9 Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successful f ly within any specified period, if at all. The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subj u ects or patients are being exposed to an unacceptabl a e health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug r or biologic has been associated with unexpected serious harm to patients. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether a trial may move forward at designated check points based on access to certain data from the trial. Concurrent with clinical trials, companies usually complete additional animal stud t ies and also must develop additional information about the chemistry r and physical characteristics of the drug r or biologic as well as finalize a process for manufact f ur t ing the product in commercial quantities in accordance with cGMP requirements. The manufac f turing process must be capa a bl a e of consistently producing quality batches of the product and, among other things, companies must develop methods for testing the identity, strength, quality and purity of the final product. Additionally, appropriate packaging must be selected and tested and stability studi t es must be conducted to demonstrate that our product candidates do not undergo unacceptabl a e deterioration over their shelf life. f NDA/B A LA B Review Process Following completion of the clinical trials, data are analyzed to assess whether the investigational produc d t is safe and effe f ctive for the proposed indicated use or uses. The results of preclinical studi t es and clinical trials are then subm u itted to the FDA as part of an NDA or BLA, along with proposed labe a ling, chemistry r and manufact f ur t ing information to ensure product quality and other relevant data. In short, the NDA or BLA is a request for approval to market the drug r or biologic for one or more specified indications and must contain proof of safety and effi f cacy for a drug r or safety, purity and potency for a biologic. The application may include both negative and ambiguous results of preclinical studi t es and clinical trials, as well as positive findings. Data may come from company-sponsored clinical trials intended to test the safety and effi f cacy of a product’s use or from a number of alternative sources, including studi t es initiated by investigators. To suppor u t marketing approval, the data subm u itted must be sufficient in quality and quantity to establ a ish the safety and effi f cacy of the investigational product to the satisfaction of FDA. FDA approval of an NDA or BLA must be obtained before a drug r or biologic may be marketed in the United States. Under the Prescription Drug r User Fee Act, or PDUFA, as amended, each NDA or BLA must be accompanied by a user fee. The FDA adju d sts the PDUFA user fees on an annual basis. PDUFA also imposes an annual program fee for approved human drugs r and biologics. Fee waivers or reductions are availabl a e in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Additionally, no user fees are assessed on NDAs or BLAs for products designated as orpha r n drugs r , unless the product also includes a non-orpha r n indication. The FDA reviews all subm u itted NDAs and BLAs before it accepts them for filing, and may request additional information rather than accepting the NDA or BLA for filing. The FDA must make a decision on accepting an NDA or BLA for filing within 60 days of receipt. Once the subm u ission is accepted for filing, the FDA begins an in-depth review of the NDA or BLA. Under the goals and policies agreed to by the FDA under PDUFA, the FDA has ten months, from the filing date, in which to complete its initial review of a new molecular-entity NDA or original BLA and respond to the applicant, and six months from the filing date of a new molecular-entity NDA or original BLA designated for priority review. The FDA does not always meet its PDUFA goal dates for standard and priority NDAs or BLAs, and the review process is ofte f n extended by FDA requests for additional information or clarific f ation.