The liver is critical to consider during drug development because of its central role in the handling of xenobiotics, a process which often leads to localized and/or downstream tissue injury. Our ability to predict human clinical safety outcomes with animal testing is limited due to species differences in drug metabolism and disposition, while traditional human in vitro liver models often lack the necessary in vivo physiological fidelity. To address this, increasing numbers of liver microphysiological systems (MPS) are being developed, however the inconsistency in their optimization and characterization often leads to models that do not possess critical levels of baseline performance that is required for many pharmaceutical industry applications. Herein we provide a guidance on best approaches to benchmark liver MPS based on 3 stages of characterization that includes key performance metrics and a 20 compound safety test set. Additionally, we give an overview of frequently used liver injury safety assays, describe the ideal MPS model, and provide a perspective on currently best suited MPS contexts of use. This pharmaceutical industry guidance has been written to help MPS developers and end users identify what could be the most valuable models for safety risk assessment.

中文翻译：

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制药行业中用于安全风险评估的肝微生理系统开发指南。

在药物开发过程中，考虑到肝脏至关重要，因为肝脏在处理异种生物中起着重要作用，该过程通常会导致局部和/或下游组织损伤。由于药物代谢和处置的物种差异，我们通过动物试验预测人类临床安全结果的能力受到限制，而传统的人类体外肝模型通常缺乏体内必需的生理保真度。为了解决这个问题，正在开发越来越多的肝脏微生理系统（MPS），但是它们的优化和表征不一致会导致模型不具备许多制药行业应用所需的关键基线性能水平。在此，我们基于3个阶段的表征（包括关键性能指标和20种化合物安全性测试集），为基准肝MPS的最佳方法提供指导。此外，我们概述了常用的肝损伤安全性检测方法，描述了理想的MPS模型，并就当前最适合的MPS使用环境提供了一个观点。