German Centre for the Protection of Laboratory Animals (Bf3R), German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
Section on Pharmacology, Toxicology and Kinetics, Medicines Evaluation Board, Utrecht, The Netherlands.
Crit Rev Toxicol. 2021 Jul;51(6):540-554. doi: 10.1080/10408444.2021.1953439. Epub 2021 Aug 31.
Organ-on-chip (OoC) systems are microfabricated cell culture devices designed to model functional units of human organs by harboring an generated organ surrogate. In the present study, we reviewed issues and opportunities related to the application of OoC in the safety and efficacy assessment of chemicals and pharmaceuticals, as well as the steps needed to achieve this goal. The relative complexity of OoC over simple assays provides advantages and disadvantages in the context of compound testing. The broader biological domain of OoC potentially enhances their predictive value, whereas their complexity present issues with throughput, standardization and transferability. Using OoCs for regulatory purposes requires detailed and standardized protocols, providing reproducible results in an interlaboratory setting. The extent to which interlaboratory standardization of OoC is feasible and necessary for regulatory application is a matter of debate. The focus of applying OoCs in safety assessment is currently directed to characterization (the biology represented in the test) and qualification (the performance of the test). To this aim, OoCs are evaluated on a limited scale, especially in the pharmaceutical industry, with restricted sets of reference substances. Given the low throughput of OoC, it is questionable whether formal validation, in which many reference substances are extensively tested in different laboratories, is feasible for OoCs. Rather, initiatives such as open technology platforms, and collaboration between OoC developers and risk assessors may prove an expedient strategy to build confidence in OoCs for application in safety and efficacy assessment.
器官芯片 (OoC) 系统是微加工细胞培养设备，旨在通过容纳生成的器官替代物来模拟人体器官的功能单元。在本研究中，我们综述了 OoC 在化学品和药物的安全性和功效评估中的应用相关的问题和机遇，以及实现这一目标所需的步骤。与简单的 测定相比，OoC 的相对复杂性在化合物测试方面具有优势和劣势。OoC 更广泛的生物学领域可能会提高其预测价值，而其复杂性则存在通量、标准化和可转移性方面的问题。将 OoC 用于监管目的需要详细和标准化的方案，以便在实验室间提供可重复的结果。在多大程度上可以实现 OoC 的实验室间标准化以及是否有必要将其用于监管应用是一个有争议的问题。将 OoC 应用于安全性评估的重点目前是对其进行特征描述（测试中所代表的生物学）和资格鉴定（测试的性能）。为此，尤其是在制药行业中，对 OoC 的评估规模有限，并且参考物质的选择范围有限。考虑到 OoC 的通量较低，正式验证（在许多实验室中对许多参考物质进行广泛测试）对于 OoC 是否可行是值得怀疑的。相反，开放技术平台等举措以及 OoC 开发人员和风险评估人员之间的合作可能是建立对 OoC 在安全性和功效评估中应用的信心的一种便捷策略。
