[Federal Register Volume 83, Number 72 (Friday, April 13, 2018)]
[Notices]
[Pages 16110-16112]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-07686]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-D-1233]
Use of Public Human Genetic Variant Databases To Support Clinical
Validity for Genetic and Genomic-Based In Vitro Diagnostics; Guidance
for Stakeholders 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 the final guidance entitled ``Use of Public Human
Genetic Variant Databases to Support Clinical Validity for Genetic and
Genomic-Based In Vitro Diagnostics; Guidance for Stakeholders and Food
and Drug Administration Staff.'' This guidance document describes how
publicly accessible databases of human genetic variants can serve as
sources of valid scientific evidence to support the clinical validity
of genotype-phenotype relationships in FDA's regulatory review of
genetic and genomic-based tests. This guidance further outlines the
process by which administrators of genetic variant databases could
voluntarily apply to FDA for recognition, and how FDA would review such
applications and periodically reevaluate recognized databases.
DATES: The announcement of the guidance is published in the Federal
Register on April 13, 2018.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances 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-2016-D-1233 for ``Use of Public Human Genetic Variant Databases to
Support Clinical Validity for Genetic and Genomic-Based In Vitro
Diagnostics; Guidance for Stakeholders and Food and Drug Administration
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 office
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/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
[[Page 16111]]
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)).
An electronic copy of the guidance document is available for
download from the internet. See the SUPPLEMENTARY INFORMATION section
for information on electronic access to the guidance. Submit written
requests for a single hard copy of the guidance document entitled ``Use
of Public Human Genetic Variant Databases to Support Clinical Validity
for Genetic and Genomic-Based In Vitro Diagnostics; Guidance for
Stakeholders and Food and Drug Administration Staff '' to the Office of
the Center Director, Guidance and Policy Development, Center for
Devices and Radiological Health, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 66, Rm. 5431, Silver Spring, MD 20993-0002,
or the Office of Communication, Outreach, and Development, Center for
Biologics Evaluation and Research, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002.
Send one self-addressed adhesive label to assist that office in
processing your request.
FOR FURTHER INFORMATION CONTACT: Laura Koontz, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4553, Silver Spring, MD 20993-0002, 301-796-7561,
[email protected]; or Stephen Ripley, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
This guidance document describes one part of FDA's effort to create
a flexible regulatory approach to the oversight of genetic and genomic-
based tests. FDA held three workshops on this issue: ``Use of Databases
for Establishing the Clinical Relevance of Human Genetic Variants'' on
November 13, 2015, ``Patient and Medical Professional Perspectives on
the Return of Genetic Test Results'' on March 2, 2016, and ``Adapting
Regulatory Oversight of Next Generation Sequencing-Based Tests'' on
September 23, 2016. The goal of this effort is to help ensure patients
receive accurate and meaningful results, while promoting innovation in
test development. This guidance document describes how publicly
accessible databases of human genetic variants can serve as sources of
valid scientific evidence to support the clinical validity of genotype-
phenotype relationships in FDA's regulatory review of genetic and
genomic-based tests. FDA is also issuing a guidance entitled
``Considerations for Design, Development, and Analytical Validation of
Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs)
Intended to Aid in the Diagnosis of Suspected Germline Diseases--
Guidance for Stakeholders and Food and Drug Administration Staff,''
which is being released concurrently elsewhere in this issue of the
Federal Register.
NGS can enable rapid, broad, and deep sequencing of a portion of a
gene, entire exome(s), or a whole genome and may be used clinically for
a variety of diagnostic purposes, including risk prediction, diagnosis,
and treatment selection for a disease or condition. The rapid adoption
of NGS-based tests in both research and clinical practice is leading to
identification of an increasing number of genetic variants (e.g.,
pathogenic, benign, and of unknown significance), including rare
variants that may be unique to a single individual or family. This
guidance document describes FDA's considerations in determining whether
a genetic variant database is a source of valid scientific evidence
that could support the clinical validity of genetic and genomic based
tests. This guidance further outlines the process by which
administrators of genetic variant databases could voluntarily apply to
FDA for recognition, and how FDA would review such applications and
periodically reevaluate recognized databases. A draft guidance was
announced in the Federal Register on July 8, 2016 (81 FR 44611) and
made available for public comment. The comment period closed on October
6, 2016. FDA reviewed and considered all public comments received and
revised the guidance as appropriate.
II. Significance of Guidance
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 the ``Use of Public Human Genetic Variant
Databases to Support Clinical Validity for Genetic and Genomic-Based In
Vitro Diagnostics.'' 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.
III. Electronic Access
Persons interested in obtaining a copy of the guidance may do so by
downloading an electronic copy from the internet. A search capability
for all Center for Devices and Radiological Health guidance documents
is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. This
guidance document is also available at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm or https://www.regulations.gov. Persons unable to download
an electronic copy of ``Use of Public Human Genetic Variant Databases
to Support Clinical Validity for Genetic and Genomic-Based In Vitro
Diagnostics; Guidance for Stakeholders and Food and Drug Administration
Staff'' may send an email request to [email protected] to
receive an electronic copy of the document. Please use the document
number 16008 to identify the guidance you are requesting.
IV. Paperwork Reduction Act of 1995
This guidance refers to previously approved collections of
information. These collections of information 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
the guidance document ``Use of Public Human Genetic Variant Databases
to Support Clinical Validity for Genetic and Genomic-Based In Vitro
Diagnostics; Guidance for Stakeholders and Food and Drug Administration
Staff'' have been approved under OMB control number 0910-0850. The
collections of information in the guidance document ``Requests for
Feedback on Medical Device Submissions: The Pre-Submission Program and
Meetings with Food and Drug Administration Staff; Guidance for Industry
and Food and Drug Administration Staff'' have been approved under OMB
control number 0910-0756. The collections of information regarding
premarket submissions have been approved as follows: The collections of
information in 21 CFR part 807, subpart E, have been approved under OMB
control number
[[Page 16112]]
0910-0120 and the collections of information in 21 CFR part 814,
subparts A through E, have been approved under OMB control number 0910-
0231.
Dated: April 9, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-07686 Filed 4-12-18; 8:45 am]
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