FDA requires an IDE for Significant Risk (SR) device studies, while Non-Significant Risk (NSR) devices need only IRB approval, and some low-risk studies are exempt. Knowing your device’s risk category is key to compliance and trial success.
A key early question for sponsors is “Do I need to submit an IDE to the FDA for this clinical study, or not?” The answer depends on the device’s risk category and whether the study falls under any IDE exemption. FDA regulations break device trials into three categories: Significant Risk (SR), Non-Significant Risk (NSR), and Exempt studies. Here’s how to navigate these categories:
According to FDA information sheets, a Significant Risk device is one that presents a potential for serious risk to the health or safety of subjects. Examples include implants, devices that support or sustain human life, or those that otherwise pose a serious risk. In contrast, a Non-Significant Risk device is one that does not meet the SR criteria – FDA gives examples like most daily-wear contact lenses, diagnostic ultrasounds, or Foley catheters. The distinction is crucial because it determines the approval process: – Significant Risk (SR) studies require an IDE submission to FDA and FDA approval prior to starting the trial. They also require Institutional Review Board (IRB) approval at each site. Essentially, SR = FDA + IRB oversight. – Non-Significant Risk (NSR) studies do not require an IDE application to FDA. Instead, they only need IRB approval before starting. An NSR device study is considered to have an “approved IDE” once the IRB approves it, with the IRB serving as the primary regulator for the study. Sponsors must still follow abbreviated IDE requirements (labeling, informed consent, monitoring, records & reports) for NSR investigations, but they skip the step of obtaining FDA’s explicit IDE approval.
Certain low-risk device research is outright exempt from IDE regulations (no IDE and sometimes no IRB needed, though IRB review is often still prudent). FDA’s IDE rules (21 CFR 812.2(c)) list categories of exempt investigations, including:
If a study is exempt, no IDE submission is required to FDA. Sponsors should still ensure compliance with any other applicable regulations (often IRB and informed consent may still apply, depending on the nature of the study).
The initial determination of risk is made by the sponsor in the study planning phase. The sponsor should evaluate the device and protocol and categorize it as SR or NSR. When an IRB reviews the study, it must agree with the sponsor’s risk assessment. If the IRB disagrees and believes the device is SR when the sponsor thought it was NSR, the sponsor must notify FDA within 5 working days and the study cannot proceed without an IDE. FDA is the final arbiter: it can also be consulted directly if the risk status is unclear. Sponsors can submit a “Study Risk Determination” Q-Submission to the FDA to get an official ruling on SR/NSR status. This is a pre-submission request where FDA will review a synopsis of the device and protocol and issue a letter stating whether the study is SR, NSR, or exempt.
If FDA (or IRB) deems the study Significant Risk, an IDE application must be filed with FDA and the study cannot begin until FDA approves the IDE and the IRB approves the study.
To illustrate, consider a new implantable cardiac device – this clearly poses significant risk (implant = potential serious risk), so an IDE and FDA approval are required. On the other hand, a study using a cleared blood glucose meter in a slightly new way might be NSR or even exempt, needing only IRB review. Diagnostic device trials often fall in a gray area: if the test involves blood draws or is used to make medical decisions, it may be SR; but if it’s noninvasive and confirmatory diagnostics are in place, it could be NSR or exempt.
Always document your risk determination rationale. If there’s any uncertainty, engage the IRB early or use FDA’s Q-Submission program for a formal decision. Misjudging risk (calling an SR device “NSR” in error) can lead to compliance violations and trial delays. FDA tends to err on the side of caution – when in doubt, they may consider a device SR. So, when planning a U.S. trial, carefully assess the risk category to know if an IDE submission is mandated. This ensures you meet all regulatory obligations before enrolling patients.
