CDRH Reviews Early Feasibility Study Advantages
CDRH says early feasibility studies conducted in the U.S. can give medical device developers important FDA feedback early in the development process, which may improve the development strategy and reduce the chances that unnecessary testing is completed. Speaking on a device clinical trial webinar (view recording/view transcript) earlier this month, CDRH policy analyst Carla Wiese said these studies can also “increase the predictability of data requirements for a future study or commercialization needs.”
An early feasibility study IDE is reviewed like any other IDE, according to Wiese. It is used when there are “significant unknowns” about how the device will perform because the device is early in development or because it has a new intended use. Typically, a small number of subjects are enrolled in these clinical investigations in order to develop an initial safety and effectiveness evaluation or to establish a proof of concept, she said.
Wiese directed webinar attendees to a final guidance on “Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human Studies” for more detailed information. She noted that one key element is that the guidance allows for timely device and clinical protocol changes. “More changes can now be made during the study through a five day notification rather than FDA approval and there's a contingent approval option,” she said. “This is the approval of anticipated or proposed device changes that can be obtained contingent on the completion of an agreed upon test plan and acceptance criteria. And lastly, the guidance contains recommendations on pre-submission content including an example risk assessment method is provided.”
Another key element in the guidance is the concept of doing the right testing at the right time, Wiese said. “I believe there has been some confusion about how and why less non-clinical testing may be needed to support an early feasibility study,” she said. “FDA recognizes the value of alternative non-clinical test methods in leveraging data. For example, different test methods may be more relevant for small batches. An example of this is the single lot ethylene oxide sterilization versus completing a full ethylene oxide sterility validation. Also, some test data could be leveraged. For example, some biocompatibility and points could be leveraged from an animal study if one is conducted. And some test data could be leveraged from a previous version of the device.”
Wiese recommended that submissions for early feasibility studies be well planned. An pre-submission meeting may be useful for novel ideas. “An initial pre-submission should include all the information described in the guidance with the goal to agree upon the risks in the test plan,” she said. “Additional pre-submissions should be submitted as needed, for example, if test requirements are uncertain or to discuss the clinical protocol... The use of pre-submissions to discuss the test plan and the clinical protocol can be very useful in the following ways. It can be useful when the non-clinical testing needed is unclear and be used to agree upon the test plan that will support an IDE submission with FDA, and you avoid the need to redo expensive and time consuming testing. And it may help determine appropriate clinical mitigations and reporting requirements in the patient population for whom the benefit risk profile supports inclusion into their early feasibility study.”
Another recommendation is that sponsors should be able to describe why additional non-clinical testing will not be informative and that a human clinical study is appropriate, Wiese said. Submissions should provide clear identification of potential risks and how they will be addressed (e.g., non-clinical testing, clinical mitigations or reporting), she said. An explanation should be provided for why the plan is sufficient, “and it's helpful to explain what can and cannot be learned from the bench test and animal models and why any information to be leveraged is directly applicable to this study,” she added. “And lastly, it may be helpful to list which tests will be done to support the early feasibility study versus which will be done to support a later study, if applicable.”