DESIGN OF BIOLOGICAL EQUIVALENCE PROGRAMS FOR THERAPEUTIC BIOTECHNOLOGY PRODUCTS IN CLINICAL DEVELOPMENT - A PERSPECTIVE

The determination of biological equivalence requires that studies are conducted to establish that two molecules, two formulations, or two do sing regimens, for example, are indistinguishable with respect to safe ty and efficacy profiles that have been previously established. The cr iteria that are used to establish biological equivalence will depend o n the nature of the change (e.g., molecular, process, formulation), th e stage of the development program, the duration of treatment, and the intended clinical indications. Key components of an equivalence progr am include chemical characterization, in vitro and in vivo bioactivity against reference material, pharmacokinetics, and safety. Special con siderations for patient populations, endogenous concentrations, enviro nmental factors, immunogenicity, assay methodology, biochemical identi ty, pharmacodynamic equivalence, and statistical methodology are discu ssed. in addition, the role of preclinical in vivo assessments is addr essed. Specific case studies provide insight into the varied nature of approaches that are currently employed.