CDRH officials say pre-submission meetings can improve odds for de novo requests

TORONTO—With only about half of de novo submissions granted authorization, officials from the US Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) said that sponsors should take advantage of its pre-submission process and obtain data from investigational device exemption (IDE) trials to improve their products' chances of getting to market.

The CDRH officials made these remarks at the 2024 Medtech Conference, where they answered questions about the center’s ongoing work. Allison Komiyama, a regulatory consultant at RQM+, raised concerns about the low success rate for de novo classification request. She noted that according to Peter Yang, program lead for CDRH’s de novo program, only about 50% to 60% of de novo requests make it through the process to receive a classification order.

“It’s a little harrowing when we get a denial letter,” said Komiyama. “It’s happened three times. We’ve appealed all three, and all three of them have been reopened, and with post-marketing controls and labeling changes, the devices have been granted.”

Komiyama noted that filing de novo appeals is very resource intensive, not just for the companies but for FDA, and asked the CDRH officials about how they are training staff to ensure they understand the spirit of the agency’s de novo guidance and ensure they understand the potential harms of delaying products getting to market.

Owen Faris, principal deputy director at CDRH’s Office of Product Evaluation and Quality (OPEQ), noted that while the agency’s focus is on the benefits and risks of the products that they authorize, its goal is not to have zero risk. He said such a threshold is impractical. Instead, he said reviewers should evaluate products based on who the intended patient is, what the condition is, what the product does, what the agency knows about the benefits and risks, and what an acceptable level of uncertainty is.

“There are risks of putting products on the market that can harm patients, there are also risks in waiting to get all the data and get the perfect answer and 100% assurance that we have a product that is safe and effective,” said Faris “We have to accept uncertainty in our decision-making, and we have to empower our staff throughout the organization to take some reasonable risks, ask thorough questions, get answers to those questions, but recognize that we have to make a decision with some level of uncertainty every day.”

Faris noted that that kind of thinking applies to all marketing applications that come to FDA and to other discussions that happen at the agency. However, he also said that innovative products submitted via the de novo pathway pose an additional challenge because they are often unlike other products that come before reviewers.

While he acknowledged that the authorization rate is lower than other premarket pathways, he noted that such products are often low-risk and have low potential benefits. In such situations, he said it can be difficult for reviewers to determine the appropriate balance between risk and benefit.

“The company telling their story of how you have been thinking about this product and the journey you have both been on can be really helpful,” said Faris. “Companies who come in with a pre-submission before their de novo do better. That is one of the clearer pieces of data we see is that those companies are more likely to be able to navigate the process.”

“That just points to having a mutual understanding of what the product does, who the patients are that it's intended for, what the benefits are and what the risks are, what the level of uncertainty is about those benefits and risk, and how the product has been validated,” he added.

Michelle Tarver, CDRH acting director, added that another major indicator of a de novo product's success is that it already has an IDE. She said it shows that the sponsor has considered the clinical data it needs and can set them up for success.

“They have planned and thought about do they need clinical data as opposed to making the assumption that they are automatically a 510(k),” said Tarver.

CDRH officials say pre-submission meetings can improve odds for de novo requests

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