Rahman Shekh M, Krishna Ashok, Sullenberger Catherine, Jeong Ye Eun, Garcia M Iveth, Bhardwaj Bhavya, Geiger Robert M, Blinova Ksenia, Ford Kevin A
Division of Applied Regulatory Science (DARS), Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA), Silver Spring, MD, USA.
ALTEX. 2025;42(2):224-256. doi: 10.14573/altex.2409221. Epub 2024 Dec 20.
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.
微生理系统（MPS）是复杂的体外工具，它整合了源自各种健康或疾病状态的人类或动物组织及器官的细胞。虽然MPS存在局限性，包括缺乏全球统一的标准化指南，但它们在药物开发的某些领域已被证明具有影响力。对MPS的进一步研究和监管认可将有助于使其在未来成为更有效的工具。本综述探讨了人肝脏、肠道、肺和心脏MPS在药物开发中的潜在应用，重点关注疾病建模、安全性评估和药代动力学研究。讨论了系统评估的各种技术参数和相关终点，以及细胞来源、可重复性和多个组织或器官整合等挑战。强调了学术界、产业界和监管机构之间合作制定标准化方案和验证标准的重要性。随着不断进步和合作倡议，MPS有望在提高非临床测试的预测性和可靠性方面发挥重要作用，从而改变药物开发和监管流程。
