Statistical Methods for Comparability Studies

Abstract

Biological products are complex mixtures of molecular species. Their individual entities are difficult to characterize. During development and post-approval, improvements are made in production methods, process and control test methods for product characterization, and equipment or facilities. These could result in fundamental changes to the biological product itself, perhaps requiring additional clinical studies to demonstrate that the product's safety, identity, purity and potency have not been impacted. Consequently, regulations require the sponsor to demonstrate product comparability between the post-change and pre-change products. A stepwise approach to extensively characterize the post-change product and the pre-change product with state-of-the-art technology is the first step in assessing the potential impact on safety and efficacy. These comparability studies should have direct side-by-side comparisons of the pre-change ``reference{''} product and post-change ``test{''} product. In this chapter, statistical methods are reviewed for establishing comparability in relation to critical quality attributes and animal pharmacokinetics (PK) to systematically evaluate the data.