On June 14, 2013, FDA issued a draft guidance, “FDA Decisions for Investigational Device Exemption (IDE) Clinical Investigations,” to provide clarity around certain IDE decisions, and to introduce a “voluntary program intended to facilitate the development of trial designs that may support a marketing approval or clearance.” Draft Guidance, at 2.
After evaluating an IDE, FDA takes one of the following three actions: approval, approval with conditions (traditionally referred to as “conditional approval”), or disapproval. The draft guidance focuses primarily on the second of these options, approval with conditions.
When FDA approves an IDE with conditions, the sponsor may begin enrollment in the clinical study but must respond to the issues identified by FDA within 45 days from the date of FDA’s decision letter. FDA may issue an approval with conditions “if FDA has determined that, despite some outstanding issues, the information provided is sufficient to justify human clinical evaluation of the device and the proposed study design is acceptable with regard to protection of study subjects.” Draft Guidance, at 4.
FDA may also grant a “staged approval,” which allows enrollment of a limited number of subjects while the sponsor responds to outstanding questions posed by FDA. Once the sponsor addresses those issues, it may expand enrollment in the clinical trial.
Though FDA may deny an IDE for a variety of reasons, section 601 of FDASIA, which modified section 520(g) of the FDC Act, specified that FDA may not disapprove an FDA based on a finding by FDA that the investigation may not support a marketing application. In the draft guidance, FDA notes that, while it will abide by this requirement not to disapprove an IDE that may not support a marketing application, it believes that the sponsor will benefit from knowing what modifications FDA believes are necessary to obtain approval. FDA states that it “will convey such considerations to the sponsor to provide greater clarity and predictability. In addition, FDA will convey certain considerations that FDA believes will be important for future submissions related to the proposed investigation.” Draft Guidance, at 9.
FDA will communicate these considerations in any combination of the following: study design assessment (e.g., are endpoints appropriate), study design considerations (e.g., randomization, statistical plan, enrollment criteria, blinding), or future considerations (e.g., limitations of the data with regard to supporting certain claims or indications, or required non-clinical testing).
Pre-Decisional IDE Review Process
This process is intended to “provide sponsors with information regarding study designs that will support market approval or clearance.” Draft Guidance, at 12. This process, known as a “Pre-Decisional IDE,” is “a voluntary approach to enable sponsors to obtain timely feedback from review staff on a near-final IDE application, with the opportunity for a mid-cycle interaction with the review team to promote a clearer understanding and quicker resolution of major issues with device or subject safety as well as study design.” Id. FDA is implementing this program in the hopes it will result in faster approval of IDEs that may support a marketing application. Eligibility is limited to pivotal studies for which an IDE is required.
The initial step of the application process is similar to that of a traditional IDE. Within five days of submission, FDA will evaluate whether the application is eligible and sufficiently complete for substantive review. One the application is accepted, a 30-day review clock begins.
At the end of the review cycle, FDA will issue to the sponsor questions agreed to by division management that would, if the application were submitted as an IDE, lead to a disapproval, result in an approval with conditions, or constitute a design consideration that FDA believes would not support a marketing application. Draft Guidance, at 14.
A meeting to discuss the application will be scheduled to occur within 15 days after the end of the 30-day period, or at another time agreed to by both FDA and the sponsor. The meeting should be no more than 90 minutes, and the sponsor must provide meeting minutes to FDA within seven days of the meeting.
After the meeting, the sponsor may choose to request the Pre-Decisional IDE be converted to an actual IDE. Such a request must be made within seven days of the meeting, and FDA will issue the decision letter within 15 days of receipt of the request. The inclusion of any additional information in the conversion request will result in the commencement of a standard IDE review, with a decision to be rendered within 30 days.
If the sponsor does not request a conversion, FDA must provide written feedback within 15 days of the meeting, including any deficiencies or recommendations noted during the review. The sponsor may then submit a formal IDE application; respond to the issues identified by FDA in the original Pre-Decisional IDE; or respond to FDA’s feedback and submit a request to repeat the Pre-Decisional IDE process.
It is not immediately obvious from the draft guidance precisely how a sponsor will benefit from the multi-step Pre-Decisional IDE process. If there are no concerns with the IDE, the review time is the same—30 days. If there are concerns, the sponsor and FDA will engage in a series of exchanges to resolve the issues. It may offer more opportunity for interactive feedback from FDA, but it is not yet clear if it will actually lead to faster IDE approvals or a higher percentage of IDE approvals. Nevertheless, for complicated submissions, it may provide more in-depth, useful feedback at an earlier stage in the review process, giving the sponsor an opportunity to better understand and address FDA’s concerns.