The use of the enzyme chitosanase to enable vaccine potency determination in a formulation containing the adjuvant chitosan.

For any pharmaceutical, in development or at the commercial stage, it is critically important that appropriate analytical methodology accompany the product ensuring its safety and efficacy upon release. For vaccines, one of the principal analytical tests is the potency assay, which aims to be predictive of the level of protection seen upon administration. Developing an assay that can measure the potency of a complex drug product formulation can often be challenging due to interference with excipients, most notably adjuvants. Here we present a potency assay developed for a Human Papillomavirus (HPV) vaccine that saw significant interference with the introduction of the adjuvant chitosan. When more traditional means of eliminating interference failed, the enzyme chitosanase was introduced to cleave the adjuvant and rescue the ability to accurately measure potency. When contaminating proteases were observed in a commercial source of chitosanase, an internal effort to supply recombinantly expressed E. coli chitosanase was initiated. This resulted in a pure, active, and consistent supply of chitosanase. These efforts resulted in a robust analytical method that could be used to determine HPV potency in the presence of chitosan. The successful development of this potency assay demonstrates an approach for overcoming interference from adjuvants that may be able to be applied more widely to complex drug product formulations where analytical interference is observed.