On April 21, the US Food and Drug Administration (FDA) announced the availability of a draft guidance for industry and FDA staff entitled, “Acceptance of Medical Device Clinical Data from Studies Conducted Outside the United States.”
This draft guidance document articulates FDA’s policy of accepting scientifically valid clinical data obtained from foreign clinical studies in support of premarket submissions for devices. It focuses on considerations that sponsors of device submissions should take into account when initiating—or relying on previously collected data from—a clinical study outside the United States (OUS) to support an Investigational Device Exemption (IDE), Premarket Notification (510(k)), De Novo Petition (de novo), Humanitarian Device Exemption (HDE), or Premarket Approval Application (PMA). Currently, FDA regulations specifically address OUS studies conducted in support of PMA applications, and do not address other device submissions, such as 510(k) submissions, HDE applications, or IDE applications. FDA has issued a proposed rule which, when finalized, would require that foreign clinical studies in support of PMAs, IDEs, HDEs and 510(k)s be conducted in accordance with good clinical practice (GCP).
The guidance makes clear that FDA requires valid scientific evidence to support many device premarket applications, including 510(k)s, PMAs, and de novos. See 21 CFR 860.7. For these applications, the same standard applies to OUS data as to data from clinical trials conducted in the US. Valid scientific evidence is evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. Should FDA determine that the OUS data constitute valid scientific evidence, under 21 CFR 860.7, then the OUS data can be used to support clearance or approval of the application. The guidance encourages sponsors seeking to initiate or rely on an OUS device study to seek input from FDA at the earliest stage possible using the Pre-Submission process. It makes clear that early collaboration on the clinical trial design between the agency and the sponsor can facilitate the submission of adequate OUS data and minimize the possibility for additional or duplicative US studies.
The guidance also notes other important considerations to take into account when initiating or relying on OUS data. These considerations include differences between the US and OUS standards with regard to clinical conditions, study populations, and regulatory requirements. The guidance provides several examples of issues that may arise when using clinical data from device studies conducted OUS to support FDA regulatory decisions, how FDA and sponsors may seek to resolve such issues, and the likely review outcomes.