83 FR 16106 - 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
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 72 (April 13, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 72 (April 13, 2018)
| Page Range | 16106-16108 | |
| FR Document | 2018-07687 |
[Federal Register Volume 83, Number 72 (Friday, April 13, 2018)] [Notices] [Pages 16106-16108] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-07687] ----------------------------------------------------------------------- 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. ----------------------------------------------------------------------- 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 [[Page 16107]] 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. 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
![16106 Federal Register / Vol. 83, No. 72 / Friday, April 13, 2018 / Notices
appropriate advisory committee meeting DEPARTMENT OF HEALTH AND www.regulations.gov will be posted to
link. HUMAN SERVICES the docket unchanged. Because your
Procedure: Interested persons may comment will be made public, you are
Food and Drug Administration solely responsible for ensuring that your
present data, information, or views,
orally or in writing, on issues pending [Docket No. FDA–2016–D–1270] comment does not include any
before the committee. All electronic and confidential information that you or a
written submissions submitted to the Considerations for Design, third party may not wish to be posted,
Development, and Analytical Validation such as medical information, your or
Docket (see the ADDRESSES section) on
of Next Generation Sequencing-Based anyone else’s Social Security number, or
or before April 26, 2018, will be
In Vitro Diagnostics Intended To Aid in confidential business information, such
provided to the committee. Oral
the Diagnosis of Suspected Germline as a manufacturing process. Please note
presentations from the public will be
Diseases; Guidance for Stakeholders that if you include your name, contact
scheduled between approximately 1:15
and Food and Drug Administration information, or other information that
p.m. and 2:15 p.m. Those individuals identifies you in the body of your
interested in making formal oral Staff; Availability
comments, that information will be
presentations should notify the contact AGENCY: Food and Drug Administration, posted on https://www.regulations.gov.
person and submit a brief statement of HHS. • If you want to submit a comment
the general nature of the evidence or ACTION: Notice of availability. with confidential information that you
arguments they wish to present, the do not wish to be made available to the
names and addresses of proposed SUMMARY: The Food and Drug
public, submit the comment as a
participants, and an indication of the Administration (FDA or Agency) is
written/paper submission and in the
approximate time requested to make announcing the availability of the final
manner detailed (see ‘‘Written/Paper
their presentation on or before April 24, guidance entitled ‘‘Considerations for
Submissions’’ and ‘‘Instructions’’).
2018. Time allotted for each Design, Development, and Analytical
presentation may be limited. If the Validation of Next Generation Written/Paper Submissions
number of registrants requesting to Sequencing (NGS)-Based In Vitro Submit written/paper submissions as
speak is greater than can be reasonably Diagnostics (IVDs) Intended to Aid in follows:
accommodated during the scheduled the Diagnosis of Suspected Germline • Mail/Hand delivery/Courier (for
open public hearing session, FDA may Diseases; Guidance for Stakeholders and written/paper submissions): Dockets
conduct a lottery to determine the Food and Drug Administration Staff.’’ Management Staff (HFA–305), Food and
speakers for the scheduled open public FDA’s vision is that NGS-based tests can Drug Administration, 5630 Fishers
hearing session. The contact person will be developed, validated, and offered for Lane, Rm. 1061, Rockville, MD 20852.
notify interested persons regarding their clinical use through a process that • For written/paper comments
request to speak by April 25, 2018. leverages appropriate standards, quality submitted to the Dockets Management
systems controls, and community Staff, FDA will post your comment, as
Persons attending FDAs advisory assessment of clinical validity to well as any attachments, except for
committee meetings are advised that streamline the premarket review information submitted, marked and
FDA is not responsible for providing process. This guidance provides identified, as confidential, if submitted
access to electrical outlets. recommendations for designing, as detailed in ‘‘Instructions.’’
