FDA’s De Novo Program Gains Momentum

Regulatory NewsRegulatory News | 04 April 2019 |  By 

The US Food and Drug Administration (FDA) has been steadily increasing the annual number of granted de novo classification requests in recent years and hit a record of 44 de novos granted during 2018.

The de novo premarket review pathway, used for novel, low-to-moderate-risk devices that are not substantially equivalent to already marketed devices, has increasingly attracted interest in the medical device ecosystem, particularly after the quick turnaround for Apple’s granted de novo classification requests last September.

The pathway is expected to see more use now and in the coming years partly due to a December 2018 proposed rule, which seeks to provide structure, clarity and transparency on the classification process. Further, a 2014 proposed rule in the de novo space was finalized last December to clarify certain processes.

A set of four final and one draft 2017 de novo guidances will also spur the development of the program, at FDA’s Center for Devices and Radiological Health (CDRH) de novo program lead Sergio de del Castillo said at RAPS’ 2018 Regulatory Convergence. Although some have questioned a part of the de novo proposed rule that would allow FDA to conduct manufacturing site inspections as part of the review process for de novo classification requests.

Castillo noted that 2017 had been a “banner year” for the program under the first performance goals on review timelines added by the fourth reauthorization of the Medical Device User Fee Amendments (MDUFA IV). The average time to de novo MDUFA decisions was reduced compared to the early 2000s.

With the release of the 2018 proposed rule, the agency cited “marketing authorizations for 235 safe and effective novel medical devices” made possible through the de novo pathway. FDA added that 170 of the 235 marketing authorizations “occurred after 2012.” These numbers are now up to 250 and 185 as of Thursday. Focus’ analysis of the public de novo database revealed an uptick that began around 2011.

The graphic below illustrates how the de novo program turned over a new leaf in 2011, coinciding with the release of CDRH’s February 2011 white paper on medical device innovation. Streamlining the de novo pathway was a goal CDRH set for this white paper, with the deliverable having been the subsequently issued de novo draft guidance on the evaluation of automatic class III designation.

The graphic below also suggests the de novo guidances provided needed clarifications for greater use of the pathway, starting with the white paper’s 2014 draft guidance up to when this was finalized in October 2017 in conjunction with the issuance of the draft guidance on the acceptance review policy.

It further depicts 2018 as the new “banner year” and notable headway in the first few months of 2019 compared to previous years, despite the troubles FDA faced over the longest government shutdown in US history.
Number of Granted De Novos

A potential catalyst to the de novo program relates to the agency’s test plan from January to operationalize the envisioned organization-based total product lifecycle concept of CDRH’s Digital Health Software Pre-Certification (PreCert) pilot program. PreCert is to be tested upon the request of one of the nine FDA-selected companies using a two-fold approach to reviews with a de novo and an FDA excellence appraisal model. CDRH decided the de novo pathway was the best fit to test PreCert.

At least some of the nine PreCert participants, selected in 2017, are already experienced users of the de novo pathway. Roche tops the list with the largest number of granted de novos at four in total, followed by Apple with the two that were granted for atrial fibrillation applications. Pearl Therapeutics has one.

23andMe, though not a PreCert participant, is notably among those receiving four granted de novos, all for digital health products.

Focus’ analysis found the medical technologies that have gone through the de novo pathway since 2015 as of Thursday mostly target six areas of medical specialties, as the chart below suggests.
Regulation Medical Specialties

The push for greater use of and creating efficiencies around the de novo program is centered on facilitating the appropriate classification of new types of medical devices. Established in 1997, the de novo program serves an important role in reducing regulatory burden as the classifications it produces enable subsequent devices to use 510(k)s rather than the more burdensome premarket approval application pathway. Without de novo classifications, new low- to moderate-risk device types would be limited to PMAs.

Another reason the focus has shifted to more de novos relates to CDRH’s goal—set in January 2018—to have 50% of manufacturers’ novel devices come to the US first or in parallel with other major markets.

The agency’s recent proposal to limit manufacturers’ use of predicate devices 10 years or older led to some confusion regarding the expected result of greater de novo use. But both the push for more de novos and less predicates for 510(k)s are part of the same vision—modernization of the 510(k) pathway.

A continued uptick in granted de novos could in turn create a higher volume of 510(k)s. The agency has already indicated more actions on the 510(k) pathway’s modernization will continue throughout 2019.


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