[Federal Register Volume 90, Number 241 (Thursday, December 18, 2025)]
[Notices]
[Pages 59127-59129]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-23252]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-D-4395]
Use of Real-World Evidence To Support Regulatory Decision-Making
for Medical Devices; Guidance for Industry 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, the Agency, or we) is
announcing the availability of a final guidance entitled ``Use of Real-
World Evidence to Support Regulatory Decision-Making for Medical
Devices.'' FDA is issuing this guidance to clarify how FDA evaluates
real-world data (RWD) to determine whether they are of sufficient
quality for generating real-world evidence (RWE) that can be used in
FDA regulatory decision-making for medical devices. This final guidance
supersedes the final guidance, ``Use of Real-World Evidence to Support
Regulatory Decision-Making for Medical Devices,'' issued August 31,
2017, and provides expanded and updated recommendations.
DATES: The announcement of the guidance is published in the Federal
Register on December 18, 2025.
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-2023-D-4395 for ``Use of Real-World Evidence to Support Regulatory
Decision-Making for Medical Devices.'' 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, 240-402-7500.
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.govinfo.gov/content/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, 240-402-7500.
[[Page 59128]]
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 Real-World Evidence to Support Regulatory Decision-Making for
Medical Devices'' to the Office of Policy, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 5441, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your
request.
FOR FURTHER INFORMATION CONTACT: Soma Kalb, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 318, Silver Spring, MD 20993-0002, 301-796-6359; or
Phillip Kurs, Center for Biologics Evaluation and Research, Food and
Drug Administration, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is issuing this guidance to clarify how FDA evaluates RWD to
determine whether they are of sufficient quality for generating RWE
that can be used in FDA regulatory decision-making for medical devices.
This guidance provides expanded and updated recommendations to the 2017
guidance, ``Use of Real-World Evidence to Support Regulatory Decision-
Making for Medical Devices'' (the 2017 RWE Guidance) and supersedes the
2017 RWE Guidance. On December 29, 2022, the Food and Drug Omnibus
Reform Act of 2022 (FDORA) was signed into law as part of the
Consolidated Appropriations Act, 2023, Public Law 117-328. Section 3629
of FDORA ``Facilitating the Use of Real World Evidence'' directs FDA to
issue or revise existing guidance on considerations for the use of RWD
and RWE to support regulatory decision-making. FDA issued the draft
guidance on December 19, 2023, to propose revisions to the 2017 RWE
Guidance to satisfy the requirement under section 3629(a)(2), and is
finalizing this guidance to fulfill a commitment in section V.F. of the
Medical Device User Fee Amendments Performance Goals and Procedures,
Fiscal Years 2023 Through 2027 (MDUFA V).
This guidance includes FDA's recommendations and considerations on
the factors that sponsors should assess to demonstrate whether the RWD
are relevant and reliable for a particular regulatory decision relating
to medical devices. These recommendations and considerations apply
regardless of the RWD source and encompass processes for conducting
studies to generate RWE. FDA recognizes that there may be other
approaches to address the considerations identified in this guidance.
We encourage sponsors to discuss their approach with FDA, especially if
the approach diverges from the recommendations in this guidance.
The topics covered within this guidance are framed specifically for
the use of RWD/RWE in regulatory submissions. This guidance includes
additional clarity regarding the recommended methodologies for
collection and analysis of RWD to generate RWE, and provides updated
examples on previously used and accepted methodologies. This guidance
also provides additional clarity regarding the use of clinical data
collected from the use of a device authorized under an Emergency Use
Authorization (EUA) and describes the type of information that could be
applicable to support a determination under the Clinical Laboratory
Improvement Amendments (CLIA) (e.g., Waiver by Application).
FDA recognizes and anticipates that the Agency and industry may
need up to 60 days to perform activities to operationalize the
recommendations within this final guidance. For regulatory submissions
that will be currently pending with FDA after publication of this final
guidance, as well as those submissions received within 60 days
following publication of this final guidance, FDA generally does not
anticipate that sponsors will be ready to include the newly recommended
information outlined in this final guidance in their submission. FDA,
however, intends to review any such information if submitted at any
time.
A notice of availability of the draft guidance appeared in the
Federal Register of December 19, 2023 (88 FR 87782). FDA considered
comments received and revised the guidance as appropriate in response
to the comments, including clarifying the recommendations in the
guidance. This included clarifications on the relevance and reliability
assessment, updating examples of how RWE is used in regulatory
decision-making for medical devices, and how the relevance and
reliability assessment fits into existing benefit/risk frameworks.
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 ``Use of Real-World Evidence to Support
Regulatory Decision-Making for Medical Devices.'' 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. FDA considered the applicability
of Executive Order 14192, per OMB guidance in M-25-20, and finds this
action to be deregulatory in nature.
II. 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/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products. This guidance document is also
available at https://www.regulations.gov, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics. Persons unable to download an electronic copy of
``Use of Real-World Evidence to Support Regulatory Decision-Making for
Medical Devices'' may send an email request to [email protected] to receive an electronic copy of the document.
Please use the document number GUI01500012 and complete title to
identify the guidance you are requesting.
III. Paperwork Reduction Act of 1995
While this guidance contains no new collection of information, it
does refer to previously approved FDA collections of information. The
previously approved collections of information are subject to review by
the Office of Management and Budget (OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information
in the following table have been approved by OMB:
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21 CFR part or guidance Topic OMB control No.
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807, subpart E.................. Premarket 0910-0120
notification.
814, subparts A through E....... Premarket approval. 0910-0231
814, subpart H.................. Humanitarian Use 0910-0332
Devices;
Humanitarian
Device Exemption.
812............................. Investigational 0910-0078
Device Exemption.
860, subpart D.................. De Novo 0910-0844
classification
process.
822............................. Postmarket 0910-0449
Surveillance of
Medical Devices.
``Requests for Feedback and Q-submissions and 0910-0756
Meetings for Medical Device Early Payor
Submissions: The Q-Submission Feedback Request
Program''. Programs for
Medical Devices.
``Administrative Procedures for CLIA Administrative 0910-0607
CLIA Categorization'' and Procedures; CLIA
``Recommendations: Clinical Waivers.
Laboratory Improvement
Amendments of 1988 (CLIA)
Waiver Applications for
Manufacturers of In Vitro
Diagnostic Devices''.
800, 801, 809, and 830.......... Medical Device 0910-0485
Labeling
Regulations;
Unique Device
Identification.
803............................. Medical Device 0910-0437
Reporting.
50, 56.......................... Protection of Human 0910-0130
Subjects and
Institutional
Review Boards.
601............................. Biologics License 0910-0338
Application.
860............................. Reclassification 0910-0138
Petition for
Medical Devices.
``Emergency Use Authorization of EUA................ 0910-0595
Medical Products and Related
Authorities''.
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Lowell M. Zeta,
Acting Deputy Commissioner for Policy, Legislation, and International
Affairs.
[FR Doc. 2025-23252 Filed 12-17-25; 8:45 am]
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