Document ID: FDA-2016-D-1270-0040
Agency: fda
Document Type: Notice
Title: 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
Posted Date: 2018-04-13T04:00Z

[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

[[Page 16108]]

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]
 BILLING CODE 4164-01-P