83 FR 16110 - 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

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 72 (April 13, 2018)

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.

[Federal Register Volume 83, Number 72 (Friday, April 13, 2018)]
[Notices]
[Pages 16110-16112]
From the Federal Register Online  [www.thefederalregister.org]
[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.thefederalregister.org/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]
 BILLING CODE 4164-01-P