The new article describes in detail the responsibilities of the regulating authority concerning the determination of risk associated with medical device studies; and also provides some examples illustrating the way the approach described in the guidance should be applied. Apart from that, the article provides a summary of the main considerations related to risk determinations for medical device clinical studies. 

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 nonsignificant risk (NSR) medical device studies. The said classification is used to determine the level of regulatory scrutiny the study should be subject to depending on the risks associated thereto. The document provides additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered to ensure compliance thereto. At the same time, provisions of the guidance are non-binding, nor are intended to introduce new rules or impose new requirements. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the respective legislation and has been agreed with the authority in advance.


FDA’s Responsibilities 

As was mentioned in the previous articles dedicated to the matter, the determination made by FDA should be final and non-negotiable. At the same time, the authority would assess only the studies that are notified by their sponsors, or concerning which an institutional review board (IRB) or a sponsor requested additional advice. Furthermore, should the authority disagree with the NSR determination made by an IRB, the study in question should not be commenced unless the corresponding Investigational Device Exemption (IDE) application will be approved by the FDA. 

In case a sponsor deems a study to be of significant risk and submits an application to FDA, while the latter determines the study to be a nonsignificant risk, a sponsor will be notified accordingly. After this, such a study should be subject to review by the institutional review board according to the general procedure for nonsignificant risk studies. 


To assist study sponsors and other parties involved in determining the regulatory status of clinical studies, the guidance also provides some examples illustrating the way the approach described in the document should be applied. The said examples are describing the most common situations. At the same time, FDA additionally emphasizes that the mere inclusion of a medical device in the nonsignificant risk list should not be construed as a final determination, as the proposed use of a medical device in question should be taken into consideration as well. 

According to the guidance, the examples of nonsignificant risk devices include:

  • Caries removal solution;
  • Contact lens solutions intended for use directly in the eye using active ingredients or a preservation system with a history of prior ophthalmic/contact lens use or generally recognized as safe for ophthalmic use;
  • Conventional gastroenterology and urology endoscopes and/or accessories;
  • Conventional general hospital catheters;
  • Conventional implantable vascular access devices (ports);
  • Conventional laparoscopes, culdoscopy, and hysteroscopes;
  • Daily wear contact lenses and associated lens care products not intended for use directly in the eye (e.g., cleaners, disinfecting, rinsing, and storage solutions). 

As further described by FDA, significant risk devices include, inter alia, the following ones: 

  • Surgical lasers for use in various medical specialties;
  • Tissue adhesives for use in neurosurgery, gastroenterology, ophthalmology, general and plastic surgery, and cardiology;
  • Breathing gas mixers;
  • Bronchial tubes;
  • Aortic and mitral valvuloplasty catheters;
  • Cardiac mapping and ablation catheters;
  • Coronary artery retroperfusion systems. 



According to the guidance, the significant risk / nonsignificant risk determination is vitally important in terms of a pathway to be followed when developing and conducting a medical device clinical trial. 

Under the general rule, the initial risk-based determination should be performed by the party responsible for a clinical trial (a sponsor) and applying for the respective approval. Should a sponsor decide that the study in question is a nonsignificant risk, a request for approval should be submitted to an institutional review board which will conduct its assessment to verify the correctness of the determination made by a sponsor. In case a nonsignificant risk determination is confirmed, the study could be commenced without additional approval from the regulating authority. However, should it be determined that the study in question should be classified as a significant risk, the corresponding Investigational Device Exemption application should be approved by FDA first, and the study should not be commenced before such approval is granted. 

The factors to be taken into consideration when making the said determination should include, inter alia, the following ones:

  • The proposed use of a medical device is subject to investigation;
  • The nature of harm potentially resulting from the use of the device;
  • The need for additional procedures (e.g., surgery) for a study subject, since this would impact the risks associated with the study. 

In summary, the present FDA guidance describes the approach to be applied by study sponsors, institutional review boards, and the authority’s staff when determining the regulatory status of a clinical study. The document highlights the key factors to be taken into consideration when making such a determination and also provides additional clarifications concerning the regulatory procedures associated thereto. 



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