Academia, pharmaceutical sector, biotechnology sector, government, professional organization, non-profit organization, clinician, patient advocacy group, patient, or other (please provide specifics, if you choose other). III. Paperwork Reduction Act This Federal Register notice requests input from biomarker experts from academia, the pharmaceutical industry, and government organizations on the evidentiary standards for biomarkers or on the expectations about data for qualification of different types of biomarkers. This request is exempt from the Office of Management and Budget's review under 5 CFR 1320.3(h)(4): Facts or opinions submitted in response to general solicitations of comments from the public, published in the Federal Register or other publications, regardless of the form or format thereof, [[Page 8091]] provided that no person is required to supply specific information pertaining to the commenter, other than that necessary for self- identification, as a condition of the Agency's full consideration of the comment. Dated: February 5, 2015. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2015-02976 Filed 2-12-15; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 80, No. 30 / Friday, February 13, 2015 / Notices 8089
opioid antagonist with high affinity for information, or analysis to support this where novel biomarkers can be
the mu opioid receptor. The naloxone is claim. Based on our independent review identified that would meaningfully
intended to be inactive when of the available data and the published advance drug development. FDA
SUBOXONE is used appropriately, but studies on the relative abuse liability of encourages respondents to describe
to precipitate more severe withdrawal SUBUTEX and SUBOXONE, we do not evidentiary considerations that are
symptoms if the product is crushed and have sufficient information at this time important to qualify these biomarkers
injected by an individual dependent on to determine that SUBUTEX poses an for a specific context of use. Details of
full opioid agonists. A variety of factors increased potential for abuse or misuse information that should be provided to
such as degree of opioid dependence, relative to SUBOXONE. Furthermore, as the Agency are described in the survey.
relative amount of buprenorphine discussed previously, SUBUTEX has DATES: Submit either electronic or
exposure, and route of administration important therapeutic benefits for written comments by April 14, 2015.
influence the antagonist effect of certain patient populations that may not ADDRESSES: You may submit comments
naloxone. As a result, buprenorphine/ tolerate or should not be exposed to the by any of the following methods:
naloxone combination products may not naloxone in SUBOXONE.
have the same effect on non-dependent For these reasons, based on the data Electronic Submissions
opioid abusers or abusers of and information available to the Agency Submit electronic comments in either
buprenorphine. As stated in the at this time, we find that the benefits of of the following ways:
approved SUBOXONE labeling in SUBUTEX continue to outweigh the • Federal eRulemaking Portal: http://
section 12.2, ‘‘naloxone in risks. Therefore, we conclude that www.regulations.gov. Follow the
buprenorphine/naloxone tablets may SUBUTEX was not withdrawn from sale instructions for submitting comments.
deter injection of buprenorphine/ for reasons of safety or effectiveness. • SurveyMonkey Link: https://
naloxone tablets by persons with active Accordingly, the Agency will www.surveymonkey.com/s/RHJLHS7.
substantial heroin or other full mu- continue to list SUBUTEX in the This survey may be used to provide
opioid dependence,’’ but ‘‘some opioid- ‘‘Discontinued Drug Product List’’ feedback on answers to questions
dependent persons, particularly those section of the Orange Book. The regarding potential biomarkers for
with a low level of full mu-opioid ‘‘Discontinued Drug Product List’’ qualification and to describe contexts of
physical dependence or those whose delineates, among other items, drug use to address areas important to drug
opioid physical dependence is products that have been discontinued development.
predominantly to buprenorphine, abuse from marketing for reasons other than
buprenorphine/naloxone combinations safety or effectiveness. FDA will not Written Submissions
by the intravenous or intranasal route.’’ begin procedures to withdraw approval Submit written submissions in the
SUBUTEX has important therapeutic of ANDAs that refer to SUBUTEX. Such following ways:
benefits for certain patient populations ANDAs may continue to be approved by • Mail/Hand delivery/Courier (for
that may not tolerate or should not be the Agency as long as they meet all paper submissions): Division of Dockets
exposed to the naloxone in SUBOXONE. other legal and regulatory requirements Management (HFA–305), Food and Drug
Specifically, as explained in section for the approval of ANDAs. Administration, 5630 Fishers Lane, Rm.
5.11 of the approved labeling for 1061, Rockville, MD 20852.
SUBOXONE, ‘‘[b]uprenorphine/ Dated: February 9, 2015.
