On February 25, 2013, FDA issued a proposed rule incorporating the principles of “Good Clinical Practice” (“GCP”) into the requirements for FDA acceptance of data from clinical studies conducted outside the United States, and extending such requirements to studies supporting all types of device submissions, for both U.S. and foreign studies.  Under the proposed rule, FDA may deny or withdraw approval of a PMA that relies upon foreign studies failing to comply with GCP, and may refuse to accept in support of 510(k) premarket notifications, investigational device exemptions (“IDEs”), humanitarian device exemptions (“HDEs”), or product development protocols (“PDPs”), clinical studies that fail to comply with applicable GCP requirements.

The proposed rule adds to Part 812 a definition of 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.”  Key elements of GCP include review and approval by an independent ethics committee (IEC) before initiating a study, continuing review of an ongoing study by an IEC, and obtaining and, in most situations, documenting the freely given informed consent of the subject before initiating a study.

The primary differences between the proposed rule and existing regulation are as follows: 

  • Changes to Human Subject Protection Requirements in Foreign Studies.  Current regulations allow FDA to accept foreign clinical data in support of a premarket approval application (“PMA”) in conformance with the Declaration of Helsinki or the laws and regulations of the country in which research is conducted, whichever accords greater protection to human subjects.  FDA proposes to replace this rule with a unified approach—requiring all foreign clinical studies supporting PMAs to comply with specified GCP and recordkeeping requirements. 
  • Extension of Human Subject Protection Requirements to Foreign Studies Supporting non-PMA Submissions.  Current regulations do not specify the criteria for FDA to accept foreign clinical data in support of 510(k)s, IDEs, HDEs, or PDPs.  The proposed rule would require GCP compliance for foreign studies supporting each of these submissions, to varying degrees depending on whether it is a significant risk device or a nonsignificant risk device or device study otherwise exempted under 21 CFR 812.2(c). If GCP were not met, the submission must explain what steps were taken to assure the data are accurate and how the rights of study subjects were protected. 
  • Extension of Human Subject Protection Requirements to U.S. Studies Supporting non-PMA Submissions.  Current regulations require a PMA applicant to certify that various aspects of GCPs are met for studies conducted within the U.S.  The proposed rule would extend these certification requirements to U.S. studies conducted in support of 510(k), HDE, or IDE submissions.  If GCP requirements were not met, there should be a statement explaining the reasons for noncompliance.  

The requirements in the proposed rule tend to track existing regulations for the acceptance of foreign clinical studies submitted in support of drug or biological product applications in part 312.  For example, the proposed rule requires applicants to include a statement that foreign studies were conducted in accordance with GCP, maintain and provide certain information supporting the statement, and keep records that would allow FDA to verify the accuracy of the statement. 

According to FDA, the proposed rule was spurred by the need to (1) update standards for the protection of human subjects (indeed, the current regulations refer to the 1983 version of the Declaration of Helsinki, which has been amended six times since); (2) ensure the quality and integrity of clinical data supporting submissions; (3) reduce the complexities facing investigators of multinational studies who must document the differences between the Declaration of Helsinki and the protections mandated by the host country; and (4) create consistency in human protection requirements across submissions for drugs, biologics, and different types of devices. 

Comments on the proposed rule are due by May 28, 2013.