Validation of assays for use with combination vaccines

A general methodology is presented for the validation of assays used for te sting combination vaccines. The presentation is detailed and technical as o ur intention is to address challenges that we have encountered in the desig n and statistical analysis of assay validation studies. There are several n oteworthy features which render the approach particularly useful in practic e. It employs a statistical experimental design approach to the investigati on of assay ruggedness with respect to manufacturing variability; it makes use of the assay variability results to determine the level of test-run rep lication necessary to achieve precision compatible with the product specifi cations; and, it provides a generic approach to assay validation. With combination vaccines, as with other pharmaceuticals, the analytical me thods for release and stability must be validated early in the development programme Several things, though, distinguish this task with combination va ccines: (1) assays are typically pre-existing and often have been validated for use with an established sample matrix, e.g, a monovalent formulation; (2) sample matrices are complex and therefore more subject to manufacturing variability and more likely to cause assay interferences; and (3) the anal ytical workload is considerable due to the number of antigens. The methodology presented here was developed jointly by Merck Research Labo ratories (West Point, PA) and Pasteur Merieux Connaught, Inc. (Swiftwater, PA). Many of the issues discussed here have application outside of combinat ion vaccines and are common features of all assay validations. (C) 1999 The International Association for Biologicals.