For press inquiries, please contact the developing, and establishing analytical Instructions: All submissions received
Office of Media Affairs at fdaoma@ performance for NGS-based tests used must include the Docket No. FDA–
fda.hhs.gov or 301–796–4540. for whole exome human DNA 2016–D–1270 for ‘‘Considerations for
FDA welcomes the attendance of the sequencing (WES) or targeted human Design, Development, and Analytical
public at its advisory committee DNA sequencing intended to aid in the Validation of Next Generation
meetings and will make every effort to diagnosis of symptomatic individuals Sequencing (NGS)-Based In Vitro
accommodate persons with disabilities. with suspected germline diseases or Diagnostics (IVDs) Intended to Aid in
If you require accommodations due to a other conditions. These the Diagnosis of Suspected Germline
disability, please contact Cindy Chee recommendations are based on FDA’s Diseases; Guidance for Stakeholders and
(see FOR FURTHER INFORMATION CONTACT) understanding of the tools and Food and Drug Administration Staff.’’
at least 7 days in advance of the processes needed to run an NGS-based Received comments will be placed in
meeting. test along with the design and analytical the docket and, except for those
validation considerations appropriate submitted as ‘‘Confidential
FDA is committed to the orderly for such tests. Submissions,’’ publicly viewable at
conduct of its advisory committee https://www.regulations.gov or at the
DATES: The announcement of the
meetings. Please visit our website at Dockets Management Staff between 9
guidance is published in the Federal
https://www.fda.gov/Advisory a.m. and 4 p.m., Monday through
Register on April 13, 2018.
Committees/AboutAdvisoryCommittees/ Friday.
ADDRESSES: You may submit either
ucm111462.htm for procedures on • Confidential Submissions—To
public conduct during advisory electronic or written comments on
Agency guidances at any time as submit a comment with confidential
committee meetings. information that you do not wish to be
follows:
Notice of this meeting is given under made publicly available, submit your
the Federal Advisory Committee Act (5 Electronic Submissions comments only as a written/paper
daltland on DSKBBV9HB2PROD with NOTICES
U.S.C. app. 2). Submit electronic comments in the submission. You should submit two
Dated: April 10, 2018. following way: copies total. One copy will include the
• Federal eRulemaking Portal: information you claim to be confidential
Leslie Kux,
https://www.regulations.gov. Follow the with a heading or cover note that states
Associate Commissioner for Policy. instructions for submitting comments. ‘‘THIS DOCUMENT CONTAINS
[FR Doc. 2018–07747 Filed 4–12–18; 8:45 am] Comments submitted electronically, CONFIDENTIAL INFORMATION.’’ The
BILLING CODE 4164–01–P including attachments, to https:// Agency will review this copy, including
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number 0910–0485; the collections of electronic filing system will accept Dockets Management Staff between 9
information in 21 CFR part 814, comments until midnight Eastern Time a.m. and 4 p.m., Monday through
subparts A through E, regarding at the end of June 12, 2018. Comments Friday.
premarket approval, have been received by mail/hand delivery/courier • Confidential Submissions—To
approved under OMB control number (for written/paper submissions) will be submit a comment with confidential
0910–0231; the collections of considered timely if they are information that you do not wish to be
information in 21 CFR part 820, postmarked or the delivery service made publicly available, submit your
regarding the quality system regulation, acceptance receipt is on or before that comments only as a written/paper
have been approved under OMB control date. submission. You should submit two
number 0910–0073; and the collections copies total. One copy will include the
Electronic Submissions information you claim to be confidential
of information in the guidance
document ‘‘Requests for Feedback on Submit electronic comments in the with a heading or cover note that states
Medical Device Submissions: The Pre- following way: ‘‘THIS DOCUMENT CONTAINS
Submission Program and Meetings with • Federal eRulemaking Portal: CONFIDENTIAL INFORMATION.’’ The
Food and Drug Administration Staff’’ https://www.regulations.gov. Follow the Agency will review this copy, including
have been approved under OMB control instructions for submitting comments. the claimed confidential information, in
number 0910–0756. Comments submitted electronically, its consideration of comments. The
including attachments, to https:// second copy, which will have the
Dated: April 9, 2018.
