turing Practices throughout the production process. Validation is a critical component of current Good Manufacturing Practices compliance. Essentially, validation is demonstrating that the manufacturing procedures, tests, equipment, and systems perform as intended and produce the expected and consistent results.
The Office of Establishment Licensing and Product Surveillance within CBER is responsible for the review of vaccine ELAs. The internal review consists primarily of determining that (1) the layout of the manufacturing facilities, the equipment, and the systems are adequate for vaccine production and storage; (2) the expert personnel have been properly trained for their assigned duties and functions; and (3) validation of the equipment, systems, and process controls is satisfactory.
FDA approval for licensure is based on (1) a satisfactory review of all data indicating that the product is safe and effective for its intended use; (2) review and acceptance of the manufacturer's labeling; (3) a satisfactory review of the manufacturer's protocols that summarize the manufacturing and testing on a specified number of vaccine lots to establish the consistency of the process; (4) confirmatory testing by CBER on product samples received from the manufacturer; and (5) a satisfactory FDA inspection of the manufacturer's vaccine production facilities (Hopps et al., 1988).
In November 1992, the FDA published guidelines on cooperative manufacturing for biological products, recognizing four types of manufacturing arrangements: short supply, divided, shared, and contract.
Short supply allows a licensed manufacturer to obtain from an unlicensed facility source materials that are declared to be in short supply. Historically, the short supply provisions are provided under an old FDA regulation that is rarely used today by licensed vaccine manufacturers. Divided manufacturing permits two manufacturers, each licensed to produce the biologic in its entirety, to produce such a product together. Approval of this arrangement requires both manufacturers to file PLA amendments that describe what procedures will be performed at each facility, along with copies of the labeling to be used for the intermediate and finished products. This arrangement is not often used by licensed vaccine manufacturers.
Under a shared arrangement, two or more manufacturers participate in the manufacture of a biological product, with each manufacturer required to hold both an establishment license and a product license for the ingredient that it contributes to the process. However, none of the manufacturers are required to be licensed to perform all steps in the manufacturing process. To qualify for licensure approval, each manufacturer performs significant steps in the manufacture of the active ingredient of the product. Under a shared arrangement, the manufacturer of the final product also has the ultimate responsibility for providing data that demonstrate the potency,