83 FR 63892 - Biomarker Qualification: Evidentiary Framework; Draft Guidance for Industry and Food and Drug Administration Staff; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 238 (December 12, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 238 (December 12, 2018)
| Page Range | 63892-63894 | |
| FR Document | 2018-26900 |
[Federal Register Volume 83, Number 238 (Wednesday, December 12, 2018)] [Notices] [Pages 63892-63894] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-26900] ----------------------------------------------------------------------- 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SERVICES Food and Drug Administration [Docket No. FDA-2018-D-4267] Biomarker Qualification: Evidentiary Framework; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS.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. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry and FDA staff entitled ``Biomarker Qualification: Evidentiary Framework.'' This draft guidance provides recommendations on general considerations to address when developing a biomarker for qualification under the 21st Century Cures Act (Cures Act),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 DATES: Submit either electronic or written comments on the draft guidance by February 11, 2019 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.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.thefederalregister.org/ [[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. --------------------------------------------------------------------------- \1\ Section 507 of the FD&C Act was added by section 3011(a) of the Cures Act (Pub. L. 114-255). --------------------------------------------------------------------------- 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\. --------------------------------------------------------------------------- \2\ The PDUFA VI goals letter is available at: https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM511438.pdf. --------------------------------------------------------------------------- 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). --------------------------------------------------------------------------- \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. --------------------------------------------------------------------------- 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
![63892 Federal Register / Vol. 83, No. 238 / Wednesday, December 12, 2018 / Notices
20201. Telephone: 202–795–7334. Fax: DEPARTMENT OF HEALTH AND do not wish to be made available to the
202–795–7334. Email: allison.cruz@ HUMAN SERVICES public, submit the comment as a
acl.hhs.gov. written/paper submission and in the
Food and Drug Administration manner detailed (see ‘‘Written/Paper
SUPPLEMENTARY INFORMATION: The Submissions’’ and ‘‘Instructions’’).
[Docket No. FDA–2018–D–4267]
purpose of this virtual meeting is to
discuss the Committee’s preparation of Written/Paper Submissions
Biomarker Qualification: Evidentiary
the 2019 Report to the President, Framework; Draft Guidance for Submit written/paper submissions as
including its content and format, and Industry and Food and Drug follows:
related data collection and analysis Administration Staff; Availability • Mail/Hand Delivery/Courier (for
required to complete the writing of the written/paper submissions): Dockets
AGENCY: Food and Drug Administration, Management Staff (HFA–305), Food and
Report. This meeting was originally
HHS. Drug Administration, 5630 Fishers
scheduled for December 5 from 9:00–
ACTION: Notice of availability. Lane, Rm. 1061, Rockville, MD 20852.
10:00 a.m. (EST). This meeting is
rescheduled to December 12 from 9:00– SUMMARY: The Food and Drug • For written/paper comments
10:00 a.m. (EST) due to the closure of Administration (FDA or Agency) is submitted to the Dockets Management
Federal offices on December 5 and to announcing the availability of a draft Staff, FDA will post your comment, as
allow for the call to occur before the end guidance for industry and FDA staff well as any attachments, except for
of year. entitled ‘‘Biomarker Qualification: information submitted, marked and
Evidentiary Framework.’’ This draft identified, as confidential, if submitted
Agenda: The Committee will discuss as detailed in ‘‘Instructions.’’
the preparation of the PCPID 2019 guidance provides recommendations on
general considerations to address when Instructions: All submissions received
Report to the President, including its must include the Docket No. FDA–
developing a biomarker for qualification
content and format, and related data 2018–D–4267 for ‘‘Biomarker
under the 21st Century Cures Act (Cures
collection and analysis required to Qualification: Evidentiary Framework;
Act), enacted on December 13, 2016,
complete the writing of the Report. that added a new section to the Federal Draft Guidance for Industry and FDA
Webinar/Conference Call: The Food, Drug, and Cosmetic Act (FD&C Staff.’’ Received comments will be
webinar/conference call is scheduled for Act). Qualification of a biomarker is a placed in the docket and, except for
Wednesday, December 12, 2018, 9:00 determination that within the stated those submitted as ‘‘Confidential
a.m. to 10:00 a.m. (EST) and may end context of use, the biomarker can be Submissions,’’ publicly viewable at
early if discussions are finished. relied on to have a specific https://www.regulations.gov or at the
interpretation and application in drug Dockets Management Staff between 9
Instructions to Participate in the
development and regulatory review. a.m. and 4 p.m., Monday through
Webinar/Conference Call on Friday.
