tion of each step in a controlled manufacturing process. The 1987 FDA Guideline on General Principles of Process Validation defines process validation as “establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes” (FDA, 1987, p. 4). A manufacturer carries out this validation through careful documentation of all aspects of the manufacturing process, and it is overseen and deemed acceptable or unacceptable by FDA. The Institute of Medicine (IOM) committee could not itself validate the manufacturing process, nor was the committee in a position to second-guess FDA’s inspection and determination of validity. The committee could, however, review and evaluate the process by which BioPort was working to validate the manufacturing process for AVA.

The committee took the following approach to evaluating BioPort’s validation process. The committee requested from BioPort copies of the Form FDA 483s (Form FDA 483 is a list of observations provided by an FDA investigator at the conclusion of an inspection) from FDA inspections conducted since 1998, as well as BioPort’s responses to these inspection reports. The committee was specifically interested in the subset of materials focusing on product characterization and process validation.

BioPort provided these documents, as well as copies of the MBPI strategic plan with updates. The documents provide detailed information about the responsiveness of the company to the FDA’s findings and the FDA’s evaluations of the manufacturer’s progress.

REGULATORY OVERSIGHT OF VACCINE MANUFACTURE

All vaccines are regulated by FDA’s Center for Biologics Evaluation and Research (CBER). As with other biologics, the development of a new vaccine involves preclinical research (before administration of a vaccine to humans), research in studies with humans in which the product is administered under limited study conditions, an application for licensure, and continued monitoring after licensure and marketing.

The application for licensure must be approved by FDA, which reviews the results of clinical trials and other data and information on safety and efficacy. FDA also reviews detailed information on the manufacturing process and the facility where the product will be produced and tests the products. Previously, sponsors of new biological product applications were required to apply separately for approval of the product and approval of the manufacturing facility (Product License Application and Establishment License Application, respectively), but in 1999 the regulations were modified to combine the two into a single Biologics License Application (BLA) for all products licensed by CBER.



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