The new article describes the responsibilities of institutional review boards (IRBs) when assessing clinical studies related to medical devices, as well as the approach to be applied when determining the regulatory status of such studies based on the risks associated thereto. 

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 (SR) and non-significant risk (NSR) medical device studies. The document describes the approach to be applied for risk determination for clinical studies. The guidance provides additional clarifications based on the applicable regulatory requirements, as well as recommendations to be considered by all the parties involved to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are 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. 

The scope of the guidance covers, inter alia, the responsibilities of institutional review boards, and the approach they should apply when reviewing the clinical studies related to medical devices. 


Responsibilities: Key Points 

According to the guidance, institutional review boards:

  • Should have standard operating procedures that explain how the IRB makes SR and NSR determinations and that the decision should be documented (the FDA considers this determination to be part of the IRB’s responsibilities for conducting its initial review of a study).
  • Should make the aforementioned determination based on the information provided, including the description of a medical device subject to review, reports of prior investigations the product has been subject to, as well as the investigation plan proposed by a study sponsor and subject selection criteria to be applied. In this respect, the authority also mentions that the study sponsor as a party responsible for the study should provide the institutional review board with its risk assessment, as well as justification of the determination it makes; while an IRB may either agree with the determination made by the sponsor or disagree with it. 
  • May approve the study, should according to the IRB’s determination the study in question be considered NSR. In such a case, a study could be commenced without applying for the approval of the FDA. 
  • Inform all the parties involved in case of disagreement with the NSR determination made by the sponsor. 
  • May approve the study in question as an SR one, however, in such a case, the study cannot be commenced without the approval of the FDA. 
  • May ask a sponsor to provide additional confirmation demonstrating that there is a corresponding IDE application already approved by the FDA? 
  • Should duly document all the determinations regarding the regulatory status of clinical studies. 

Main Considerations 

The guidance further outlines the most important aspects to be taken into consideration by an institutional review board when making its determination on whether the study subject to review should be considered SR or NSR. According to the guidance, the aspects to be considered include, inter alia, the following ones:

  • The basis of risk determination should be not a device itself, but the way it is supposed to be used as per the claims made by the manufacturer. 
  • The harm that could potentially be caused due to the use of the device in question. Should it be serious, a study should be considered SR. 
  • Whether any additional procedure is to be conducted over the study subject (as well as the risks associated with such procedures and harm that could potentially be caused). 

For the last point, the document provides additional examples to illustrate the approach to be applied. 

  1. If due to the use of the device a study participant will be exposed to additional risks, including the cases when the device is intended to support or sustain human life, such a study should be considered SR. 
  2. The study of an extended wear contact lens is SR because wearing the lens continuously overnight while sleeping presents a potential for injuries not normally seen with daily wear lenses, which are NSR. 


Documenting the Determination 

By the virtue of the present guidance, the authority also describes how an institutional review board should document its SR or NSR determination. As it was mentioned before, all such determinations should be duly documented. In particular, the decision should be reflected in the respective meeting minutes containing a proper justification for the determination made, as well as additional documentation the determination is based on (e.g., a copy of the approval granted by the FDA for an IDE application related to the device in question). In case of an NSR determination, the documentation may include FDA’s NSR determination where the agency has made the determination (FDA will issue an NSR letter upon written request). 


Exempt Studies 

The scope of the guidance also covers the aspects related to medical device studies that are exempt from the requirements of the IDE regulations. As explained by the FDA, in such a case, the institutional review board should not determine the regulatory status of a study (SR or NSR). At the same time, it would still have to assess the study as set forth by the applicable regulations before it will be commenced. 

In this respect, the authority also describes several important concepts used in the context of such determinations, namely:

  • Minimal risk – a term used in the IRB regulations in part to identify certain studies that IRBs may approve through an expedited review procedure. 
  • Approval decision, which is different from SR/NSR determination. According to the guidance, the judgment about 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. 

In summary, the present FDA guidance describes the approach institutional review boards should apply when assessing clinical studies and making determinations on the significance of risks associated thereto. The document also outlines the responsibilities of IRBs and clarifies certain important aspects related to the determination of the regulatory status of a medical device study. 



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