Analysis of the Key Issues in Comparative PhaseⅢClinical Study of Biosimilars

The market approval of most biosimilars still requires one/multiple comparative phase Ⅲ clinical studies, because small differences in the complex structure of biologics may lead to changes in clinical efficacy and immunogenicity. Unlike the approval of innovative drugs, the key points of phase Ⅲ clinical comparative study are the selection of indications, the selection of clinical endpoints and study period, and the determination of equivalence margin, etc. In addition, in the clinical review and approval of biosimilars, there are some cases of appropriate relaxation of standards after scientific consideration of the results. For some biosimilars, comparative clinical studies were waived with pivotal evidence for similarity from pharmacokinetics/pharmacodynamics(PK/PD) comparison, which is an important trend for the development of regulatory science. This paper reviews the issues regarding comparative clinical studies for the development of biosimilars, aiming to provide some reference for the comparative clinical study of more complex biosimilars in China.