ABSTRACT
This chapter outlines some critical issues that are commonly encountered when conducting a pharmacokinetic and pharmacodynamic (PK/PD) bridging study with multiple reference products. When an innovative biological drug (reference) product is going off patent protection, biosimilar companies or sponsors may seek regulatory approval for similar biological biosimilar (test) products to the reference product. The stepwise approach starts with analytical studies for functional and structural characterization of critical quality attributes (CQAs) at various stages of the manufacturing process followed by animal studies for the assessment of toxicity, clinical pharmacology for (PK/PD) studies, and clinical studies for the assessment of immunogenicity, safety/tolerability, and efficacy. For assessing biosimilar products, however, there may be multiple references, e.g., a European Union (EU)-approved reference product and a US-licensed reference product of the same innovative product.
