Several types of premarket submissions can be made to FDA. In order to legally market a device in the US, the most common forms of premarket submissions to FDA are the 510(k) premarket notification submission and the PMA premarket approval. Another lesser known premarket submission is the de novo submission. Each of these submission types result in a determination by FDA that clears [510(k)], approves [PMA], or grants [de novo] marketing rights to the successful submitter. Other submissions to FDA include Pre-submissions (Pre-subs), Investigational Device Exemptions (IDE), Humanitarian Device Exemptions (HDE), and Master Files, to name a few. The most commonly made submissions are described in more detail below.
Each person who wants to market in the U.S., a Class I, II, and III device intended for human use, for which a Premarket Approval (PMA) is not required, must submit a 510(k) submission to FDA unless the device is exempt from 510(k) requirements of the Federal Food, Drug, and Cosmetic Act (the Act) and does not exceed the limitations of exemptions in part .9 of the device classification regulation chapters (e.g., 21 CFR 862.9, 21 CFR 864.9). A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective (substantially equivalent) to a legally marketed device that is not subject to PMA. Submitters must compare their device to one or more similar legally marketed devices (predicates) and make and support their substantial equivalency claims. Until the submitter receives an order declaring a device SE, the submitter may not proceed to market the device. Once the device is determined to be SE, it can then be marketed in the U.S.
Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices, and the most stringent of the device marketing applications. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. Due to the level of risk associated with Class III devices, FDA has determined that general and special controls alone are insufficient to assure the safety and effectiveness of Class III devices. Therefore, these devices require a premarket approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing clearance. Please note that some Class III preamendment devices may require a Class III 510(k). PMA applications will include technical sections, usually divided into non-clinical laboratory studies and clinical investigations. PMA approval typically requires a facility inspection to confirm compliance to 21 CFR 820 prior to approval.
The de novo pathway for device marketing rights was added to address novel devices of low to moderate risk that do not have a valid predicate device. Upon successful review of a de novo submission, FDA creates a classification for the device, a regulation if necessary, and identifies any special controls required for future premarket submissions of substantially equivalent devices. Companies with novel devices of low to moderate risk have two options when considering the de novo pathway: the company can submit a 510(k) to the FDA, and upon receipt of a “Not Substantially Equivalent” determination, the de novo request can be made; or the company can submit a de novo request without first submitting a 510(k). Devices that are classified through the de novo process may be marketed and used as predicates for future 510(k) submissions.
Pre-submissions are made to the FDA in order to request FDA feedback. Pre-subs are used for various reasons including meeting requests, to study risk determination, for submission issues, and for FDA feedback to specific questions related to a pending submission or protocol. The main purpose of the Pre-Sub Program (previously known as the Pre-IDE Program) is to provide the opportunity for a sponsor to obtain FDA feedback prior to an intended submission of an IDE or marketing application. The Pre-Sub Program can also provide a mechanism for the Agency to provide advice to sponsors who are developing protocols for clinical studies for which an IDE would not be required, such as studies of non-significant risk (NSR) devices or for clinical studies conducted outside of the U.S. to support future U.S. marketing applications. Consequently, the Pre-Sub program can provide an efficient path from device concept to market while facilitating the agency’s goal of fostering the development of new medical devices.