BUSINESS OVERVIEW 6 trial in support of a 510(k) submission. A manufacturer that maintenance of complaint and related investigation files, and wishes to conduct a clinical stu trial dy involving the device is other quality assurance controls during the manufacturing subject to the FDA’s IDE regulation. The IDE regulation process; distinguishes between significant and non-significant risk device • unannounced routine or for-cause inspections by the FDA, studies and the procedures for obtaining approval to begin the which may include suppliers’ facilities; study differ accordingly. A significant risk device presents a potential for serious risk to the health, safety, or welfare of a • advertising and promotion regulations, which prohibit the subject. Significant risk devices are devices that are substantially promotion of products for uncleared or unapproved or “off- important in diagnosing, curing, mitigating, or treating disease label” uses and impose other restrictions on advertising and or in preventing impairment to human health. Studies of devices labeling; that pose a significant risk require both FDA and an IRB approval • post-approvalrestrictions or conditions, including prior to initiation of a clinical trial. Non-significant risk devices are requirements to conduct post-market surveillance studies to devices that do not pose a significant risk to the human subjects. establish continued safety data or tracking products through A non-significant risk device study requires IRB approval prior the chain of distribution to the patient level; and to initiation of a clinical trial, and FDA approval of the study is • compliance with the regulations requiring the reporting of deemed to be in effect if certain conditions are met. adverse events and certain device malfunctions to the FDA. An IDE application must be supported by appropriate data, The failure to comply with applicable regulatory requirements can such as animal and laboratory testing results, showing that it is result in enforcement action by the FDA, which may include any of safe to test the device in humans and that the testing protocol is the following sanctions: scientifically sound. An IDE application is considered approved • untitled letters, warning letters, fines, injunctions or civil 30 days after it has been received by the FDA, unless the FDA penalties; otherwise informs the sponsor prior to 30 calendar days from the date of receipt, that the IDE is approved, approved with • recalls, detentions or seizures of products; conditions, or disapproved. IDE approval permits a specified • operating restrictions; number of subjects to be enrolled at specified study centers. The • delays in the introduction of products into the market; clinical trial must be conducted in accordance, and FDA approval of the study is deemed to be in effect if certain conditions are met. • total or partial suspension of production; with applicable regulations, including, but not limited to, the FDA’s • delay or refusal of the FDA or other regulators to grant 510(k) IDE regulations and GCP. The investigators must obtain subject clearance or PMA application approvals of new products; informed consent, rigorously follow the investigational plan and • withdrawals of 510(k) clearance or PMA application approvals; study protocol, control the disposition of investigational devices, or and comply with all reporting and record keeping requirements. A clinical trial may be suspended or terminated by the FDA, the • criminal prosecution. IRB or the sponsor at any time for various reasons, including a Review and Approval of Combination Products in the United States determination that the risks to the study participants outweigh Certain products may be comprised of components that would the benefits of participation in the trial. Approval of an IDE does normal ly be regulated under different types of regulatory not bind the FDA to accept the results of the trial as sufficient to authorities, and frequently by different Centers at the FDA. prove the product’s safety and efficacy, even if the trial meets its These products are known as combination products. Specifically, intended success criteria. under regulations issued by the FDA, a combination product may Post-Approval Regulation of Biological Products and Medical be: Devices in the United States • a product comprised of two or more regulated components After a biological product or device is placed on the market, that are physically, chemically, or otherwise combined or mixed numerous regulatory requirements apply including, but not and produced as a single entity; limited to: • two or more separate products packaged together in a single • submitting and updating establishment registration and device package or as a unit and comprised of drug and device products; listings with the FDA; • a drug or device packaged separately that according to its • compliance with the manufacturing regulations and standards, investigational plan or proposed labeling is intended for use including cGMP, for biological products, and the QSR, which only with an approved individual ly specified drug or device require device manufacturers to fol low stringent design, where both are required to achieve the intended use, indication, testing, control, documentation, record maintenance, including or effect and where upon approval of the proposed product the 96 – GENSIGHT BIOLOGICS – 2017 Registration Document