Drug Metabolism and Pharmacokinetics, Theravance Biopharma US, Inc, South San Francisco, CA, USA.
Lab Chip. 2019 Sep 27;19(19):3152-3161. doi: 10.1039/c9lc00492k.
The lung is a complex organ; it is both the initial barrier for inhaled agents and the site of metabolism and therapeutic effect for a subset of systemically administered drugs. Comprised of more than 40 cell types that are responsible for various important functions, the lung's complexity contributes to the subsequent challenges in developing complex in vitro co-culture models (also called microphysiological systems (MPS), complex in vitro models or organs-on-a-chip). Although there are multiple considerations and limitations in the development and qualification of such in vitro systems, MPS exhibit great promise in the fields of pharmacology and toxicology. Successful development and implementation of MPS models may enable mechanistic bridging between non-clinical species and humans, and increase clinical relevance of safety endpoints, while decreasing overall animal use. This article summarizes, from a biopharmaceutical industry perspective, essential elements for the development and qualification of lung MPS models. Its purpose is to guide MPS developers and manufacturers to expedite MPS utilization for safety assessment in the biopharmaceutical industry.
肺是一个复杂的器官；它既是吸入剂的初始屏障，也是一部分全身给予药物的代谢和治疗效果的部位。由 40 多种负责各种重要功能的细胞类型组成，肺的复杂性导致在开发复杂的体外共培养模型（也称为微生理系统（MPS）、复杂的体外模型或芯片上器官）方面存在后续挑战。尽管在开发和鉴定此类体外系统时有多种考虑因素和限制，但 MPS 在药理学和毒理学领域具有广阔的应用前景。成功开发和实施 MPS 模型可能会使非临床物种和人类之间的机制桥接成为可能，并提高安全性终点的临床相关性，同时减少整体动物使用。本文从生物制药行业的角度总结了肺 MPS 模型的开发和鉴定的基本要素。其目的是指导 MPS 开发人员和制造商加快 MPS 在生物制药行业安全性评估中的利用。
