The FDA has established human subject protection regulations addressing requirements for informed consent and Institutional Review Board (IRB) review that apply to all clinical investigations of devices involving human subjects, including deidentified human specimens.
Investigations of medical devices involving human specimens, including deidentified human specimens, are clinical investigations under the FDA’s regulations, as clarified in the FDA’s 2006 guidance, Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable, and in the final rule entitled Human Subject Protection; Acceptance of Data from Clinical Investigations for Medical Devices (see the FDA’s response to Comment 14 in the final rule 83 FR 7366).
Informed Consent Requirements
Informed consent requirements further both safety and ethical considerations by allowing potential subjects to consider both the physical and privacy risks they face if they agree to participate in a clinical trial. The FDA believes it is possible in certain circumstances for IVD device investigations to be conducted using leftover specimens, which are remnants of specimens collected for routine clinical care or analysis that would otherwise have been discarded, that were obtained without informed consent while still protecting the human subjects who are the source of such specimens. Thus, the FDA intends to exercise enforcement discretion with regard to the requirement for informed consent under the circumstances described in the FDA’s guidance, Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable.
However, this enforcement discretion does not apply to other good clinical practice (GCP) requirements, including IRB requirements under 21 CFR part 56. GCP includes review and approval by an IRB before initiating an investigation and continuing IRB review of ongoing investigations. The application of GCP helps to ensure the protections of the rights, safety, and welfare of human subjects and the quality and integrity of data from investigations using human specimens. IRB review is critical for protection of human subjects, particularly in regard to privacy and confidentiality, and the potential for use of information from the investigation for clinical patient management.
Data from Investigations Conducted Inside or Outside of the United States
The FDA's decisions are based on scientifically valid and ethically derived data. Conformance with GCP is one way to help ensure clinical data are credible, accurate, and ethically procured.
Premarket submissions supported by data from clinical investigations, including investigations involving human specimens, conducted in the United States require a statement of compliance with the GCP specified in 21 CFR parts 50, 56, and 812; or if the investigation was not conducted in compliance with those regulations, a brief statement of the reason for the noncompliance.
For premarket submissions supported by data from clinical investigations, including investigations involving human specimens, conducted outside of the United States, the submission must include information on conformance with GCP. If any such clinical investigation was not conducted in accordance with GCP, the submission must include either a waiver request or a brief statement of the reason for not conducting the investigation in accordance with GCP, and a description of steps taken to ensure that the data and results are credible and accurate and that the rights, safety, and well-being of subjects have been adequately protected. For additional information, please refer to 21 CFR 812.28 and Acceptance of Clinical Data to Support Medical Device Applications and Submissions: Frequently Asked Questions guidance.