Medical device experts discussed how to avoid setbacks with submissions to the US Food and Drug Administration’s (FDA) breakthrough devices program and the Safer Technologies Program (STeP) and in responding to deficiency letters at the RAPS Global Regulatory Strategy Conference on 6 March.
Regulatory consultants Melissa Hall of Statera Regulatory Consulting and Caroline Rhim of Evera Regulatory Advisors, shared their perspectives on the current medical device premarket landscape, provided an update on approvals, and offered case studies explaining what submission strategies work – and what does not work. They also discussed effective communication strategies to get submissions approved. Both speakers were former FDA reviewers.
Trends in breakthrough, STeP programs
Rhim said that despite a slight blip over the past few years, the number breakthrough designations have grown steadily. There were 167 breakthrough designation requests granted in 2023, up slightly from 166 in 2022, and a large increase from the program’s early years and from its predecessor, the Expedited Access Pathway (EAP).
She added that the numbers for STeP are “not as impressive,” though the number of devices participating is “still climbing.” There have been 35 total devices approved for the STEP program, 15 of which were designated in 2023.
The STeP program, announced in 2020, is intended for devices and device-led combination products that are expected to improve patient safety and target conditions that are less serious than those covered by the breakthrough program. (RELATED: Safer technologies program finalized by FDA, Regulatory Focus 5 January 2021)
Avoiding derailment
Rhim also offered a case study showing why an application for a novel software device was rejected for breakthrough designation. The sponsor chose the wrong type of meeting to have with FDA on the device. The sponsor had requested sprint discussions with FDA instead of requesting more intensive meetings that would have allowed for more questions.
Sponsors can choose to interact with the FDA to obtain feedback on their device development through either sprint discussions, requesting a discussion on a data development plan, or requesting agreement on a clinical protocol.
FDA’s final guidance on the breakthrough device program says that sprint discussions are meant “to support sponsors needing timely resolution of potentially novel issues.” FDA offers sprint discussions with the goal of reaching mutual agreement on a specific topic within a set period, such as 45 days.
Rhim said the sprint discussions are designed for sponsors to ask FDA focused questions on particular program areas. But in this case, the sponsors used these meetings to ask broad questions that were not particularly focused. FDA by default resorted to giving them a “ton of feedback, which kept snowballing” with each meeting.
She added that the sponsor was asking FDA questions that “they should have answered themselves.” The sponsor had ten or more such sprint discussions with FDA.
Rhim said that “this regulatory pathway started to spiral out of control with every meeting there was more feedback to address.”
In another example, a novel class III implantable device was granted breakthrough device designation. In this case, Rhim explained that there was one “focused and to the point,” sprint discussion on the clinical protocol.
Rhim also offered other suggestions to avoid derailments, such as the use of tables in submissions. She said that “tables are wonderful, nothing made me more excited that tables were that were already digested for me.”
In addition, she advised sponsors to use summary “trackers” and called them a helpful tool to capture the regulatory history of the device and how the sponsor addressed agency feedback. Also, sponsors should use a traceability tool that shows how the submission was updated from a previous version.
Responding to deficiency letters
Another important point Rhim stressed is that sponsors should respond holistically to deficiency letters, and not have different parts of the company only look at the deficiencies related to their disciplines.
Instead of asking each discipline within the company respond to the deficiency in their area, such the biocompatibility, the clinical and the statistical staff who just “read their part and skim over everything else.” She said that “there are common threads that run through all deficiency letters. We recommend that every team letter read the entire deficiency letter. You will start to pick up on some common themes.”
Remote hires and review cross collaboration
On a different note, Hall addressed some recent FDA hiring patterns, observing that over the past couple years FDA has allowed more workers to work remotely. The agency is also hiring more staff outside of the Washington, DC metro area.
On the review front, Hall noted that FDA is allowing staff to review applications that may be outside of their areas of expertise. This cross-collaboration is being done under the Minors program, which was created under the Total Product Lifecycle (TPLC) reorganization in 2020, which allows employees to work outside of their disciplines to broaden their knowledge base.
“The Minors Program allows staff to cross collaborate in different areas, you may see some people that typically work in OSEL [Office of Science and Engineering Laboratories] that want to experience what it is like to be a lead reviewer, or you have a lead reviewer who wants to get into the policy space and understand how the de novo program works.”
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