September a Guidance Drop Month for FDA

September was an unusually busy month for the FDA’s device center, which released more than 20 draft and final guidances in the final 30 days of fiscal 2019. Several of these documents are related to the de novo device program, but the agency also updated its approach to the humanitarian device program as required by recent legislation.

Humanitarian Use Guidance Updated
The final guidance for the FDA’s humanitarian device exemption (HDE) program explains how the agency determines whether the sponsor has demonstrated a probable benefit, although the final encodes the new limit for humanitarian use devices of 8,000 per year as seen in the 21st Century Cures Act. Another change due to statutory mandates, in this case the Food and Drug Administration Reauthorization Act of 2017, is that the sponsor need not rely on a local institutional board, a change intended to offer some efficiencies in the conduct of multi-site clinical investigations.

The HDE guidance is applicable to devices reviewed by both the Center for Devices and Radiological Health and the Center for Biologics Evaluation and Research. HDE applications will be reviewed within 75 days under this policy, a much quicker turn-around than is available to PMA devices at 180 days. Device makers are now allowed to make a profit on these devices unless the volume sold exceeds the annual distribution number limit of 8,000, and manufacturers are required to file an annual report on profitability only if the price charged for the device exceeds $250.

De Novo Program Rates Three Guidances
The agency also released three guidances pertaining to the de novo premarket program, including the final guidance spelling out the actions both device makers and the agency can take in relation to these applications. Also topical for the agency’s purposes is how those actions might affect review goals under the current user fee program.

The FDA said the clock will stop on a de novo application should the agency have questions that cannot be answered in a reasonable amount of time, although the guidance does not provide any metrics for “reasonable.” The hold goes into effect when the FDA issues the request, and the guidance states that a request for additional information stops the review clock and “marks the end of an FDA review cycle.” The clock will resume once the agency is in receipt of a complete response from the sponsor.

De novo submissions are now subject to user fees, and the target turn-around time for de novo petitions is 150 days, although the percentage of applications that must meet that deadline varies by year. For fiscal 2018, the target ratio of applications that met the 150-day target was 50%, but that goes up to 70% in the final fiscal year of this user fee schedule, which is FY 2022. The review staff assigned to that application will be available to discuss any problems with the sponsor if it is still outstanding at 180 days, at which point the reviewers will discuss next steps, including the deadlines for completion of those next steps.

The final guidance for acceptance review of de novo applications employs the same refuse-to-accept (RTA) principles that govern RTA policies for 510(k) and PMA applications. One important difference for the de novo version is that the sponsor has to document that there is no cleared predicate on the market, assuming the device in question is not a class III device. The FDA staff is tasked with determining whether any 510(k) or PMA applications are in process for devices with the same technology and same indication for use.

There are a number of considerations for de novo applications that are combination products, including whether the drug component for a drug-device combination product is the subject of a patent. The guidance includes a checklist which the sponsor is advised to complete prior to filing the application with the FDA. The checklist starts with four questions regarding whether the device in question is a combination product, highlighting the agency’s interest in resolution of any combination product questions before the de novo reaches the FDA.