Alison Golla, Clinical Project Manager
The FDA’s final rule on Human Subject Protection; Acceptance of Data From Clinical Investigations for Medical Devices recently became effective. The final rule applies to all clinical investigations that enroll the first subject on or after February 21, 2019, and support investigational device exemptions (IDE), premarket notifications (510(k)), requests for De Novo classification, premarket approvals (PMA), product development protocols (PDP), or humanitarian device exemptions (HDE).
Purpose and Scope of Changes in Requirements
The updates provide consistency in FDA’s requirements for acceptance of clinical data for all device application and pre-market submission types, whether the investigations were conducted inside the United States (US) or outside the US (OUS). The purpose is to protect human participants and to help ensure quality and integrity of data obtained through such investigations. The FDA issued this final rule last year along with guidance providing recommendations to help sponsors and investigators understand and comply with the updated requirements. As part of the final rule, the requirements in 21 CFR 807, 812 and 814 have been amended to identify criteria for acceptance of data from studies conducted OUS, as well as within the US.
New Requirements for Acceptance of Data from US Device Clinical Investigations
For studies conducted in the US, the updates require that applicants provide:
– A statement that each investigation was conducted in compliance with FDA GCP (all applicable requirements in parts 21 CFR 50 (Protection of Human Subjects), 56 (Institutional Review Boards) and 812 (Investigational Device Exemptions).
– If the investigation was not conducted in compliance with these regulations, a brief statement of the reason(s) for noncompliance is required.
New Requirements for Acceptance of Data from OUS Device Clinical Investigations
For studies conducted OUS, the updates require that applicants provide:
– A statement that each investigation was conducted in accordance with GCP along with supporting information to demonstrate conformance with GCP. The extent of supporting information to be included is based on the risk determination as described in 21 CFR 812.28 (a)(2).
– If the investigation was not conducted in accordance with GCP, the applicant must include either:
– A waiver request in accordance with 28(c); or
– A statement explaining the reason(s) 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.
Additional information may also be required to describe the actions the sponsor or applicant has taken to ensure the research complies with GCP. This supporting information is outlined in 21 CFR 812.28(b).
Applicants may ask FDA to waive any applicable requirements by submitting a waiver request prior to or within an IDE or marketing submission or application (or as an amendment or supplement), along with an explanation as to why compliance with the requirement is unnecessary or cannot be achieved; a description of an alternative submission or course of action that satisfies the purpose of the requirement; or other information justifying a waiver as described in 21 CFR 812.28(c)1. The acceptability of a waiver will be determined on a case-by case basis.
FDA has indicated that for clinical investigations conducted OUS that do not meet the criteria, they may still accept the data from such investigations, if the agency believes that data results from a clinical investigation that is credible and accurate and that the rights, safety, and well-being of subjects have been protected.
The final rule offers regulatory flexibility for complying with the requirements for OUS, as it provides a definition of GCP but does not specify a single GCP standard that must be followed. The essential underlying FDA requirement is that data from studies involving human subjects are conducted in accordance with good clinical practice (GCP) as defined in 21 CFR 812.28(a)(1), “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…” Although a specific GCP standard is not identified, FDA has recognized ISO 14155:2011 as a GCP standard for medical device.
Through the implementation of this new final rule, FDA is requiring data from both OUS and US studies involving human subjects conform to GCP. The rule is intended to ensure the acceptance of the data by FDA and the quality and integrity of the data and protect human subjects. Further clarification and recommendations on these requirements can be found in the FDA guidance, FDA Acceptance of Clinical Data to Support Medical Device Applications and Submissions Frequently Asked Questions.
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