The Food and Drug Administration (FDA) has published an information sheet guidance describing the regulatory aspects related to the Significant Risk and Nonsignificant Risk medical device studies. The document is intended to provide additional clarifications and recommendations to be considered by the parties, interested in placing their medical devices on the US market (sponsors), clinical investigators, and also the representatives of the regulating authorities engaged in the process. 

Due to its legal nature, the guidance does neither introduce any rules nor impose any obligations for the parties involved. The Agency explicitly states that the alternative approach could be applied, providing that such an approach complies with the applicable regulatory requirements and has been agreed with the Agency in advance. It is also important to mention that the information sheet guidance document has been initially issued in January 2006, and has not been subject to any additional reviews or amendments, except the revision conducted to update the examples contained therein and clarify the responsibilities of the regulating authorities, as well as to align it with other FDA regulations. 

Regulatory Background 

As it was already mentioned before, the present FDA guidance contains additional clarifications to be considered by the medical device manufacturers, their authorized representatives, clinical investigators, and also institutional review boards (IRBs) when conducting a risk-based determination of clinical studies. In particular, the document describes the regulatory aspects related to significant risk and nonsignificant risk medical device studies. 

In accordance with the Investigational Device Exemptions (IDE) regulation (21CFR 812), all medical device studies coulee divided into three types:

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

The present document addresses the first two types, while the details about the third one are provided in a separate guidance document issued by the FDA. 

Study Type Determination 

The Agency describes the criteria to be applied when determining the risk type of a medical device study subject to review. According to the document, in case of significant risk studies, the following criteria are applicable: 

  • It 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 present 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. 

The FDA states that all medical device studies that do not meet the criteria listed here should be classified as nonsignificant risk studies.

Under the general rule, a party interested in placing a medical device on the market (a sponsor) conducts the initial risk determination and communicates the decision taken to the institutional review board. At the same time, the parties engaged may also ask the Agency to assist in risk determination. In case there is no final determination made by the FDA, the institutional review board should determine the risk type of each medical device clinical study. In case of any discrepancies, the determination made by the FDA should prevail and thus be deemed final. 

Medical Device Study Types in Detail 

According to the present FDA guidance, the main differences between significant risk studies and nonsignificant risk studies are in the following aspects:

  • The IDE approval process,
  • The sponsor’s record-keeping and reporting requirements. 

Further, the FDA guidance states that in case of significant risk medical device studies, a sponsor shall comply with the regulatory requirements set forth under the IDE regulations at 21 CFR 812 and also to have the IDE application approved by the regulating authority in advance. According to the document, the nonsignificant risk medical device studies should comply with the abbreviated requirements set forth by 21 CFR 812.2(b) in terms of labeling, IRB approval, informed consent, monitoring, records, report, and the prohibition against promotions. At the same time, a sponsor of the NSR medical device study is not obliged to make reports to the regulating authority. The requirement to have an IDE application approved by the Agency could be also waived. Moreover, in the case of a nonsignificant risk medical device study, there is no obligation to inform the FDA about the IRB approval. In other words, an NSR medical device study could be commenced once approved by the IRB without the need to inform the Agency since the approval of the latter is not required.

Responsibilities of the Parties

In order to assist all the parties involved in complying with the applicable regulations, the present FDA guidance also outlines the scope of responsibilities of each party. 

For instance, depending on the type of the medical device study, the responsibilities of the study sponsor would include: 

  1. In case of nonsignificant risk medical device studies, a sponsor shall (a) provide the IRB conducting the review with the information necessary to assess the risks associated with the study and justify the determination made by the sponsor, including the description of the medical device in questions, suggested investigation plan and other details; and (b) notify the IRB about the NSR determination of a study made by the FDA – if the one is present – to simplify and facilitate the review process. 
  2. In case of significant risk medical device studies, a sponsor shall (a) submit an IDE application to the regulating authority in order to obtain its prior approval; (b) inform the clinical investigators about the significant risk status of a medical device study and ensure compliance with the applicable regulatory requirements; (c) provide the IRB with the appropriate IDE number and approval letter upon request. The Agency also mentions that a significant risk medical device study sponsor is also allowed to apply for an IRB review prior to the approval of the IDE application by the FDA. At the same time, the study subject to review should be commenced only after the IDE application would be approved by the FDA. 

The document also describes the corresponding responsibilities of the IRB. According to the document, an institutional review board shall: 

  • Have the standard operating procedures describing the approach to making significant risk and nonsignificant risk determinations. According to the document, making such determinations constitutes one of the IRB`s responsibilities in the course of the initial medical device study review. 
  • Make the appropriate determination based on the information about the medical device study subject to review to be submitted by a study sponsor. Such information includes, inter alia, the description of the medical device in question, the suggested investigation plan, and other details the IRB may reasonably need to review the application. 
  • Approve the study if it meets the criteria for nonsignificant risk medical device study. 
  • Inform the study sponsor about the SR determination made.

Summarizing the information provided here above, the present FDA guidance describes the way the type of the medical device study should be determined depending on the risks associated thereto. The document also outlines the responsibilities of all the parties involved and describes the appropriate procedures.

How Can RegDesk Help?

RegDesk is a next-generation web-based software for medical device and IVD companies. Our cutting-edge platform uses machine learning to provide regulatory intelligence, application preparation, submission, and approvals management globally. Our clients also have access to our network of over 4000 compliance experts worldwide to obtain verification on critical questions. Applications that normally take 6 months to prepare can now be prepared within 6 days using RegDesk Dash(TM). Global expansion has never been this simple.