ABSTRACT
This chapter discusses some insights and clarification between the use of 90% confidence interval for assessment generic/biosimilar drugs and the use of 95% confidence interval approach for assessment of new drugs. It provides interpretation of totality-of-the-evidence from academic and/or pharmaceutical perspectives. The chapter provides the inconsistencies of test results for critical quality attributes (CQAs) from Tier 1 and other Tiers. It also discusses the potential use of individual bioequivalence for biosimilarity assessment in biosimilar studies. The chapter deals with some commonly asked questions during the implementation of analytical similarity assessment. A frequently asked question is "What is the difference between in vitro bioequivalence testing for generic drug products and equivalence testing for analytical similarity in CQAs in biosimilar studies?" Food and Drug Administration's recommended stepwise approach focuses on three major domains, namely, analytical, pharmacokinetics/pharmacodynamics, and clinical similarity, which are highly correlated under models. The chapter outlines several practical issues that are commonly encountered during the implementation of the stepwise approach.