Instructions: All submissions received
naloxone products are not Leslie Kux,
must include the Docket No. FDA–
recommended in patients with severe Associate Commissioner for Policy. 2014–N–2187 for this document. All
hepatic [liver] impairment and may not [FR Doc. 2015–03001 Filed 2–12–15; 8:45 am] comments received may be posted
be appropriate for patients with BILLING CODE 4164–01–P without change to http://
moderate hepatic impairment.’’ Section www.regulations.gov, including any
5.11 further states that ‘‘hepatic personal information provided. It is
impairment results in a reduced DEPARTMENT OF HEALTH AND only necessary to send one set of
clearance of naloxone to a much greater HUMAN SERVICES comments. For additional information
extent than buprenorphine,’’ and thus, on submitting comments, see the
‘‘patients with severe hepatic Food and Drug Administration
‘‘Request for Information’’ heading of
impairment will be exposed to [Docket No. FDA–2014–N–2187] the SUPPLEMENTARY INFORMATION section
substantially higher levels of naloxone of this document.
than patients with normal hepatic Identifying Potential Biomarkers for Docket: For access to the docket to
function.’’ SUBUTEX also is preferred to Qualification and Describing Contexts read background documents or
SUBOXONE for patients transitioning of Use To Address Areas Important to comments received, go to http://
from treatment with methadone or other Drug Development; Request for www.regulations.gov and insert the
long-acting opioid products because Comments docket number, found in brackets in the
they are at higher risk for precipitated
AGENCY: Food and Drug Administration, heading of this document, into the
and prolonged withdrawal, and the
HHS. ‘‘Search’’ box and follow the prompts
naloxone in buprenorphine/naloxone
and/or go to the Division of Dockets
combination products may cause worse ACTION: Notice; request for comments. Management, 5630 Fishers Lane, Rm.
withdrawal in this population.
Although Reckitt has publicly stated SUMMARY: The Food and Drug 1061, Rockville, MD 20852, between 9
that SUBUTEX ‘‘creates a greater risk of Administration (FDA or Agency) is a.m. and 4 p.m., Monday through
Friday.
tkelley on DSK3SPTVN1PROD with NOTICES
misuse, abuse, and diversion’’ than seeking information to facilitate
SUBOXONE (please refer to letter from development and qualification of FOR FURTHER INFORMATION CONTACT:
Reckitt to Health Care Providers, biomarkers in areas related to human Marianne Noone, Center for Devices and
available at http:// drug therapeutics. Towards this goal, Radiological Health, Food and Drug
buprenorphine.samhsa.gov/ FDA is encouraging interested groups Administration, 10903 New Hampshire
SubutexDiscontinuation9-16-11.pdf), and individuals to submit information Ave., Bldg. 21, Rm. 4528, Silver Spring,
Reckitt has not submitted any data, on specific medical and biological areas MD 20993–0002, 301–796–7495.
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![Federal Register / Vol. 80, No. 30 / Friday, February 13, 2015 / Notices 8091
provided that no person is required to opportunity to speak, please send a brief Currently, the conditional approval
supply specific information pertaining summary of your comments. Early provisions allow an applicant to market
to the commenter, other than that registration for the meeting is a new animal drug intended for a minor
necessary for self-identification, as a encouraged due to limited time and species or a minor use in a major
condition of the Agency’s full space. species after the applicant has
consideration of the comment. demonstrated that the drug is safe and
SUPPLEMENTARY INFORMATION: can be manufactured according to
Dated: February 5, 2015.
I. Background standards applicable to approval of
Leslie Kux,
applications under section 512(b)(1) of
Associate Commissioner for Policy. FDA considers the timely review of the Federal Food, Drug, and Cosmetic
[FR Doc. 2015–02976 Filed 2–12–15; 8:45 am] the safety and effectiveness of new Act (21 U.S.C. 360b(b)(1)). FDA and
BILLING CODE 4164–01–P animal drugs to be central to the members of regulated industry jointly
Agency’s mission to protect and agreed to explore, as part of the
promote the public health. Before 2004, performance goals outlined in the
DEPARTMENT OF HEALTH AND the timeliness and predictability of the ADUFA III goals letter, statutory
HUMAN SERVICES new animal drug review program was a changes to expand the use of
concern. The Animal Drug User Fee Act conditional approval to other
Food and Drug Administration enacted in 2003 (Pub. L. 108–130; appropriate categories of new animal
[Docket No. FDA–2014–N–1049] hereinafter referred to as ‘‘ADUFA I’’), drugs.