Wednesday, December 12, 2018: Please DATES: Submit either electronic or
written comments on the draft guidance • Confidential Submissions—To
dial: (888) 949–2790; Pass Code: submit a comment with confidential
1989852. by February 11, 2019 to ensure that the
Agency considers your comment on this information that you do not wish to be
Background Information on the draft guidance before it begins work on made publicly available, submit your
Committee: The PCPID acts in an the final version of the guidance. comments only as a written/paper
advisory capacity to the President and ADDRESSES: You may submit comments submission. You should submit two
the Secretary of Health and Human on any guidance at any time as follows: copies total. One copy will include the
Services on a broad range of topics information you claim to be confidential
relating to programs, services and Electronic Submissions with a heading or cover note that states
support for individuals with intellectual Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS
disabilities. The PCPID executive order following way: CONFIDENTIAL INFORMATION.’’ The
stipulates that the Committee shall: (1) • Federal eRulemaking Portal: Agency will review this copy, including
Provide such advice concerning https://www.regulations.gov. Follow the the claimed confidential information, in
intellectual disabilities as the President instructions for submitting comments. its consideration of comments. The
or the Secretary of Health and Human Comments submitted electronically, second copy, which will have the
including attachments, to https:// claimed confidential information
Services may request; and (2) provide
www.regulations.gov will be posted to redacted/blacked out, will be available
advice to the President concerning the
the docket unchanged. Because your for public viewing and posted on
following for people with intellectual
comment will be made public, you are https://www.regulations.gov. Submit
disabilities: (A) Expanding employment both copies to the Dockets Management
solely responsible for ensuring that your
opportunities; (B) connecting people to Staff. If you do not wish your name and
comment does not include any
services; (C) supporting families and confidential information that you or a contact information to be made publicly
caregivers; (D) strengthening the third party may not wish to be posted, available, you can provide this
networks; and (E) protecting rights and such as medical information, your or information on the cover sheet and not
preventing abuse. anyone else’s Social Security number, or in the body of your comments and you
Dated: December 6, 2018. confidential business information, such must identify this information as
as a manufacturing process. Please note ‘‘confidential.’’ Any information marked
amozie on DSK3GDR082PROD with NOTICES1
Julie Hocker,
that if you include your name, contact as ‘‘confidential’’ will not be disclosed
Commissioner, Administration on Disabilities
(AoD). information, or other information that except in accordance with 21 CFR 10.20
identifies you in the body of your and other applicable disclosure law. For
[FR Doc. 2018–26857 Filed 12–11–18; 8:45 am]
comments, that information will be more information about FDA’s posting
BILLING CODE 4154–01–P of comments to public dockets, see 80
posted on https://www.regulations.gov.
• If you want to submit a comment FR 56469, September 18, 2015, or access
with confidential information that you the information at: https://www.gpo.gov/
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![63894 Federal Register / Vol. 83, No. 238 / Wednesday, December 12, 2018 / Notices
Persons with access to the internet draft guidance before it begins work on comments only as a written/paper
may obtain the draft guidance at either the final version of the guidance. submission. You should submit two
https://www.fda.gov/Drugs/ ADDRESSES: You may submit comments copies total. One copy will include the
GuidanceComplianceRegulatory on any guidance at any time as follows: information you claim to be confidential
Information/Guidances/default.htm or with a heading or cover note that states
https://www.regulations.gov. Electronic Submissions ‘‘THIS DOCUMENT CONTAINS
Dated: December 7, 2018.
Submit electronic comments in the CONFIDENTIAL INFORMATION.’’ The
following way: Agency will review this copy, including
Leslie Kux,
• Federal eRulemaking Portal: the claimed confidential information, in
Associate Commissioner for Policy. https://www.regulations.gov. Follow the its consideration of comments. The
[FR Doc. 2018–26900 Filed 12–11–18; 8:45 am] instructions for submitting comments. second copy, which will have the
BILLING CODE 4164–01–P Comments submitted electronically, claimed confidential information
including attachments, to https:// redacted/blacked out, will be available
www.regulations.gov will be posted to for public viewing and posted on
DEPARTMENT OF HEALTH AND the docket unchanged. Because your https://www.regulations.gov. Submit
HUMAN SERVICES comment will be made public, you are both copies to the Dockets Management
solely responsible for ensuring that your Staff. If you do not wish your name and
Food and Drug Administration
comment does not include any contact information to be made publicly
confidential information that you or a available, you can provide this
[Docket No. FDA–2015–D–4750] third party may not wish to be posted, information on the cover sheet and not
such as medical information, your or in the body of your comments and you
The ‘‘Deemed to be a License’’ anyone else’s Social Security number, or
Provision of the BPCI Act: Questions must identify this information as
confidential business information, such ‘‘confidential.’’ Any information marked
and Answers; Draft Guidance for as a manufacturing process. Please note
Industry; Availability; Request for as ‘‘confidential’’ will not be disclosed
that if you include your name, contact except in accordance with 21 CFR 10.20
Comments on Preliminary List of information, or other information that
Affected Applications and other applicable disclosure law. For
identifies you in the body of your more information about FDA’s posting
AGENCY: Food and Drug Administration, comments, that information will be of comments to public dockets, see 80
HHS. posted on https://www.regulations.gov. FR 56469, September 18, 2015, or access
• If you want to submit a comment the information at: https://www.gpo.gov/
ACTION:Notice of availability; request
with confidential information that you fdsys/pkg/FR-2015-09-18/pdf/2015-
for comments.
do not wish to be made available to the 23389.pdf.
