Distinguishing Significant and Nonsignificant Risk Devices

Why is a SR or NSR Designation important?

The FDA guidance document, “Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors: Significant Risk and Nonsignificant Risk Medical Device Studies,” sheds some light on the Investigational Device Exemptions (IDE) regulations of 21 CFR 812. The IDE regulations describe significant risk (SR), nonsignificant risk (NSR), and exempt studies. For exempt studies, an institutional review board (IRB) does not determine whether the study is SR or NSR.  However, for all other studies, sponsors must make the initial risk determination of SR or NSR and present their proposed study to the IRB.  Thus, it is important that sponsors are able to distinguish significant and non-significant risk device studies. SR and NSR studies have different obligations, as explained below.


What is a Significant Risk Device Study?

According to 21 CFR 812.3(m), a SR device is an investigational device that:

  • Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
  • Is purported or represented to be for use supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
  • Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
  • Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

As a consequence of an SR designation, the sponsor must submit an IDE application to get agency approval before conducting the planned study. Then, the clinical investigators must follow 21 CFR Parts 50, 56, and 812 as they conduct the study.


What is a Nonsignificant Risk Device Study?

An NSR device study is simply one that does not meet the definition for an SR device study. As a consequence of NSR designation, the sponsor does NOT need to submit an IDE application to the FDA. However, the sponsor should provide the IRB an explanation of its determination why the study is NSR (ex: a device description, proposed investigational plan, subject selection criteria, etc.).


Differences Between SR and NSR Device Studies

To summarize, SR studies have more rigorous requirements: they must follow all of the IDE regulations in 21 CFR 812, and must have an IDE application approved by the FDA before the study. On the other hand, NSR studies need only follow the abbreviated requirements in 21 CFR 812.2(b) (addressing things like labeling, IRB approval, informed consent, monitoring, records, reports, and prohibition against promotion). NSR studies do not require an approved IDE application, and do not have to make progress reports or final reports to the FDA. The rationale is that the IRB will serve as the “FDA’s surrogate for review, approval, and continuing review of the NSR device studies.”

Check the FDA guidance linked above for examples of SR and NSR devices. Read more of our FDA posts here: FDA Tag

About the author

Amy enjoys researching and writing about developments in medical technology and how that intersects with US law. She received her J.D. from the University of Florida Levin College of Law in 2020 and now works as a Regulatory Associate for SoftwareCPR®, a general-purpose regulatory consulting firm that is recognized globally for their expertise with standards and national regulations pertaining to medical device, mobile medical app, and HealthIT software.

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