authorized FDA to collect user fees for This public meeting is intended to
Conditional Approval of New Animal 5 years—fiscal year (FY) 2004 to FY provide an additional opportunity for
Drugs; Public Meeting; Request for 2008—that were to be dedicated to public comment. The Agency is
Comments expediting the review of new animal especially interested in receiving
drug applications according to certain comments during the meeting on the
AGENCY: Food and Drug Administration, categories of new animal drug
performance goals and to expand and
HHS. applications that would be considered
modernize the new animal drug review
ACTION: Notification of public meeting; program. The Agency agreed to meet a ‘‘appropriate’’ and why; concerns, if
request for comments. comprehensive set of performance goals any, that might arise due to the
established to show significant expansion of the Conditional Approval
The Food and Drug Administration process; and the length of marketing
(FDA) is announcing a public meeting to improvement in the timeliness and
predictability of the new animal drug exclusivity, if any, that should be
explore the use of statutory changes to associated with the expansion of the
expand the use of conditional approval review process. The implementation of
ADUFA I provided a significant funding Conditional Approval process.
to additional categories of new animal FDA will consider comments received
drugs. This policy exploration is increase that enabled FDA to increase
the number of staff dedicated to the new at this meeting as it moves forward with
consistent with a stated performance this process.
goal in the Animal Drug User Fee animal drug application review process.
FDA has already opened public
Amendments of 2013 (ADUFA III) goals In 2008, before ADUFA I expired, docket FDA Docket No. FDA–2014–N–
letter. FDA is requesting that you submit Congress passed the Animal Drug User 1049 to receive comments on the issue
any comments related to this issue by Fee Amendments of 2008 (Pub. L. 110– (79 FR 53430, September 9, 2014).
September 30, 2015. 316; hereinafter referred to as ‘‘ADUFA Although you can comment on this
Date and Time: The public meeting II’’), which included an extension of document at any time, to ensure that the
will be held on March 16, 2015, from 1 ADUFA for an additional 5 years—FY Agency considers your comment before
p.m. until 4 p.m. 2009 to FY 2013. ADUFA II finalizing work on the exploration
Location: The public meeting will be performance goals were established process described in this document,
held at the Center for Veterinary based on ADUFA I FY 2008 review submit either electronic or written
Medicine, Food and Drug timeframes. In addition, FDA provided comments by September 30, 2015.
Administration, 7519 Standish Pl., 3rd program enhancements to reduce review
Floor, Rockville, MD 20855. Parking is cycles and improve communications II. Participation in a Public Meeting
free. during reviews. While oral presentations from specific
Contact Person: Laura Bradbard, In 2013, before ADUFA II expired, individuals and organizations may be
Center for Veterinary Medicine, Food Congress passed ADUFA III (Pub. L. limited due to time constraints during
and Drug Administration, 7519 Standish 113–14), which was signed by the the public meeting, stakeholders may
Pl., Rm. 159, Rockville, MD 20855, 240– President on June 13, 2013. Like its submit electronic or written comments
276–9109, FAX: 240–276–9020, email: predecessors, ADUFA III includes its discussing any issues of concern to the
Laura.Bradbard@fda.hhs.gov. own comprehensive set of performance administration record (the docket). All
Registration: Registration is free and goals. One such goal, as stated in the relevant data and documentation should
available on a first-come, first-served ADUFA III goals letter, is: Beginning in be submitted with the comments to
basis. Persons interested in attending early FY 2014, the Agency agrees to Docket No. FDA–2014–N–1049. Submit
this meeting must register by March 10, explore, in concert with industry, the electronic comments to http://
2015. For general questions about the feasibility of pursuing statutory www.regulations.gov. Submit written
meeting, for assistance to register for the revisions, consistent with the Agency’s comments to the Division of Dockets
tkelley on DSK3SPTVN1PROD with NOTICES
meeting, to request an opportunity to mission to protect and promote the Management (HFA–305), Food and Drug
make an oral presentation, or to request public health, that may expand the use Administration, 5630 Fishers Lane, rm.
special accommodations due to a of conditional approvals to other 1061, Rockville, MD 20852. It is only
disability, contact Laura Bradbard (see appropriate categories of new animal necessary to send one set of comments.
Contact Person). Please include your drug applications and develop Identify comments with the docket
name, organization, and contact recommendations by September 30, number FDA–2014–N–1049. Received
information. If you are requesting an 2015. comments may be seen in the Division
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Document Created: 2015-12-18 13:17:47
Document Modified: 2015-12-18 13:17:47
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice; request for comments. | |
| Dates | Submit either electronic or written comments by April 14, 2015. | |
| Contact | Marianne Noone, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 21, Rm. 4528, Silver Spring, MD 20993-0002, 301-796-7495. | |
| FR Citation | 80 FR 8089 |
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