Medical Devices

Acceptance of Data from Clinical Investigations for Medical Devices


In February 2018, the FDA issued a final rule on acceptance of data from clinical investigations of medical devices. The FDA updated the requirements in 21 CFR part 814 for acceptance of data from clinical investigations conducted outside the United States (OUS), and amended 21 CFR parts 807 and 812 to identify criteria for acceptance of data from clinical investigations conducted OUS as well as investigations conducted within the United States (US), which are based on the requirements in 21 CFR part 814. The final rule is intended to help ensure the quality and integrity of clinical data and the protection of human subjects.  It provides consistency in FDA’s requirements for acceptance of data from device clinical investigations, whatever the application or submission type, and whether conducted inside the US or OUS.

The FDA requires that data from clinical investigations conducted outside the US that began on or after February 21, 2019, be from investigations conducted in accordance with good clinical practice (GCP), which includes review and approval by an independent ethics committee (IEC) and informed consent from subjects. For investigations conducted in the US, the final rule requires applicants and sponsors to state whether the clinical investigation complied with 21 CFR parts 50, 56 and 812. The final rule applies to all clinical investigations that support an investigational device exemption (IDE) application, a premarket notification (510(k)) submission, a request for De Novo classification, a premarket approval (PMA) application, a humanitarian device exemption (HDE) application, or a product development protocol (PDP) application. 

The FDA guidance, "FDA Acceptance of Clinical Data to Support Medical Device Applications and Submissions Frequently Asked Questions," provides further clarification and recommendations regarding these requirements.

What is Good Clinical Practice (GCP)?

GCP is defined in 21 CFR 812.28(a)(1) as:

“a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical investigations in a way that provides assurance that the data and results are credible and accurate and that the rights, safety, and well-being of subjects are protected.” GCP includes review and approval (or provision of a favorable opinion) by an independent ethics committee (IEC) before initiating an investigation, continuing review of an ongoing investigation by an IEC, and obtaining and documenting the freely given informed consent of the subject (or a subject’s legally authorized representative, if the subject is unable to provide informed consent) before initiating an investigation. GCP does not require informed consent in life-threatening situations when the IEC reviewing the investigation finds, before initiation of the investigation, that informed consent is not feasible and either that the conditions present are consistent with those described in 21 CFR 50.23 or 50.24(a), or that the measures described in the protocol or elsewhere will protect the rights, safety, and well-being of subjects.

What to submit in an IDE or device marketing application or submission

For clinical investigations intended to support an IDE or device marketing application or submission, the following statements and information must be included for each investigation:

Investigations conducted within the US:

  • Statement that the investigation was conducted in compliance with applicable requirements in the Protection of Human Subjects regulations in 21 CFR part 50, the Institutional Review Boards regulations in 21 CFR part 56, and the Investigational Device Exemptions regulations in 21 CFR part 812; or
  • Statement describing the reasons for noncompliance.

Investigations conducted OUS:

The provisions under 21 CFR 812.28 apply.  Specifically, the following must be included for each OUS clinical investigation:

  • Statement that each investigation was conducted in accordance with GCP as described in 21 CFR 812.28(a)(1);
  • Supporting information specified under 21 CFR 812.28(b), as specified in 21 CFR 812.28(a)(2), or a cross-reference to another section of the application or submission where the information is located.

If the OUS clinical investigation did not conform to GCP, then in accordance with applicable regulations, the IDE or device marketing application or submission must include one of the following:

  • Waiver request in accordance with 21 CFR 812.28(c); or
  • Statement explaining the reason for not conducting the investigation in accordance with GCP and a description of steps taken to ensure that the data and results are credible and accurate and that the rights, safety, and well-being of subjects have been adequately protected.

Multi-site investigations conducted both inside the US and OUS:

  • Required statements and information described above, as applicable.

Note:  For In Vitro Diagnostic (IVD) applications which use leftover, de-identified human specimens, the FDA intends to continue its enforcement discretion policy regarding the requirement for informed consent under certain circumstances outlined in the FDA guidance entitled, "Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable."  When applicable, applicants may cite this policy as their reason for noncompliance with the requirement for informed consent; other requirements such as those related to IRBs still apply. 

How to request a Waiver for OUS investigations

For OUS investigations or multi-site investigations, sponsors or applicants may ask the FDA to waive any applicable requirements under 21 CFR 812.28(a)(1) and (b) by submitting a waiver request under 21 CFR 812.28(c). The FDA will decide whether to grant or deny waivers on a case-by-case basis, taking into account all appropriate circumstances.

Waiver requests may be submitted as a part of a pre-submission, an original IDE, a device marketing application or submission, a supplemental application or submission, or an amendment to an IDE or device marketing application or submission.

A cover letter should be submitted with the request indicating that a waiver under 21 CFR 812.28(c) is being requested.

Required content

A waiver request should include at least one of the following (21 CFR 812.28(c)(1)):

  • (i) An explanation why the sponsor's or applicant's compliance with the requirement is unnecessary or cannot be achieved;
    (ii) A description of an alternative submission or course of action that satisfies the purpose of the requirement; or
    (iii) Other information justifying a waiver.


Page Last Updated: 02/21/2019
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