To verify exemption of a device study from Investigational Device Exemption (IDE) regulations and exemption from U.S. Food and Drug Administration (FDA) IDE approval because of nonsignificant risk (NSR) determination, the NIDCD requests the following documents:
- An official letter from the FDA specifying that the study does not require an IDE application approved by the FDA to proceed because the device study is determined to have NSR.
- Institutional review board (IRB) NSR determination must include the following documents:
- An official IRB letter specifying that the study is “approved as an NSR, presents no more than minimal risk and therefore does not require an IDE application approved by the FDA to proceed.”
- A description of the device, risk assessment, and rational for NSR provided to the IRB to facilitate the IRB’s determination.
- A letter from the Authorized Organization Representative (AOR) verifying that the NSR device study will comply with the abbreviated requirements in 21 CFR 812.2(b). These abbreviated requirements address labeling, IRB approval, informed consent, monitoring, records, reports, and prohibition against promotion. There is no need, however, to submit progress reports or final reports to the FDA.*
Please note the difference between NSR and Minimal Risk Determinations. IRBs should not confuse their responsibility to make an SR (significant risk)/NSR determination for a device study with the concept of “minimal risk.” “Minimal risk” is a term used in the IRB regulations in part to identify certain studies that IRBs may approve through an expedited review procedure. For a device study to be eligible for expedited review, it must be an NSR study AND present no more than minimal risk to the subject. (See 21 CFR 56.110.)
IRBs should not confuse their responsibility to review and approve research for conduct at a clinical site with the SR/NSR determination. IRBs make the SR/NSR determination before the IRB conducts its review of the study under Part 56. The judgment of whether a study poses a significant risk or nonsignificant risk is based on the significance of the potential harm that may result from participation in the study, including the use of the device, whereas the IRB’s decision to approve a study for implementation is based on the study’s risk-benefit assessment.*
An FDA determination of risk is final.
Additional Key Points from the FDA Guidance
Expectations for the sponsor (principal investigator, or PI):
- Sponsors are responsible for making the initial risk determination and presenting it to the IRB.*
- If the sponsor identifies a study as NSR, the sponsor must provide the reviewing IRB with an explanation of its determination (21 CFR 812.2(b)(1)(ii)) and should provide any other information that may help the IRB in evaluating the risk of the study, e.g., a description of the device, reports of prior investigations with the device, the proposed investigational plan, subject selection criteria, and other information the IRB may need.* The sponsor should provide the IRB with a risk assessment and the rationale used in making its SR or NSR determination.*
- If the FDA has determined that the study is NSR, the sponsor should so inform the IRB* to reduce the IRB’s workload and facilitate the IRB’s review.
Expectations for IRB review:
- Unless the FDA has already made a risk determination for the study, the IRB must review the sponsor's SR or NSR determination for every investigational medical device study reviewed and modify the determination if the IRB disagrees with the sponsor.*
- An IRB’s NSR determination is important because the IRB serves as the FDA’s surrogate for review, approval, and continuing review of the NSR device studies. An NSR device study may start at the institution as soon as the IRB reviews and approves the study and without prior approval by the FDA.*
- IRBs should have standard operating procedures that explain how the IRB makes SR and NSR determinations and how decisions are documented. FDA considers this determination to be part of the IRB’s responsibilities for conducting its initial review of a study. (See 21 CFR 56.108.)*
- If the IRB determines the study is NSR, the IRB may approve the study using the criteria at 21 CFR 56.111. The study may begin without submission of an IDE application to the FDA.
- The IRB should write its decision in the meeting minutes. The minutes should describe the IRB’s reason for its SR or NSR determination and may also include the documentation used to establish the IDE status for the study.*
- The FDA is available to help the IRB in making its risk determination.*