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Food and Drug Administration, HHS.
Notice of availability.
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.
The announcement of the guidance is published in the Federal Register on December 18, 2025.
You may submit either electronic or written comments on Agency guidances at any time as follows:
Submit electronic comments in the following way:
Submit written/paper submissions as follows:
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.
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. ( printed 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.
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.
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.
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 CDRH-Guidance@fda.hhs.gov to receive an electronic copy of the document. Please use the document number GUI01500012 and complete title to identify the guidance you are requesting.
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: ( printed page 59129)
| 21 CFR part or guidance | Topic | OMB control No. |
|---|---|---|
| 807, subpart E | Premarket notification | 0910-0120 |
| 814, subparts A through E | Premarket approval | 0910-0231 |
| 814, subpart H | Humanitarian Use Devices; Humanitarian Device Exemption | 0910-0332 |
| 812 | Investigational Device Exemption | 0910-0078 |
| 860, subpart D | De Novo classification process | 0910-0844 |
| 822 | Postmarket Surveillance of Medical Devices | 0910-0449 |
| “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program” | Q-submissions and Early Payor Feedback Request Programs for Medical Devices | 0910-0756 |
| “Administrative Procedures for CLIA Categorization” and “Recommendations: Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices” | CLIA Administrative Procedures; CLIA Waivers | 0910-0607 |
| 800, 801, 809, and 830 | Medical Device Labeling Regulations; Unique Device Identification | 0910-0485 |
| 803 | Medical Device Reporting | 0910-0437 |
| 50, 56 | Protection of Human Subjects and Institutional Review Boards | 0910-0130 |
| 601 | Biologics License Application | 0910-0338 |
| 860 | Reclassification Petition for Medical Devices | 0910-0138 |
| “Emergency Use Authorization of Medical Products and Related Authorities” | EUA | 0910-0595 |
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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