Forum 03/09/2007

“Characterization & Comparability of Gardasil®, a Recombinant HPV Vaccine”

Michael W. Washabaugh, Ph.D. – Merck Research Laboratories

The analytical characterization of a recombinant protein-based human papillomavirus (HPV) vaccine is outlined in this presentation. The characterization of a recombinant protein pharmaceutical requires the application of extensive analytical procedures to the product, and the characterization data set is included in regulatory filings to demonstrate understanding of the product.  A comprehensive characterization data set is important for supporting selection of the potency assay, justifying specifications for the product and the impurity profile, characterizing the process, and establishing the “historical” comparability and therapeutic / clinical equivalence of the product in the event of process or facility changes.  Focused testing (rather than testing to infinity) is desired, and investigators are expected to:  identify assays that maximize the potential of detecting differences in quality attributes (ICH Q5E); determine that higher-order structure (secondary, tertiary and quaternary structure) is maintained in the product (ICH Q5E & Q6B);  rationalize the relevance of the microheterogeneity that newer techniques are detecting (ideally compared to clinical lots); and (for vaccines) characterize the adjuvant & adjuvant-antigen complex (EMEA guideline).  For this vaccine, analytical characterization was prioritized to evaluate changes in the immunogenicity / antigenicity, aggregation, primary sequence and post-translational modifications, and impurity profile.