In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.
"Should I pursue a de novo classification for my medical device?" "Is the de novo pathway the right regulatory pathway for my medical device submission?"
If you're asking these questions, you're not alone. Unsurprisingly, the most common answer I give clients who ask me these question is, “It depends." That answer also happens to be one of the top most annoying responses to hear from a regulatory consultant. So, I typically like to follow it up with, "Tell me more about your device, your competitors, and the current standard of care, and let's figure out if the de novo pathway is right for you!"
The best way to approach this decision is probably to understand how and why the de novo classification came to be. Prior to the 1997 Food and Drug Administration Modernization Act (FDAMA), the de novo pathway didn't exist. Until then, devices that received an NSE (not substantially equivalent) determination in response to a premarket notification [510(k)] submission were automatically deemed Class III. Class III devices are those considered high risk, therefore requiring the often lengthier Premarket Approval (PMA) process: this new de novo process was designed to usher through any new device that was both 1) unprecedented (novel), and 2) low to moderate risk (or with risk that was easily mitigated). It excluded devices that had already been put into Class III, but it offered a four step automatic reclassification process for novel devices using a risk-based strategy.
The 4-step process consists of: (1) the sponsor submitting a premarket notification [510(k)], (2) FDA making a Not Substantially Equivalent (NSE) decision due to lack of predicate, (3) the sponsor submitting a de novo application, and (4) FDA reviewing the application and making a final decision to approve or deny it.
This process was streamlined in 2012 when FDA further modified the FD&C Act under the Food and Drug Administration Safety and Innovation Act (FDASIA) to, in their words, "allow a sponsor to submit a de novo classification request to the FDA for novel low to moderate risk devices without first being required to submit a 510(k)." They added a more efficient, two-step, automatic reclassification process consisting of just the last two steps of the four-step process outlined above. This allows 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 relevant information recommended for a 510(k) submission. Also keep in mind that the de novo application should sufficiently address the characterization of all health risks of the device, as well as how those risks might be mitigated. FDA will then review the application, and may work with the sponsor to get more information. If FDA grants the decision, the device can be legally marketed and the new classification (and any applicable special controls) will be published in the Federal Register Notice.
In short, 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 costly, lengthy PMA. A de novo classification for your device may then 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.
One more thing to keep in mind: FDA strongly encourages a Pre-Submission (Pre-Sub) to informally request guidance on a novel device. However, a sponsor should only submit a Pre-Sub for a de novo application after the device design and intended use are established. It's also recommended that the sponsor have adequate information collected regarding the safety and effectiveness of the device.
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 aims to have a decision to you within 60 days. 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.
It's never been easier to do so, as in recent years the number of successful submissions has increased, and information about them has become more accessible:
Second, check out the FDA de novo classification process guidance document and read the FDA guidance on determining benefit-risk factors.
Additionally, in 2010 FDA began releasing summary documents for devices classified through the de novo process. The table shown below is featured on FDA's Evaluation of Automatic Class III Designation (de novo) Summaries, where you can read up on devices that have made it through this way.