Jianyuan (Yuan) Hua, FDA Regulatory and Compliance Associate in New York, contributed to the drafting of this post.
On Tuesday, December 14, 2021, the U.S. Food and Drug Administration (FDA) hosted a webinar discussing the final rule, Medical Device De Novo Classification Process, and associated guidance document updates. The final rule, which will take effect on January 3, 2022, codifies the medical device De Novo classification process by adding new regulations at 21 CFR Part 860, Subpart D. Dr. Peter Yang, De Novo Program Lead at the FDA Center for Devices and Radiological Health (CDRH), led the webinar. Dr. Yang described the new De Novo regulations, explained how the regulations may or may not change the current De Novo review process, and answered questions from various interested parties.
A De Novo request is a type of premarket submission, requesting the FDA to classify a novel device into class 1 or class 2 based on a determination of reasonable assurance of safety and effectiveness (RASE). If the De Novo request is granted, the FDA creates a new classification regulation and the De Novo device can serve as the first predicate device of its kind. Subsequent requests will be a 510(k). While the final rule largely reflects the current review process, the FDA highlighted a few areas that stakeholders might be interested in.
- Refuse-to-Accept (RTA) Checklist. The most significant change is the updated acceptance checklist. 21 CFR 862.220 lists the De Novo request content, and 21 CFR 862.230 provides the acceptance review process. The current RTA checklist includes two parts: a required checklist (Appendix A) and a recommended checklist (Appendix B). With this new regulation, almost all the elements from Appendix A and Appendix B are now required elements. Specifically, the new checklists add items such as prior submission, classification summary (eligibility analysis), and device labeling. The FDA will perform an acceptance review within 15 days of receipt. The file is automatically accepted if the acceptance review is not performed.
- Classification Procedure. The FDA aims to meet three goals when reviewing a De Novo request: (1) determining if the probable benefits outweigh the probable risk, (2) identifying probable risks to health for the device/product, and (3) based on the risks to health, determining the level of regulatory controls needed to mitigate the risk. If the FDA concludes that either general controls or both general and special controls will provide a reasonable assurance of safety and effectiveness, a De Novo request will be granted. The entire review will take 150 FDA days, a performance goal set by MDUFA IV, which is different than the statutory deadline of 120 FDA days.
- Premarket Manufacturing Inspection. The final rule gives the FDA a new authority to conduct premarket manufacturing inspection, codified in 21 CFR 860.240. The FDA clarifies that the inspection will only affect “a small percentage” of De Novo requests and is limited to (1) data integrity concerns and (2) quality system regulation when devices have critical or novel manufacturing processes that may affect the safety and effectiveness of the product. For example, if a device proposes to use a novel sterilization technique, the FDA might want to inspect the facility to understand how the sterilization process functions. The sponsors will receive notification prior to any inspections with no specific timeframe.
- Marketing Language. It is important to remember that a De Novo request is not a premarket approval (PMA) and is not subject to the same approval requirements as in a PMA. The FDA recommended De Novo marketing language includes “granted De Novo,” “De Novo is granted,” or “granted marketing authorization.” Similar to other non-PMA devices, the FDA does not recommend “FDA approved” for De Novo devices.