www.regulations.gov will be posted to claimed confidential information
Leslie Kux, the docket unchanged. Because your redacted/blacked out, will be available
Associate Commissioner for Policy. comment will be made public, you are for public viewing and posted on
[FR Doc. 2018–07687 Filed 4–12–18; 8:45 am] solely responsible for ensuring that your https://www.regulations.gov. Submit
BILLING CODE 4164–01–P comment does not include any both copies to the Dockets Management
confidential information that you or a Staff. If you do not wish your name and
third party may not wish to be posted, contact information to be made publicly
DEPARTMENT OF HEALTH AND such as medical information, your or available, you can provide this
HUMAN SERVICES anyone else’s Social Security number, or information on the cover sheet and not
confidential business information, such in the body of your comments and you
Food and Drug Administration as a manufacturing process. Please note must identify this information as
[Docket No. FDA–2018–N–1111] that if you include your name, contact ‘‘confidential.’’ Any information marked
information, or other information that as ‘‘confidential’’ will not be disclosed
Agency Information Collection identifies you in the body of your except in accordance with 21 CFR 10.20
Activities; Proposed Collection; comments, that information will be and other applicable disclosure law. For
Comment Request; Permanent posted on https://www.regulations.gov. more information about FDA’s posting
Discontinuation or Interruption in • If you want to submit a comment of comments to public dockets, see 80
Manufacturing of Certain Drug and with confidential information that you FR 56469, September 18, 2015, or access
Biological Products do not wish to be made available to the the information at: https://www.gpo.gov/
public, submit the comment as a fdsys/pkg/FR-2015-09-18/pdf/2015-
AGENCY: Food and Drug Administration,
written/paper submission and in the 23389.pdf.
HHS.
manner detailed (see ‘‘Written/Paper Docket: For access to the docket to
ACTION: Notice. Submissions’’ and ‘‘Instructions’’). read background documents or the
SUMMARY: The Food and Drug Written/Paper Submissions electronic and written/paper comments
Administration (FDA or Agency) is received, go to https://
Submit written/paper submissions as www.regulations.gov and insert the
announcing an opportunity for public
follows: docket number, found in brackets in the
comment on the proposed collection of • Mail/Hand delivery/Courier (for
certain information by the Agency. heading of this document, into the
written/paper submissions): Dockets ‘‘Search’’ box and follow the prompts
Under the Paperwork Reduction Act of Management Staff (HFA–305), Food and
1995 (PRA), Federal Agencies are and/or go to the Dockets Management
Drug Administration, 5630 Fishers Staff, 5630 Fishers Lane, Rm. 1061,
required to publish notice in the Lane, Rm. 1061, Rockville, MD 20852.
Federal Register concerning each Rockville, MD 20852.
• For written/paper comments
proposed collection of information, FOR FURTHER INFORMATION CONTACT:
submitted to the Dockets Management
including each proposed extension of an Staff, FDA will post your comment, as Domini Bean, Office of Operations,
existing collection of information, and well as any attachments, except for Food and Drug Administration, Three
to allow 60 days for public comment in information submitted, marked and White Flint North, 10A–12M, 11601
response to the notice. This notice identified, as confidential, if submitted Landsdown St., North Bethesda, MD
solicits comments on ‘‘Permanent as detailed in ‘‘Instructions.’’ 20852, 301–796–5733, PRAStaff@
Discontinuation or Interruption in Instructions: All submissions received fda.hhs.gov.
Manufacturing of Certain Drug and must include the Docket No. FDA– SUPPLEMENTARY INFORMATION: Under the
Biological Products.’’ 2018–N–1111 for ‘‘Permanent PRA (44 U.S.C. 3501–3520), Federal
DATES: Submit either electronic or Discontinuation or Interruption in Agencies must obtain approval from the
written comments on the collection of Manufacturing of Certain Drug and Office of Management and Budget
daltland on DSKBBV9HB2PROD with NOTICES
information by June 12, 2018. Biological Products.’’ Received (OMB) for each collection of
ADDRESSES: You may submit comments comments, those filed in a timely information they conduct or sponsor.
as follows. Please note that late, manner (see ADDRESSES), will be placed ‘‘Collection of information’’ is defined
untimely filed comments will not be in the docket and, except for those in 44 U.S.C. 3502(3) and 5 CFR
considered. Electronic comments must submitted as ‘‘Confidential 1320.3(c) and includes Agency requests
be submitted on or before June 12, 2018. Submissions,’’ publicly viewable at or requirements that members of the
The https://www.regulations.gov https://www.regulations.gov or at the public submit reports, keep records, or
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Document Created: 2018-04-13 00:18:15
Document Modified: 2018-04-13 00:18:15
| 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 | The announcement of the guidance is published in the Federal Register on April 13, 2018. | |
| 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. | |
| FR Citation | 83 FR 16106 |
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