BUSINESS OVERVIEW 6 exclusive use of the reference biologic. However, complexities reasonable assurance of the devices’ safety and effectiveness. associated with the larger and often more complex structure of Premarket review and clearance by the FDA for Class I I devices biological products, as well as the process by which such products are accomplished through the 510(k) premarket notification are manufactured, pose significant hurdles to implementation procedure, although some Class I I devices are exempt from the that are still being worked out by the FDA. 510(k) requirements. Premarket notifications are subject to user Review and Approval of Medical Devices in the United States fees, unless a specific exemption applies. Medical devices in the United States are strictly regulated by Class I I I devices are deemed by the FDA to pose the greatest the FDA. Under the FD&C Act, a medical device is defined as an risk, such as those for which reasonable assurance of the device’s instrument, apparatus, implement, machine, contrivance, implant, safety and effectiveness cannot be assured solely by the general in vitro reagent, or other similar or related article, including a controls and special controls described above and that are life- component part, or accessory which is, among other things: sustaining or life-supporting. A PMA application must provide intended for use in the diagnosis of disease or other conditions, valid scientific evidence, typically extensive preclinical and clinical or in the cure, mitigation, treatment, or prevention of disease, in trial data and information about the device and its components man or other animals; or intended to affect the structure or any regarding, among other things, device design, manufacturing and function of the body of man or other animals, and which does not labeling. PMA applications (and supplemental PMA applications) achieve its primary intended purposes through chemical action are subject to significantly higher user fees than are 510(k) within or on the body of man or other animals and which is not premarket notifications. dependent upon being metabolized for the achievement of any 510(k) Premarket Notification of its primary intended purposes. This definition provides a clear To obtain 510(k) clearance, a manufacturer must submit a distinction between a medical device and other FDA regulated premarket notification demonstrating that the proposed device products such as drugs. If the primary intended purpose of is “substantial ly equivalent” to a predicate device, which is a the product is achieved through chemical action or by being previously cleared 510(k) device or a pre-amendment device metabolized by the body, the product is regulated as a drug or that was in commercial distribution before May 28, 1976, biological product. for which the FDA has not yet cal led for the submission of a Unless an exemption applies, a new or modified medical device PMA application. The FDA’s 510(k) clearance pathway usually may not be marketed in the United States unless and until it has takes from three to 12 months from the date the application is been cleared through filing of a 510(k) premarket notification, submitted and filed with the FDA, but it can take significantly or 510(k), or approved by the FDA pursuant to a Premarket longer and clearance is never assured. The FDA has issued Approval, or PMA, application. The information that must be guidance documents meant to expedite review of a 510(k) and submitted to the FDA in order to obtain clearance or approval facilitate interactions between applicants and the agency. To to market a new or modified medical device varies depending on demonstrate substantial equivalence, a manufacturer must show how the medical device is classified by the FDA. Medical devices that the device has the same intended use as a predicate device are classified into one of three classes on the basis of the controls and the same technological characteristics, or the same intended deemed by the FDA to be necessary to reasonably ensure their use and different technological characteristics and is as safe safety and effectiveness. and as effective as the predicate device and does not raise new questions of safety and effectiveness than the predicate device. Class I devices are low risk devices for which reasonable assurance Most 510(k)s do not require clinical data for clearance, but the of safety and effectiveness can be provided by adherence to the FDA’s general controls for medical devices, which include FDA may request such data. The FDA seeks to review and act applicable portions of the FDA’s Quality System Regulation, or on a 510(k) within 90 days of submission, but it may take longer QSR, facility registration and product listing, reporting of adverse if the agency finds that it requires more information to review medical events and malfunctions and truthful and non-misleading the 510(k). If the FDA determines that the device is substantially labeling. Many Class I devices are exempt from premarket equivalent to a predicate device, the subject device may be regulation; however, some Class I devices require premarket marketed. However, if the FDA concludes that a new or modified clearance by the FDA through the 510(k) premarket notification device is not substantially equivalent to a predicate device, the process. new or modified device wil l be classified in Class I I I and the manufacturer wil l be required to submit a PMA application to Class I I devices are moderate risk devices and are subject to market the product. Devices of a new type that the FDA has not the FDA’s general controls, and any other special controls, previously classified based on risk are automatical ly classified such as performance standards, post-market surveil lance and into Class I I I by operation of the FD&C Act, regardless of the FDA guidelines, deemed necessary by the FDA to provide level of risk they pose. To avoid requiring PMA review of low- to 94 – GENSIGHT BIOLOGICS – 2017 Registration Document