SUMMARY: The Food and Drug public, submit the comment as a Docket: For access to the docket to
Administration (FDA or Agency) is written/paper submission and in the read background documents or the
announcing the availability of a draft manner detailed (see ‘‘Written/Paper electronic and written/paper comments
guidance for industry entitled ‘‘The Submissions’’ and ‘‘Instructions’’). received, go to https://
‘Deemed to be a License’ Provision of Written/Paper Submissions www.regulations.gov and insert the
the BPCI Act: Questions and Answers.’’ docket number, found in brackets in the
Submit written/paper submissions as
This draft guidance is intended to heading of this document, into the
follows:
provide answers to common questions ‘‘Search’’ box and follow the prompts
• Mail/Hand delivery/Courier (for
about FDA’s interpretation of the and/or go to the Dockets Management
written/paper submissions): Dockets
statutory provision under which an Staff, 5630 Fishers Lane, Rm. 1061,
Management Staff (HFA–305), Food and
application for a biological product Rockville, MD 20852.
Drug Administration, 5630 Fishers
approved under the Federal Food, Drug, You may submit comments on any
Lane, Rm. 1061, Rockville, MD 20852.
and Cosmetic Act (FD&C Act) as of • For written/paper comments guidance at any time (see 21 CFR
March 23, 2020, will be deemed to be submitted to the Dockets Management 10.115(g)(5)).
a license for the biological product Staff, FDA will post your comment, as Submit written requests for single
under the Public Health Service Act well as any attachments, except for copies of this draft guidance to the
(PHS Act) on March 23, 2020. This information submitted, marked and Division of Drug Information, Center for
guidance also describes FDA’s identified, as confidential, if submitted Drug Evaluation and Research, Food
compliance policy for the labeling of as detailed in ‘‘Instructions.’’ and Drug Administration, 10001 New
biological products that will be the Instructions: All submissions received Hampshire Ave., Hillandale Building,
subject of deemed biologics license must include the Docket No. FDA– 4th Floor, Silver Spring, MD 20993–
applications (BLAs). This guidance is 2015–D–4750 for ‘‘The ‘Deemed to be a 0002; or to the Office of
intended to facilitate planning for the License’ Provision of the BPCI Act: Communication, Outreach and
March 23, 2020, transition date and Questions and Answers; Draft Guidance Development, Center for Biologics
provide further clarity regarding the for Industry.’’ Received comments will Evaluation and Research, Food and
Agency’s interpretation of this statutory be placed in the docket and, except for Drug Administration, 10903 New
provision. FDA also invites comment on those submitted as ‘‘Confidential Hampshire Ave., Bldg. 71, Rm. 3128,
the preliminary list of approved new Submissions,’’ publicly viewable at Silver Spring, MD 20993–0002. Send
drug applications (NDAs) for biological https://www.regulations.gov or at the one self-addressed adhesive label to
amozie on DSK3GDR082PROD with NOTICES1
products under the FD&C Act that will Dockets Management Staff between 9 assist that office in processing your
be deemed to be BLAs on the transition a.m. and 4 p.m., Monday through requests. See the SUPPLEMENTARY
date. Friday. INFORMATION section for electronic
DATES: Submit either electronic or • Confidential Submissions—To access to the draft guidance document.
written comments on the draft guidance submit a comment with confidential FOR FURTHER INFORMATION CONTACT:
by February 11, 2019 to ensure that the information that you do not wish to be Janice Weiner, Center for Drug
Agency considers your comment on this made publicly available, submit your Evaluation and Research, Food and
VerDate Sep<11>2014 18:39 Dec 11, 2018 Jkt 247001 PO 00000 Frm 00070 Fmt 4703 Sfmt 4703 E:\FR\FM\12DEN1.SGM 12DEN1](https://thefederalregister.org/doc/83_FR_64130/page/3.svg)
Document Created: 2018-12-12 01:39:37
Document Modified: 2018-12-12 01:39:37
| 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 of availability. | |
| 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. | |
| 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. | |
| FR Citation | 83 FR 63892 |
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