FDA Sets Rule for Use of OUS Clinical Data

The FDA has published a final rule clarifying which data the agency will accept from clinical data about medical devices collected outside the U.S. (OUS).

The final rule, published February 21, 2018, “mostly affect the requirements for clinical investigations conducted OUS. As noted in FDA’s guidance, these amendments appear to be, in part, the result of sponsors’ increased reliance on data from clinical investigations conducted OUS,” according to the FDA Law Blog published by the law firm, Hyman, Phelps & McNamara PC.

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).

GCP is defined 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.” 83 Fed. Reg. 7366, 7386 (new § 812.28(a)(1)).

According to the Law Blog, “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 that the data constitute valid scientific evidence within the meaning of 21 C.F.R. § 860.7;
• The name and address of the Independent Ethics Committee (IEC) that reviewed the investigation;
• A summary of the IEC’s decision to approve or modify and approve the investigation;
• A description of how informed consent was obtained;
• A description of any incentives provided to the subjects to participate;
• A description of how the sponsor monitored the investigation; and
• A description of how investigators were trained to comply with GCP and to conduct the investigation in accordance with the protocol.”

All IDE applications and medical device premarket submissions with OUS data must now confirm compliance with GCP, as defined in the new provision described above.

Advice for Device Makers

McKenzie E. Cato, a law clerk with the law firm, writes, “In practice, it might be a good idea too for anyone submitting a 510(k) to add a new section that would include the statement of compliance, along with whatever additional information is required under the new rule. One can imagine that FDA will eventually add this statement as another item on the 510(k) “Refuse to Accept” checklist, so a separate section will provide greater clarity that the information is there.”

Cato adds that these new provisions and FDA’s guidance, “will hopefully provide greater clarity to sponsors about how to demonstrate that clinical data collected from clinical investigations conducted OUS are adequate under FDA’s standards. However, now that the requirements are explicitly listed in FDA’s regulations, FDA will have less flexibility or discretion to accept OUS clinical data if compliance is not shown. The new regulations will also increase the burden on sponsors, who must now affirmatively produce and/or describe in their IDE applications or premarket medical device submissions the items listed above.”

To study the new rule, click here.