The US Investigational Device Exemption Regulation (21 CFR 812)
Part 3 - Differences between Exempt and Non-Significant Risk Investigations
This is Part 3 of our series on the US Investigational Device Exemption Regulation, 21 CFR 812, governing investigational medical device studies.
In the US, investigational medical device studies fall into three different regulatory categories depending on the level of risk they pose to participants (exempt , non-significant risk (NSR) , or significant risk (SR) investigation). One area of confusion is identifying whether a clinical investigation is exempt or NSR.
An investigational device study is exempt from FDA regulations under certain conditions outlined in 21 CFR 812.2(c). These typically include:
Studies involving devices that are legally marketed (i.e. FDA approved, cleared or registered) used in accordance with their approved labeling (i.e., not for new indications).
Certain diagnostic devices that are noninvasive (e.g. IVDs), do not require invasive sampling, and do not introduce significant risk to patients. For example, the use of previously collected patient samples for retrospective testing of an IVD typically would be considered an exempt study.
Custom devices used for a unique patient where no clinical investigation is intended for broader study.
In an exempt investigation, there is no requirement for the study sponsor to comply with investigational device regulations beyond basic requirements for clinical research.
A non-significant risk (NSR) investigation involves a medical device that poses less risk to patients compared to a significant risk (SR) device but is not exempt from all regulations. For an NSR device, the abbreviated IDE regulations under 21 CFR 812.2(b) need to be followed.
The main difference between an exempt study and an NSR study is that an exempt study poses NO risk to patients as a consequence of inaccurate investigational test results. An NSR study poses SOME but MINIMAL risk to patients as a consequence of inaccurate investigational test results.
Determining whether a study is SR or NSR is the job of the IRB, but the IRB is influenced by the study sponsor’s determination. The IRB may request a determination by FDA.
In Part 4, we will discuss the differences between NSR and SR investigations.