Several types of submissions can be made to FDA, regarding a new or modified medical device being introduced to the US market. In order to legally market a device in the US, the most common forms of market authorization submissions to FDA are the 510(k) premarket notification submission and the PMA premarket approval. Another lesser known premarket submission is the De Novo petition; however, with more novel technologies and new intended uses coming to the device industry, the De Novo pathway is becoming more common. 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), Breakthrough Device Designation Request Q-Submissions, 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. Please contact Ken Block Consulting (KBC) to discuss these FDA submissions and how our team can help you achieve US market introduction for your medical devices.
Each person who wants to market (i.e., promote, advertise, arrange to distribute, etc.) within the US any Class I, II, and III device intended for human use, for which a Premarket Approval (PMA) or De Novo petition 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 notification (a type of US regulatory submission) made to FDA to demonstrate that the device to be marketed/distributed 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 with objective evidence. Until the submitter receives an order declaring a device substantially equivalent (SE), the submitter may not proceed to market or distribute the device. Once the device is determined to be SE, it can then be marketed and distributed in the US.
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 petition, FDA creates a classification for the new device type, a new regulation when 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 petition 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. When the possibility of a De Novo petition exists, conducting a pre-submission to the FDA to discuss the device is highly recommended.
Pre-Submissions are a type of Q-Submission, made to the FDA in order to request FDA feedback on some aspect of a device (where the full US market authorization submission for that device has not yet been submitted to the FDA). 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 US to support future US 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, including those novel devices with a De Novo regulatory pathway.
Breakthrough Device Designation Requests
One special type of Q-Submission is the Breakthrough Device Designation (BDD) Request, intended for those devices addressing a life-threatening or seriously debilitating disease or condition. In essence, the BDD Request is a type of application to the FDA, where the sponsor presents a device with "breakthrough technology" that could increase the Standard of Care (SOC) regarding either the diagnostic or treatment side of the targeted disease or condition. In that BDD application, the sponsor then presents this novel and impactful "breakthrough technology" along with an explanation of device development to date, objective evidence about device performance to date, projected expected final device performance, and projected SOC impact. Against certain evaluation criteria, the sponsor's BDD application is then focused to convince FDA of a "reasonable expectation that the [sponsor] device could function as intended (technical success) and that a functioning [sponsor] device could more effectively treat or diagnose the identified disease or condition (clinical success)." Acceptance into this special program brings several significant advantages, including close collaboration with an assigned FDA review team, quick scheduling of "Sprint Discussion" meetings to resolve various issues quickly with that FDA team, and priority review of the eventual market authorization submission, whether PMA, De Novo or "Breakthrough" 510(k). The KBC team has helped multiple clients achieve Breakthrough Device status for innovative and important new device technologies, including software as a medical device (SaMD). Read about KBC successful BDD submissions for our clients, as well as links to published articles authored by KBC on the Breakthrough Device Program, here.