The new article provides additional details regarding specific aspects related to the report of prior investigations.
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 certain First in Human (FIH) studies. The document is intended to provide medical device manufacturers with additional clarifications regarding the way the applicable regulatory requirements should be interpreted and followed, and also with the recommendations to be taken into consideration when submitting the respective applications. At the same time, the authority additionally emphasizes the non-binding legal nature of the guidance and states that an alternative approach could be applied, provided it complies with the applicable legislation and has been agreed with the FDA in advance. The aspects covered by the scope of the guidance include, inter alia, the ones related to different types of testing, such as bench or laboratory testing, or in vivo animal studies.
Bench and Laboratory Testing and Computational Modeling
As was mentioned in previous articles dedicated to the topic, the idea of the IDE as a simplified pathway itself does not require the whole set of testing to be conducted before the product will be approved by the authority, as the IDE framework is intended to facilitate placing novel medical devices on the market to ensure access to innovative products and reduce the time needed for them to be made available for healthcare professionals and patients. It was explained in the previous article that the approach to be followed by a study sponsor when determining the scope of information to be provided and the level of detail for such information should make its decision utilizing a risk-based approach. In particular, the aspects to be considered should include the functionality of the device, potential issues that may occur, and also the impact such issues may have on the overall functionality of the device, resulting in patients being exposed to additional risks. All these aspects should be duly reflected in the device evaluation strategy based on the information currently available to a responsible party.
Another method describes in the guidance is computational modeling (CM) which could be used for such purposes as:
- For long-term implants in which the boundary and loading conditions are known, CM may be used to predict the long-term durability of the device;
- For long-term implants in which the boundary and loading conditions are not well-defined, CM may be useful for iterative design modifications, where simulations can be used to optimize the device design or enhance the design of prototypes;
- For certain test scenarios, which cannot be evaluated using other nonclinical methods or clinically, CM may be used. For example, to aid in assessing MRI safety, CM may be used to simulate certain worst-case MRI conditions that cannot be replicated in an animal model and cannot be tested ethically in humans.
As in other complex cases, the authority encourages the sponsors to discuss the key points before commencing the study, especially if the methods to be applied are relatively new and not the ones that are typically used in similar situations.
In Vivo Animal Studies
The document also describes in vivo animal studies that could be conducted to collect additional safety and performance data that cannot be collected in any other way – for instance, how the organism responds to the use of the product in question. A study of this type could be performed in case additional information is needed to justify the commencement of an early feasibility study, and this information cannot be collected in another way.
An animal study should be based on the validated models to ensure the reliability of the results – in such cases, they could be used to predict corresponding risks to human patients who will be exposed. However, in case there are no validated models to be used, it is allowed to conduct animal studies addressing specific safety- or performance-related matters that cannot be investigated by the device of nonclinical testing, and the scope of testing should be limited to such matters. The authority also mentions that all the testing methods used by the sponsor should be duly justified. Furthermore, the FDA additionally emphasizes that animal studies should not be viewed as an alternative. Adequate bench testing, and whenever possible, protocols should apply the principles of reducing, replacing, and refine. For instance, the sponsor should consider the assessment based on computer simulation instead of the use of live animals. It is also important to mention that the accuracy and reliability of the study results also depend on its size – it should be large enough to show consistency in results, which would be significant enough to make conclusions. The size of a study could be limited in case it is conducted to support the commencement of an early feasibility study, while for the assessment of the safety and performance of a final device more significant study will be needed.
The document also refers to the Good Laboratory Practices (GLP) to be applied in animal studies as prescribed by regulation 21 CFR part 58 to ensure the accuracy and reliability of the data to be collected in the course of a study, as it will later be used to support applications for new trials or applications. However, in certain cases, it is allowed to use the data deriving from the studies that are not fully compliant with the said principles, provided that all the deviations are duly identified and thus would not impact adversely the reliability of the overall results. As in the case with other aspects, the authority encourages study sponsors to discuss future studies in advance to agree on the most important aspects.
Prior Clinical Information
Apart from the above mentioned details, the authority also expects an interested party to provide information about any prior clinical studies on the product in question. In case there are no clinical data related to the specific device, a sponsor may provide other relevant clinical information including the one related to:
- Similar or related devices utilized for the proposed intended use; or
- The subject device or similar devices are used for different purposes.
The authority also mentions that such information could be based on clinical use that took place in other countries. Should such information be available, study sponsors should provide a summary accompanied by the respective documentation.
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