We recommend that you begin with the exemptions in 21 CFR 812.2(c). Your proposed IVD study is exempt from most provisions of the IDE regulation if it fits any one of the following three categories:
- The IVD is a pre-amendments device (i.e., a device that was in commercial distribution prior to the enactment of the 1976 Medical Device Amendments to the Act), other than a transitional device, and is used or investigated according to the indications in the labeling at that time.
- The IVD is a device, other than a transitional device, that has been found to be substantially equivalent to a pre-amendments device and is used or investigated according to the indications in the labeling reviewed by FDA in determining substantial equivalence.
- The IVD
• is properly labeled in accordance with 21 CFR 809.10(c);
• is noninvasive
• does not require an invasive sampling procedure that presents significant risk
• does not by design or intention introduce energy into a subject; and
• is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
For your study to be exempt from most of the requirements of the IDE regulation under this third category, it must meet all of the conditions listed in “c” above. (See also the decision tree in Appendix 1.) You should refer to 21 CFR Parts 50 and 56 for applicable requirements relating to IRBs and informed consent, including for device studies that meet the criteria described in 21 CFR 812.2(c). Additionally, investigators for those studies are still subject to 21 CFR 812.119 (the provision entitled “Disqualification of a clinical investigator.”) If your proposed study does not fit into one of the three categories listed above, you, the sponsor, must have an approved IDE (21 CFR 812.2) before you may begin your investigation, including any shipment of your investigational IVD. (Note: A device that is approved under a premarket approval application (PMA) or cleared under a 510(k) and then used in a study in accordance with the approved or cleared labeling is not investigational and, therefore, is not subject to the IDE regulation.) The requirements for an IDE depend on the level of risk that the study presents to subjects.
For a significant risk device, the sponsor must apply to FDA for an IDE approval (see 21 CFR 812.1, 812.20). For a non-significant risk device, the sponsor must meet the abbreviated requirements of 21 CFR 812.2(b), including review and approval of the investigation by an institutional review board (IRB) and compliance with informed consent requirements. A nonsignificant risk study is considered to have an approved IDE when the abbreviated requirements are met.
Note: The requirements of the “Protection of Human Subjects” and “Institutional Review Boards” regulations (21 CFR Parts 50 and 56) apply to all clinical investigations regulated by FDA under section 520(g) of the Act, as well as other clinical investigations that support applications for research or marketing permits. (21 CFR 50.1, 56.101; see also Section V, Human Subject Protection, of this guidance.) Therefore, all studies of investigational IVDs that will support applications to FDA are subject to 21 CFR Parts 50 and 56, even if they are not subject to most requirements of 21 CFR Part 812.
