Role of Modeling and Simulation in the Development of Novel and Biosimilar Therapeutic Proteins.

Modeling and simulation (M&S) is an important enabler of knowledge integration in novel biological product development programs. Given the volume of data generated from clinical trials and the complexity of pharmacokinetic (PK) and pharmacodynamic (PD) properties for reference products, extending the use of M&S to biosimilar development is logical. Assessing PK and PD similarity is normally a critical part of demonstrating biosimilarity to a reference product. Thoughtful considerations are necessary in study design to minimize the PK and PD variability, thereby increasing the sensitivity for detecting potential differences between products. In addition, the sensitivity of PD biomarkers depends partly on their relevance to the mechanism(s) of action and the dynamic range of PD response(s), including the impact of certain structural differences on PD in the relevant population. As such, opportunities exist for leveraging the available M&S knowledgebase to maximize the efficiency in the design and interpretation of PK and PD similarity studies. This article describes M&S applications which have contributed to and can continue to enhance biosimilar development programs. Published by Elsevier Inc.