The article provides a brief overview of the regulatory requirements related to various studies medical devices could be subject to. 

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to significant risk and nonsignificant risk medical device studies. The document provides additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered by clinical investigators, study sponsors, and other parties involved. At the same time, it is important to mention that FDA guidance documents are non-binding, and are not intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with existing legislation and has been agreed with the authority in advance. 


Regulatory Background 

As it is stated by the FDA, this guidance is intended to provide advice to sponsors, clinical investigators, and institutional review boards (IRBs) on how to determine the difference between significant risk and nonsignificant risk medical device studies. The present document constitutes an updated and revised version of the guidance issued by the FDA earlier in 1998. In particular, the new version includes examples of both significant and nonsignificant risk devices to better illustrate the approach to be applied in terms of risk determination. 

By the Investigational Device Exemptions (IDE) regulation (21 CFR 812), there are three types of device studies:

  • Significant risk (SR),
  • Nonsignificant risk (NSR), and 
  • Exempt studies.

The present guidance describes in detail the regulatory matters related to the first two types of studies, while the third one is addressed separately in another guidance. 

First of all, the authority provides definitions to be applied when determining the significance of risk associated with the medical device in question. According to the aforementioned regulation, an SR device stands for 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 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. 

An NSR device study is not related to the device described herein above. 

Determination and Key Differences 

As further explained by the FDA, the initial determination of risk should be conducted by a sponsor — a party responsible for a medical device study — and then presented to the IRB. At the same time, the authority may also advise and suggest determination it finds appropriate. 

The IRB may review the study in question and make changes to risk determination unless such determination is already made by the FDA since the determination made by the latter is considered final and non-negotiable. The authority may also assist IRB in making the risk determination. The FDA makes its determination when the IDE is submitted by the interested party, or there is a request for determination submitted by the sponsor. 

The document further outlines the key differences between the two types of risk determinations. According to the guidance, SR device studies should be in line with the regulatory requirements set forth by 21 CFR 812, and also require an IDE application to be approved by the authority before the commencement of a study. 

At the same time, NSR device studies are subject to regulatory requirements set forth by 21 CFR 812.2(b) in terms of labeling, IRB approval, informed consent, monitoring, records, reports, and the prohibition against promotion. For this type of study, there is no need for an FDA-approved IDE application, nor sponsors or IRBs are obliged to report approval to the authority. For NSR studies, the IRB determination becomes especially important since in this case the FDA is not involved — as it is stated in the guidance, an NSR device study may start at the institution as soon as the IRB reviews and approves the study and without prior approval obey FDA. 


Sponsor’s Responsibilities 

The guidance also describes in detail the aspects related to the responsibilities of study sponsors in the context of different types of studies. For instance, in the case of an NSR device study, a sponsor shall: 

  • Justify the determination made and provide additional information addressing the risk-related matters for the IRB to be able to validate the correctness of the determination. The information to be submitted may include but is not limited to the description of the device, reports of prior investigations, the proposed investigational plan, etc. 
  • Notify the IRB in case an NSR determination is made by the FDA. This will reduce the workload of the IRB and streamline the process in general. 

In the case of an SR device study, responsibilities will be slightly different. In particular, the sponsor:

  • We will have to submit an IDE application to be approved by the authority;
  • Must advise its clinical investigators about the SR status and obtain their agreement to comply with the applicable regulations governing such studies; and
  • Apply for review by the IRB before the initial IDE application will be approved by the authority. Nevertheless, as was mentioned before, the study itself can be commenced only once the IDE application is approved by the FDA. 

In summary, the present FDA guidance provides an overview of the regulatory requirements for different types of clinical studies based on the risk associated thereto. The document explains the approach to be applied when determining the risk, and also describes the steps to be taken by the parties involved to streamline the process. 



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