When FDA added De Novo as an alternative pathway for medical device manufacturers seeking Class I or Class II classification of their novel products in 1997, the option wasn’t terribly well received. Even though novel medical device products are automatically classified as a Class III device—meaning extensive safety studies, risk mitigation and efficacy analysis is required when seeking FDA approval—the alternative of a De Novo request was not originally viewed as a viable option to streamline the bureaucratic challenges posed to firms seeking a pre-market clearance of their devices.

The FDA’s initial De Novo process retained the cumbersome application requirements whereby firms were first to submit a full 510(k) application and then wait for a rejection of that application by the agency based on “Not Substantially Equivalent” (NSE) before resubmitting under De Novo and seeking a determination of a newly classified device that should be considered low risk, the lengthy, unpredictable and expensive process proved to be a daunting challenge of little utility to the device industry.

Fortunately, under the FDA’s new age of efficient and effective regulation designed to make advancements in healthcare and accessibility easier without sacrificing safety and quality, a new approach to the De Novo application has been instituted. The FDA has simplified the De Novo review process, clarified when a device concept fits the program parameters and refined the required data inputs, per an October 17, 2017 guidance called De Novo Classification Process. Sponsors who can demonstrate that their novel product, for which there is no one-to-one precedent or predicate device, or where it does not meet the requirements of a Class III medical device can request a “down-grade” to a Class I or Class II, without first submitting a 510(k) application. The FDA has 120 days to review and classify the device, provided the submission and backup documentation are acceptable.

Devices Defined

FDA’s definition of medical devices covers everything from toothbrushes and sterile bandages to contact lenses and condoms to HIV test kits and heart stents, so there is a wide range of potential consumer risk as well as reliance on the device for medical benefit. FDA has established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialties, each assigned to one of three classifications (Class I, II, III) based on the level of control necessary to assure its safety and effectiveness.¹

• Class I: The most basic and appropriate for items such as tongue depressors, which would cause minimal harm, require only general safety controls. In fact, 95% of these basic Class I devices are entirely exempt from the pre-market regulatory approval process.²
• Class II: Device examples being acupuncture needles and surgical drapes, are held to a higher safety standard than general controls alone, requiring additional special controls. The majority of medical devices are considered Class II.
• Class III: Devices require general and special controls as well as premarket approval, which encompasses a scientific review of the device’s safety and effectiveness. Examples of Class III devices are automatic defibrillators and implantable pacemakers.

De Novo and the Simplified Pathway

De Novo applications are appropriate in cases where it appears that the device meets the statutory standards for classification into Class I or Class II under section 513(a)(1) of the Food Drug & Cosmetic Act, and when the sponsor has determined that the device does not fall within any existing classification regulation (ie., there is no clear predicate device and/or the device has received a non-substantial equivalent (NSE) determination on an earlier 510(k) submission).

Although Class I and Class II devices are not subject to the same stringent controls of Class III devices, submitters must still present a complete picture of the probable risks and benefits of the device as well as how to mitigate risks through general and/or special controls.

Once a De Novo is granted, the device may be marketed immediately as FDA will create a classification regulation and permit the device to serve as a predicate for future 510(k) applications. The classification will be published in the Federal Register, along with the controls necessary to provide reasonable assurance of safety and effectiveness (General for Class I, or General and Special for Class II).

If the De Novo request is declined, the device remains as a Class III and may not be marketed without further efforts by the sponsor and acceptance by FDA.

Pre-Subs: A First Step in a Successful De Novo Submission

As previously stated, the FDA data requirements and safety concerns for Class I and Class II medical devices is considered to have a “lower threshold” than their Class III counterparts; however, submitters should never take for granted the importance of their De Novo request or the completeness of the information in the packet. In some cases, firms may wish to secure the services of a third-party reviewer to provide comment on the submission prior to submitting to FDA. These reviews can be especially helpful in cases of a first-time sponsor or when the there is a question as to whether the data submitted fully addresses any consumer risks.

FDA offers an opportunity for submitters to file a “Pre-Sub”, or early submission allowing for agency feedback on whether a device may be eligible for the De Novo classification process, including whether a potential predicate device exists. The agency can also confirm required evidence including study data necessary to support the De Novo request. A Pre-Sub is strongly encouraged, particularly in cases where the device was not previously reviewed under an earlier 510(k).

Pre-Sub submissions should include the proposed classification for the device and why general and/or special controls are adequate to reasonably assure safety and effectiveness. It should also contain search results, including search terms, demonstrating that there is no like legally marketed device and no appropriate device classification. A rationale of why the device does not fit into any other identified classification should also be included. FDA will review the Pre-Sub and their valuable feedback will help determine a path forward as well as items are needed to improve the submission.

By some estimates it can take three to seven years to bring a medical device to market in the United States, including safety studies, FDA reviews and sponsor application revisions. The option for a less stringent De Novo application, in cases where appropriate, can be an alternate and speedier pathway bringing the benefits of a novel product with low risk to the consumer to market. To assess the viability of your product in this unique submission area, contact a regulatory expert with a strong track record in medical device submissions or contact the FDA directly, and the earlier in the process the better. A solid foundation can increase the chances of a successful submission and get your medical device to market more quickly.

References

1. FDA. “Classify Your Medical Device”. Accessed March 23, 2018 Retrieved from https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/default.htm
2. FDA. “Learn if a Medical Device Has been Cleared by FDA for Marketing”. Accessed March 23, 2018. Retrieved from https://www.fda.gov/MedicalDevices/ResourcesforYou/Consumers/ucm142523.htm