[4] Summary of the Final Rule The rule applies to data obtained from clinical investigations conducted outside the United States, inside the United States, or both outside and inside the United States that are intended to support an investigational device exemption (IDE) application, a premarket notification (510(k)) submission, a request for De Novo classification, a PMA application, a product development protocol (PDP) application, or a humanitarian device exemption (HDE).Clinical Investigations Outside the United States The final rule establishes 21 CFR § 812.28, which identifies criteria for FDA acceptance of data from clinical investigations conducted outside the United States. The criteria require the investigations to be conducted in accordance with GCPs, replacing prior PMA regulations and creating new regulations for IDE applications and other device marketing applications that previously did not address acceptance of data from clinical studies conducted outside the United States.

To this end, however, the amendments mostly affect the requirements for clinical investigations conducted OUS. As noted in FDA’s draft guidance, these amendments appear to be, in part, the result of sponsors’ increased reliance on data from clinical investigations conducted OUS.For Investigational Device Exemption (IDE) applications or premarket submissions supported by clinical data from investigations conducted OUS, the final rule adds a new provision to the IDE regulations (21 C.F.R. § 812.28) to ensure that the investigations comply with good clinical practices (GCP). This new provision states that FDA will accept data from a clinical investigation conducted OUS if the investigation is “well-designed and well-conducted” and the following information is provided:A statement that the investigation was conducted in accordance with GCP;The names of the investigators and the names and addresses of the research facilities and sites where records relating to the investigation are maintained;The investigator’s qualifications;A description of the research facility;A detailed summary of the protocol and results;Either a statement that the device used in the investigation is identical to the device that is the subject of the submission, or a detailed description of the device used in the investigation and a comparison to the device that is the subject of the submission;If the investigation is designed to support the safety and effectiveness of a device, a discussion demonstrating th

For each clinical investigation conducted in the U.S. that is used to support the request, it must include either a statement of compliance with 21 C.F.R. Parts 50, 56, and 812 or a brief statement explaining the reason for the noncompliance. For each clinical investigation conducted outside the U.S. that is used to support the request, the request must include eithera statement that the clinical investigations were conducted in accordance with good clinical practice;evidence that the clinical investigations were subject to a waiver of GCPs pursuant to 21 C.F.R. § 812.28(c);or an explanation as to why the studies did not comply with GCPs and the steps taken to ensure the data and results from the study were credible and accurate.Lastly, the final guidance checklist includes a section on the use of voluntary consensus standards. If using such standards, the request should include a declaration of conformity or an explanation of how the data support the use of the standard.