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The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of medical devices, has published a guidance document dedicated to the Investigational Device Exemptions (IDEs) for early feasibility medical device clinical studies, including certain First in Human (FIH) studies. The document is intended to assist medical device manufacturers and other parties involved in operations with medical devices in interpreting the applicable provisions of existing legislation and following the requirements set forth therein. At the same time, the guidance itself is not intended to introduce new rules or requirements, so the provisions thereof are non-binding in their legal nature. 

Regulatory Background 

The authority acknowledges the importance of introducing a favorable regulatory framework that will encourage medical device manufacturers to develop new products utilizing novel technologies to provide healthcare professionals and patients with more flexibility when choosing diagnosing and treatment options, especially in cases when alternative solutions are either unavailable or associated with significant risks for patients’ or public health. The present document addresses the regulatory matters associated with the early clinical evaluation of new products based on proper risk mitigation strategies intended to ensure the safety of study participants. In this respect, the authority states that an early feasibility study IDE application must comply with section 520(g) of the FD&C Act [21 U.S.C. §360j(g)] and 21 CFR part 812; however, the procedures and conditions prescribed for IDEs may vary depending on the type of clinical study. 

The present document is intended to provide additional clarifications regarding the existing regulatory framework related to submitting early feasibility study IDEs and review of such applications by the authority. As further explained by the FDA, the respective policy addresses the following matters: 

1. Due to the specific nature of an IDE framework that is intended to ensure the availability of novel medical devices and reduce regulatory burden, the nonclinical data the authority will expect to receive will be less than in the case of traditional pathways. The Agency follows such an approach since early feasibility studies are usually undertaken in situations when additional information that is reasonably necessary to assess the safety and effectiveness of a medical device in question could be obtained only in the course of a clinical study. According to the guidance, identification of the data necessary to support an early feasibility study should be based on a thorough device evaluation strategy that describes the device procedure, performance, and basic safety-related attributes and addresses the potential failure modes. The authority also mentions that the purpose of the approach described herein is to accelerate the commencement of clinical studies and reduce the regulatory burden associated thereto. 
2. Moreover, the present policy describes the approach to be applied concerning changes to the study protocols. In particular, the guidance describes a new policy to be applied provided that the general requirements are followed, namely:
   1. More types of modifications that can be made under a 5-day notification without prior FDA approval, as compared with other types of studies;
   2. A contingent approval process that permits changes contingent upon acceptable nonclinical test results without requiring additional FDA action; and 
   3. Interactive review of IDE supplements and amendments. 

The document also outlines the main principles associated with the IDEs related to the early feasibility studies about clinical protocols, protection measures, and strategies to be applied to mitigate the risks for study participants. 

Furthermore, the authority also mentions that parties initiating an early feasibility study (sponsors) are encouraged to contact the Agency before the commencement of a study to request additional information. In particular, the Pre-Submission pathway could be applied. In such a way, a sponsor may obtain informal feedback regarding the intended clinical trials and specific aspects thereof including such elements as a draft clinical study protocol. 

The authority additionally emphasizes that sponsors should not initiate clinical trials unless all nonclinical methods to collect additional information necessary to assess the safety and effectiveness of the device are not exhausted. 

The Agency also states that the present guidance is not exhaustive, hence, it does not cover any elements of an IDE application, nor prescribes the way the investigation itself should be performed. Moreover, the scope of the guidance covers only the general rules and requirements, while for the device-specific aspects, sponsors should check respective guidance documents, as in certain cases, specific information could be required due to the nature of the device subject to review, its characteristics, and features. Thus, the sponsors are encouraged to contact the Agency before commencing the study and clarify the requirements associated thereto. 

Targeting Approval for an Early Feasibility Study IDE Application 

As it was mentioned before, the scope of information required about an early feasibility study is different from the one required under the general pathway. Thus, it is important to ensure the IDE application explicitly indicates that it refers to an early feasibility study, while the use of this pathway should be duly justified. For this purpose, an interested party should address the following questions: 

1. What is the clinical condition to be treated or assessed by the device?
2. What are the standard of care for the clinical condition and expected clinical outcomes associated with the standard of care?
3. What are the anticipated benefits associated with the use of the study device?
4. Is the information included in the Report of Prior Investigations adequate to support the initiation of the study?
5. Does the Investigational Plan include thorough risk analysis, sufficient risk mitigation strategies, adequate human subject protection measures, and an appropriate clinical study protocol?
6. Are the potential risks associated with the device likely to be outweighed by the anticipated benefits of the early feasibility study, that is, is the initiation of the clinical study justified based on the clinical need for the device, Report of Prior Investigations and Investigational Plan? 

Based on the information provided by the sponsors, the authority may take one of the following decisions:

• Approve an investigation as proposed by the applicant;
• Approve an investigation with conditions to be imposed; or
• Disapprove an investigation in case it will be identified that the benefits do not outweigh the risks associated thereto. 

In summary, the present FDA guidance provides an overview of the regulatory framework for IDEs associated with early feasibility studies and clarifies important aspects associated thereto. The document also highlights the main principles to be followed by the sponsors when preparing and submitting an application for the authority’s review and approval. 

Sources:

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-device-exemptions-ides-early-feasibility-medical-device-clinical-studies-including

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