Opportunities and challenges for human microphysiological systems in drug development

Abstract

Microphysiological systems (MPS) are complex in vitro tools that incorporate cells derived from various healthy or disease-state human or animal tissues and organs. While MPS have limitations, including a lack of globally harmonized guidelines for standardization, they have already proven impactful in certain areas of drug development. Further research and regulatory acceptance of MPS will contribute to making them even more effective tools in the future. This review explores the potential applications of human liver, gut, lung, and cardiac MPS in drug development, focusing on disease modeling, safety assessment, and pharmacokinetic studies. Various technical param­eters and relevant endpoints for system assessment are discussed alongside challenges such as cell sourcing, reproducibility, and the integration of multiple tissues or organs. The importance of col­laborative efforts between academia, industry, and regulatory agencies to develop standardized protocols and validation criteria is emphasized. With ongoing advancements and cooperative ini­tiatives, MPS are poised to play a significant role in enhancing the predictivity and reliability of nonclinical testing, thereby transforming drug development and regulatory processes.

Keywords: complex in vitro models; drug development; microphysiological systems; regulatory applications; safety assessment.