Statistical methods for assessing interchangeability of biosimilars.

Unlike traditional small molecule (chemical) drug products, the development of biologic products is very different and variable with respect to the manufacturing process and environmental factors such as light and temperature. The complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and possibility of severe immunogenicity reactions make quantitative evaluation of follow-on biologics a great challenge to both scientific community and regulatory agencies. In this article, we propose a general approach for development of a biosimilarity index based on the concept of reproducibility probability for quantitative evaluation of biosimilarity and interchangeability. The proposed method is robust regardless the biosimilarity criteria used and/or study design employed.