The de novo medical device process is a little-used but potentially valuable means of securing approval for your medical device. The pathway was established in 1997 subject to the Federal Food Drug & Cosmetic Act, Section 513 (f) (2). It was designed to employ a risk-based strategy for novel devices that have not yet been classified. Basically, it establishes a new device type including classification, regulation, appropriate controls and product code. The device then becomes eligible to act as a predicate for new medical devices. The following describes the origins of the de novo process, how the submission process works and its potential advantages.

The medical device approval process for new devices was addressed in 1976, establishing new devices that are not equivalent to a Class I or Class II device becomes a new Class III device. The Medical Device Exemptions law Section 513 promulgated in 1976, provides for the following for the classification of devices based on a risk-based approach, with Class I applying to the least complex and risky devices:

• 513(a)(1)(A): Class I, “General Controls”
• 513(a)(1)(B): Class II, “Special Controls”
• 513(a)(1)(C): Class III, “Premarket Approval”
  
  

A word about general and special controls: devices are classified according to the degree of difficulty in assuring their safety and effectiveness. Class I, which is synonymous with General Controls, is the least stringent of the three device classes provided in the Amendments. Before placing a device in Class I, FDA must determine that there is sufficient information available to support such a classification decision. Second, FDA must decide that the General Controls are sufficient to provide reasonable assurance of the device's safety and effectiveness. Class I devices are not subject to the restrictions of Class II - Special Controls or Class III - Premarket Approval. Class I devices are not intended for use in supporting or sustaining life or to be of substantial importance in preventing impairment to human health, and they may not present a potential unreasonable risk of illness or injury. Unless otherwise exempted, the General Controls provisions of the Amendments are applicable to all devices regardless of their classification status.

Section 513 (a) (1) (C) provides that Class III devices (highest risk) require Premarket Approval, with appropriate stringent controls for safety. Section 513 (f) (1) addresses new devices, which are termed post-amendment Class III devices. A device that is not equivalent to a Class I or II device is classified into Class III, as a new device. The application process involves the submission by the manufacturer of a pre-market notification. FDA’s Center for Devices and Radiological Health (CDRH) decides whether the product is not substantially equivalent because no predicate device exists. If no predicate device exists, the manufacturer then submits the De Novo application. FDA then determines whether to classify the device from Class III to Class I or Class II.

A change in the de novo process came about as a result of the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012, which allowed for an alternative process as prescribed by (Section 513 (f) (2) of the FD&C Act. This pathway does not require submission of a 510 (k) prior to a de novo submission, which was the case before 2012. The review time was set at four months. In this iteration of the de novo process, the manufacturer submits a de novo application, and CDRH decides whether to classify the device from Class III to Class I or Class II with a new classification. The 2017 De Novo guidance also provides for a pre-submission meeting opportunity with FDA for manufacturers, a useful benefit for manufacturers. It allows applicants to pose questions about their product and get feedback from FDA. It also opens up a line of communication between the manufacturer and the CDRH review team, which can save the applicant significant time and money.

The mechanism provides two options. An applicant can file a 510 (k) clearance submission and then apply for de novo, a pathway that is useful in the event a predicate device exists. Alternatively, it can apply for direct de novo, usually after a pre-submission meeting with CDRH.

Under the first option, FDA reviews the 510 (k) and makes a “Not Substantially Equivalent” (NSE) determination due to the absence of a predicate device (this means that the proposed predicate device does not have the same intended use or characteristics of the sponsor’s device). FDA may indicate in its NSE letter that the new device could be an appropriate de novo candidate based on its risk/benefit profile.

The sponsor then submits the de novo application, addressing additional evidence that demonstrates the safety and effectiveness of the new device. The applicant should also address any differences and gaps in evidence between the 510 (k) and the de novo applications, including a safety and efficacy profile as well as any needed additional testing requirements. FDA will then review the materials, and may ask for additional information before deciding whether to approve or deny the submission.

Under the second option (direct de novo), CDRH will review the application without need of a 510 (k) submission. The ideal circumstances for a De Novo application are situations where there is an absence of a predicate, something with which the FDA must agree, and where the applicant believes that the device is more properly classified as either Class I or Class II. The first step in this pathway is the submission of the de novo application, along with evidence that establishes safety. The information needed for the submission is similar to that required in a 510(k) application:

• A device description is required
• Labeling must be established
• Performance testing must take place
  
  

In addition, risks to health and safety must be addressed. The applicant must show how mitigation of risk is to be achieved, and explain why the device does not fit into the 510 (k) or PMA categories. If Class II is the objective, then special controls must be identified, in order to mitigate risks.

At this point, FDA reviews the de novo submission. CDRH sometimes consults with the applicant before deciding whether to grant or deny approval. This is where a pre-submission meeting is useful. By interacting with FDA before the application is submitted, the chances for approval are enhanced. Approval prospects are also dependent upon the manufacturers’ accurate definition of the product’s intended use and design, and its presentation of safety and effectiveness data.

Assuming approval is granted, after gaining de novo approval the sponsor must make sure the device is legally marketed and sold. The device will then serve as a predicate for other devices. FDA will publish an order describing controls and the new classification, as well as a summary of its decision.

Applicants should ensure that they present a convincing case in favor of the de novo application. The device description and intended must be accurate, the necessary performing testing requirements must be complete and any required clinical testing must be performed. As noted, manufacturers should use the pre-submission process to save time and money, and build a relationship with the FDA review team.

In sum, de Novo is a viable path for some manufacturers, and it should be considered as one of the pathways for securing FDA clearance for your product. If you would like additional information or assistance in submitting a de novo request, please contact Mark Mansour ([email protected]or 202-906-8691) or your Dykema relationship attorney.