[Federal Register Volume 83, Number 72 (Friday, April 13, 2018)]
[Notices]
[Pages 16106-16108]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-07687]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-D-1270]
Considerations for Design, Development, and Analytical Validation
of Next Generation Sequencing-Based In Vitro Diagnostics Intended To
Aid in the Diagnosis of Suspected Germline Diseases; 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 ``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.'' FDA's vision is that NGS-
based tests can be developed, validated, and offered for clinical use
through a process that leverages appropriate standards, quality systems
controls, and community assessment of clinical validity to streamline
the premarket review process. This guidance provides recommendations
for designing, developing, and establishing analytical performance for
NGS-based tests used for whole exome human DNA sequencing (WES) or
targeted human DNA sequencing intended to aid in the diagnosis of
symptomatic individuals with suspected germline diseases or other
conditions. These recommendations are based on FDA's understanding of
the tools and processes needed to run an NGS-based test along with the
design and analytical validation considerations appropriate for such
tests.
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-1270 for ``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.'' 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
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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.
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
``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'' 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: Zivana Tezak, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4544, Silver Spring, MD 20993-0002, 301-796-6206;
or [email protected]; or Adam Berger, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4547, Silver Spring, MD 20993-0002, 240-402-1592;
or [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
FDA is committed to implementing a flexible and adaptive regulatory
approach to the oversight of NGS-based tests, which will foster
innovation and simultaneously assure that patients have access to
accurate and meaningful test results. FDA held two public workshops on
this issue: ``Optimizing FDA's Regulatory Oversight of Next Generation
Sequencing Diagnostic Tests Public Workshop'' held on February 20,
2015, and ``Standards Based Approach to Analytical Performance
Evaluation of Next Generation Sequencing In Vitro Diagnostic Tests''
held on November 12, 2016.
This guidance document provides recommendations for designing,
developing, and establishing analytical validity of NGS-based tests
used for WES or targeted human DNA sequencing intended to aid in the
diagnosis of individuals with suspected germline diseases or other
conditions (hereinafter referred to as ``NGS-based tests for germline
diseases'' or ``NGS-based tests''). It also outlines considerations for
possibly classifying certain NGS-based tests for germline diseases in
class II and exempting them from premarket notification requirements.
These recommendations should be used as guidelines for test developers
for premarket submissions. However, the longer term goal is for these
recommendations to form the basis for standards that FDA could
recognize or for special controls and/or conditions for premarket
notification (510(k)) exemption. FDA is also issuing a guidance
entitled ``Use of Public Human Genetic Variant Databases to Support
Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics''
which is being issued concurrently elsewhere in this issue of the
Federal Register.
On July 8, 2016, FDA announced a draft guidance in the Federal
Register (81 FR 44614) 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 considerations for design, development, and
analytical validation of NGS-based IVDs used to aid in the diagnosis of
suspected germline diseases. 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 https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. This
guidance document is also available at https://www.regulations.gov.
Persons unable to download an electronic copy of ``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'' may send an email request to
[email protected] to receive an electronic copy of the
document. Please use the document number 16009 to identify the guidance
you are requesting.
IV. Paperwork Reduction Act of 1995
This guidance refers to previously approved collections of
information found in FDA regulations. 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 21 CFR part 807, subpart E, regarding
premarket notification submissions, have been approved under OMB
control number 0910-0120; the collections of information in 21 CFR part
801 and 21 CFR 809.10, regarding labeling, have been approved under OMB
control
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number 0910-0485; the collections of information in 21 CFR part 814,
subparts A through E, regarding premarket approval, have been approved
under OMB control number 0910-0231; the collections of information in
21 CFR part 820, regarding the quality system regulation, have been
approved under OMB control number 0910-0073; and 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'' have been approved under OMB control
number 0910-0756.
Dated: April 9, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-07687 Filed 4-12-18; 8:45 am]
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