The article provides a detailed overview of the regulatory requirements related to the information an interested party (a sponsor) shall submit to justify a study and its scope.
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 the Investigational Device Exemptions (IDEs) for early feasibility medical device clinical studies, including First in Human (FIH) studies. The document is intended to provide medical device manufacturers and other parties involved with additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered to ensure compliance thereto. However, it is important to mention that the document is not intended to introduce new rules or obligations, and provisions thereof are non-binding in their legal nature. Moreover, an alternative approach could be applied, provided such an approach complies with the respective regulatory requirements and has been agreed with the authority in advance.
Reports of Prior Investigations: Key Points
The present guidance describes, inter alia, the regulatory requirements set forth under 21 CFR 812.27 concerning the Report of Prior Investigations in the context of early feasibility studies. In particular, the authority explains the way these requirements should be applied, and also outlines the main points to be covered by the Report of Prior Investigations, which should contain sufficient justification of a clinical investigation. As further explained by the FDA, the information to be included in such a report should:
- Support an expectation of acceptable clinical use (e.g., successful device placement using a benchtop model that simulates clinical conditions and/or a suitable animal model) and that the device will function as intended;
- Address basic device safety, including, but not limited to, sterility, biocompatibility, software verification, and validation, electromagnetic compatibility, chemical compatibility (e.g., with contaminant drugs); and
- Characterize catastrophic failure modes and identify risk mitigation approaches.
The authority also mentions that the information provided by the interested party may derive from tests conducted using non-standardized methodologies. When deciding on a scope of testing required, a party responsible for testing should take into consideration potential failures and risks associated thereto, as well as the effectiveness of nonclinical testing for assessing performance-related matters.
Content of the Report
The document further describes in detail the information to be included in the Report of Prior Investigations. According to the recommendations, provided in the guidance, all the information should be provided in a structured way and separated as follows:
- Background. In this section, an interested party shall highlight the most important specific features of the product in question, especially the ones related to its design or intended patient population. This information will be taken into consideration by the authority when determining the applicability of an early feasibility study. As further explained by the FDA, this section should address the matters related to the clinical context of the study, description of the design concept, and also an appropriate justification of the scope of information required.
- Executive Summary. According to the guidance, the Executive Summary section should provide a summary of the information provided and an explanation as to why this information is adequate to support study initiation. In particular, in this section, a study sponsor should provide the details about nonclinical testing conducted, including the description of all the tests and acceptance criteria.
- Detailed Reports. This section should include the reports for tests conducted and additional information available to support the initiation of the early feasibility study. For instance, the section should include reports for all the tests conducted, a summary for nonclinical information, together with a summary of clinical information.
The guidance further describes in detail the way specific matters should be addressed in a Report of Prior Investigations to ensure completeness of the information provided.
As it was mentioned before, the Background section should contain information about the design of a medical device subject to review. In particular, it should describe in detail such aspects as:
- The design itself, includes the principal mode of action, main functions of the device, and also the way the product achieves its intended purpose.
- The intended use of a medical device, including the indication of specific conditions when the device should be used, as well as the respective limitations.
- The intended use environment.
- The duration of use for the device.
The information outlined hereinabove could be used to determine the scope of testing needed to ensure that all the important safety- and performance-related aspects are duly covered.
Device Evaluation Strategy
The details about the device evaluation strategy should be provided by a study sponsor in the Executive Summary section. In particular, this section should contain information about the testing already conducted. In this section, a sponsor should explain the reason for including the respective information in the report to justify the applicability of the IDE framework. The authority also encourages the sponsors to discuss the related matters in advance before the commencement of testing. For this purpose, the Pre-Submission framework could be applied. The authority also mentions that this becomes especially important in cases when:
- The sponsor is providing less nonclinical data as compared to what would be expected for traditional feasibility or pivotal study;
- There is no FDA guidance or voluntary standard specific to the device and intended use proposed to be studied; and/or
- Certain nonclinical tests are more relevant than others in addressing basic safety and potentially catastrophic failures or supporting basic device functionality.
The authority additionally emphasizes the importance of identifying the most important information needed to justify the study to be conducted. The FDA mentions that when making such a determination, the factors related to risks and benefits should be considered as well.
According to the guidance, the appropriate justification of testing would be necessary even in a case such testing is conducted following the applicable voluntary standard – in such a case, a study sponsor should duly justify the applicability of a respective standard. As it was mentioned before, an interested party may request feedback from the authority about the particular device evaluation strategy to be applied.
In summary, the present FDA guidance highlights the most important aspects to be considered when determining the scope of a study and its applicability in general. The document also outlines the scope of information the authority expects to receive as justification for a study to be conducted.
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