Representatives from the newly formed Division of Industry and Consumer Education (DICE, formerly DSMICA) state that this is the most common question they receive regarding the de novo process. Not surprisingly, the answer you’ll likely receive from DICE is: “It depends.”
Prior to 1997 and the Food and Drug Administration Modernization Act (FDAMA), any new device that didn’t fall under a specific classification was deemed Class III (see Food Drug & Cosmetic Act (FD&C Act) Sections 513(a)(1)(C) and 513(f)(1)). Class III devices are considered “high risk” and therefore require the often lengthier Premarket Approval (PMA) process. In 1997, FDAMA modified the FD&C Act to include a new de novo classification process (see FD&C Act Section 513(f)(2)). While this process excluded devices already classified into Class III, it allowed a 4-step automatic reclassification process for novel devices using a risk-based strategy. In other words, if you have a novel technology that isn’t considered high risk (or if the risks can be adequately mitigated) you might be able to get on the market without a PMA. This can mean less time, and less money, on your pathway to market. While you may pave the way for other companies to use your device as a predicate, you will have helped decide the regulatory requirements for future clearances and have the “first-to-market” claim with your technology.
In June 2014 FDA granted the de novo application for the ReWalk™ Personal Exoskeleton System to enable individuals with Spinal Cord Injury (SCI) to stand upright and walk
In 2012, FDA further modified the FD&C Act under the Food and Drug Administration Safety and Innovation Act (FDASIA). In this revision, they added a 2-step automatic reclassification process with the goal of increasing efficiency and streamlining the de novo process. The 4-step process consists of: (1) the sponsor submits a premarket notification (510(k)), (2) FDA makes a Not Substantially Equivalent (NSE) decision due to lack of predicate, (3) the sponsor submits a de novo application, and (4) FDA reviews the application and makes their final decision to “grant” or “decline” it. The newer 2-step process consists of just the last two steps of the 4-step process, allowing the sponsor to skip the 510(k) and NSE decision. However, the de novo application in both processes should either refer to a previous 510(k) or include all the pertinent information recommended for a 510(k) submission. Similarly, the de novo application should adequately address the characterization of all health risks of the device and how the risks might be mitigated. FDA will then review the application and may interact with the sponsor to ask for additional information. Ultimately, FDA will make their final decision: if granted, the device can be legally marketed and the new classification (and any applicable special controls) will be published in the Federal Register Notice.
The de novo application for the Cerena TMS to treat migraine headaches was granted to eNeura Therapeutics in December 2013
FDA strongly encourages a Pre-Submission (Pre-Sub) to informally request guidance on a novel device. A sponsor should only submit a Pre-Sub for a de novo application after the device design and intended use are established. It is also preferred that the sponsor have sufficient information collected regarding safety and effectiveness of the device. When deciding whether the de novo pathway is right for your company, be sure to do your homework and regulatory research to show that your device is de novo eligible. You should make sure that your new device is not already classified by researching the available FDA databases (510(k), PMA, Product Classification) and prior FDA decisions. If you can submit an acceptable de novo application where the necessary performance testing is completed, the risks to health have been mitigated, and the special controls have been identified, then FDA hopes to have a decision to you within 60 days. Be on the lookout for an FDA guidance document regarding the de novo process in the near future. This guidance should include more details on the submission content and timeline of the process. While FDA has granted roughly 50 de novo applications since 1997, the number has been steadily increasing over the past few years as the process becomes easier to navigate.
Evaluation of Automatic Class III Designation (De Novo) Summaries
Draft Guidance for Industry and Food and Drug Administration Staff – De Novo Classification Process (Evaluation of Automatic Class III Designation)
Guidance for Industry and Food and Drug Administration Staff – Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approvals and De Novo Classifications