On February 25, 2013, the FDA proposed new regulations to amend its current requirements on the acceptance of clinical data for medical devices.  Specifically, the FDA is proposing to amend its acceptance criteria for data from clinical studies outside of the United States used as support for an investigational device exemption (IDE) application, a premarket notification (510k) submission, a premarket approval (PMA) application, a product development protocol (PDP), or a humanitarian device exemption (HDE) application, by requiring that such studies be conducted in accordance with good clinical practice (GCP) standards.  In addition, the proposed rule seeks to amend the 510(k), HDE, and IDE requirements for FDA acceptance of data from clinical studies conducted inside the United States to parallel existing FDA requirements for PMA applications.  Should these proposed requirements ultimately become final, medical device manufacturers will need to ensure that their clinical research policies and procedures meet these new requirements to ensure that data from clinical studies used to support FDA regulatory applications and submissions will be accepted by the FDA.

A copy of the proposed rule, “Human Subject Protection; Acceptance of Data From Clinical Studies for Medical Devices,” 78 Fed. Reg. 12665 (Feb. 25th, 2013), is available here.

FDA Acceptance of Data from Non-U.S. Clinical Studies

Currently, clinical studies conducted outside the United States submitted  in support of a PMA application and conducted under an IDE  must comply with 21 C.F.R. Part 812.  However, even if the study is not conducted under an IDE, the FDA will accept a study submitted in support of a PMA that has been conducted outside the United States if the data are valid and the investigator has conducted the study in conformance with the Declaration of Helsinki or the laws and regulations of the country in which the research is conducted, whichever accords greater protection to the human subjects.  If the standards of the country are used, the applicant must state in detail any differences between those standards and the Declaration of Helsinki and explain why they offer greater protection to the human subjects.

There is no equivalent requirement for 510(k) submissions, HDE applications, and IDE applications.  Regulations for 510(k) submissions and IDE and HDE applications do not address requirements for FDA acceptance of data from non-U.S. clinical studies.

To help ensure the integrity of data and the protection of human subjects, and to help provide consistency across its regulations, under the proposed rule, the FDA is proposing to require compliance with GCP in order for the FDA to accept data from clinical studies conducted outside the United States to support a PMA application, a 510(k) submission, HDE application, or an IDE application. The FDA is proposing to define GCP as “a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials in a way that provides assurance that the data and reported results are credible and accurate and that the rights, safety, and well-being of trial subjects are protected.”  GCP includes approval and on-going review of the study by an independent ethics committee, as well as obtaining and documenting informed consent.  As part of the submission or application, FDA would require a statement that the study was conducted in accordance with GCP, as well as a description of the actions that were taken to ensure that the study conformed to GCP standards.  If the study was not conducted in accordance with GCP, then a brief statement would need to be provided to explain why the study was not conducted in accordance with GCP, as well as a description of the steps taken to assure that the data and reported results are credible and accurate and that the welfare of the study subjects was protected.  FDA would also require a statement assuring the availability of the data from the study to FDA for validation through an onsite inspection or other appropriate means.

Consistency of FDA Regulations on Data Acceptance for U.S. Studies

Under the FDA’s current regulations, as part of a PMA submission, the applicant must certify that each U.S. study used in support of the application was in compliance with FDA requirements in 21 C.F.R. Part 50 (Informed Consent Requirements), C.F.R. Part 56 (IRB Requirements) and Part 812 (IDE Requirements), and if a study was not conducted in compliance with these regulations, then the application must provide a statement explaining the reason for noncompliance.  However, currently, there is no equivalent FDA regulatory compliance requirement under the current 510(k), HDE, and IDE regulations.  These regulations do not address the requirements for FDA acceptance of data from U.S. clinical studies.

In order to provide consistency in the FDA’s acceptance criteria for clinical data, under the proposed rule, the FDA proposes to require the same certifications and statements for 510(k) submissions and IDE and HDE applications that are currently required in PMA submissions.  That is, 510(k) submissions, IDE applications, and HDE applications that contain clinical data from a U.S. clinical study would require a statement that each study was conducted in compliance with applicable human subjects regulations in 21 C.F.R. Part 50, the IRB regulations in 21 C.F.R. Part 56, and the IDE regulations in Part 812, or otherwise provide a statement why the study was not in compliance.