Beilmann Mario, Adkins Karissa, Boonen Harrie C M, Hewitt Philip, Hu Wenyue, Mader Robert, Moore Susanne, Rana Payal, Steger-Hartmann Thomas, Villenave Remi, van Vleet Terry
Global Nonclinical Safety & DMPK, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
Sanofi US, Cambridge, MA, USA.
Nat Rev Drug Discov. 2025 May 2. doi: 10.1038/s41573-025-01182-9.
The development of new approach methodologies (NAMs) and advances with in vitro testing systems have prompted revisions in regulatory guidelines and inspired dedicated in vitro/ex vivo studies for nonclinical safety assessment. This Review by a safety reflection initiative subgroup of the European Federation of Pharmaceutical Industries and Associations (EFPIA)/Preclinical Development Expert Group (PDEG) summarizes the current state and potential application of in vitro studies using human-derived material for safety assessment in drug development. It focuses on case studies from recent projects in which animal models alone proved to be limited or inadequate for safety testing. It further highlights four categories of drug candidates for which alternative in vitro approaches are applicable and discusses progress in using in vitro testing solutions for safety assessment in these categories. Finally, the article highlights new risk assessment strategies, initiatives and consortia promoting the advancement of NAMs. This collective work is meant to encourage the use of NAMs for more human-relevant safety assessment, which should ultimately result in reduced animal testing for drug development.
新方法学（NAMs）的发展以及体外测试系统的进步促使监管指南进行修订，并激发了用于非临床安全性评估的专门体外/离体研究。欧洲制药工业协会联合会（EFPIA）/临床前开发专家组（PDEG）的一个安全反思倡议小组撰写的这篇综述总结了使用人源材料进行体外研究在药物开发安全性评估中的现状和潜在应用。它重点关注近期项目中的案例研究，在这些项目中，仅动物模型在安全性测试方面被证明存在局限性或不充分。它进一步强调了适用于替代体外方法的四类候选药物，并讨论了在这些类别中使用体外测试解决方案进行安全性评估的进展。最后，本文强调了促进NAMs发展的新风险评估策略、倡议和联盟。这项集体工作旨在鼓励使用NAMs进行更具人体相关性的安全性评估，这最终应能减少药物开发中的动物试验。
