The US Food and Drug Administration (FDA) has finally issued its final rule establishing requirements for the de novo classification process. The de novo process allows FDA to establish new product classifications for low- to moderate-risk medical devices that meet existing device classifications, thereby significantly easing the regulatory authorization pathway. Without establishment of the new product classification, the device would by default be deemed a Class III device and thus require submission of a pre-market approval (PMA) application.

The de novo pathway has become popular over the last several years as new medical device technologies and intended uses are developed that do not align with existing device classifications. Of particular importance, the de novo pathway has been used by FDA to authorize digital health products—i.e., Software as a Medical Device (SaMD)—and devices that incorporate artificial intelligence technologies.

In the final rule, which will take effect on January 3, 2022, FDA explained that the requirements’ purpose is two-fold: (1) ensure devices are classified appropriately to protect the public health; and (2) limit unnecessary FDA and industry expenditure incurred when devices for which general and special controls provide a reasonable assurance of safety and effectiveness are subject to premarket approval.

MAIN PROCEDURES AND CRITERIA UNDER FINAL RULE

• Applicability: The final rule codifies the two pathways for seeking use of the de novo process: (1) the manufacturer receives a not substantially equivalent (NSE) determination from FDA after submission of a 510(k) because FDA concludes there is no predicate upon which to establish substantial equivalence; or (2) the manufacturer determines there is no predicate for their device and directly proceeds to the de novo process.
• Content: The final rule codifies the content of a de novo request. Specifically, the request must include administrative information, regulatory history, device description, indications of use, classification summary information, clinical and non-clinical study summaries, benefits and risks of device use, and performance data demonstrating safety and effectiveness.
• Efforts to Obtain Information: The final rule clarifies that applicants must conduct “reasonable efforts” when compiling information for a de novo request. This is particularly important when determining whether an existing classification or legally marketed predicate exists. If either does exist, the applicant’s device is not likely eligible for the de novo pathway.
• Review Timelines: The final rule codifies that within 15 days of receipt of a request, FDA will determine whether the request has been administratively accepted (i.e., the request is not incomplete or ineligible for the de novo pathway). If accepted, the final rule codifies that FDA will make a decision on the request within 120 days of the submission being accepted for substantive FDA review (the review clock pauses when additional information is requested from the applicant).
• Combination products: The final rule confirms that the de novo process can be used to seek authorization of combination products (e.g., drug/device products). The final rule explains that FDA will consider safety and effectiveness questions relating to the combination product as a whole, each constituent part, interactions between them, and user/patient interaction with the product.
• Pre-decision inspections: Despite industry push back in response to the draft rule, the final rule notes that FDA may conduct a pre-decision inspection, and the results of the inspection can be a basis for denying a de novo request (pre-decision inspections are not generally conducted in the 510(k) program but are required in the PMA program). In the comments to the final rule, FDA explains that pre-decision inspections would likely concern a small percentage of de novo requests. For example, FDA may conduct an inspection in cases where it needs to verify the integrity of the data, or if there are misconduct complaints at one or more clinical investigational sites and the results from the clinical investigation are used to support the request. FDA may also conduct pre-decision inspections if FDA has quality concerns or when there are critical or novel manufacturing processes that may affect device safety and effectiveness.

EFFECTS ON DE NOVO PATHWAY

The final rule generally codifies FDA’s expectations concerning the de novo pathway. With codification of the final rule, plus the continued development of medical devices that should not be subject to the onerous PMA process, the number of de novo requests will likely increase. In light of COVID-19 and its continued impact on FDA resources, there is a possibility that de novo requests will take more time to review despite issuance of the final rule.

Moreover, although FDA indicates that pre-decision inspections should only impact a small number of de novo applicants, manufacturers should be ready in case an inspection request is made. This is particularly important for startup companies whose quality system may not be fully mature at the time the de novo application is made.

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