Emerging Role of Organ‐on‐a‐Chip Technologies in Quantitative Clinical Pharmacology Evaluation

Abstract

The recently enacted Prescription Drug User Fee Act ( PDUFA ) VI includes in its performance goals “enhancing regulatory science and expediting drug development.” The key elements in “enhancing regulatory decision tools to support drug development and review” include “advancing model‐informed drug development ( MIDD ).” This paper describes (i) the US Food and Drug Administration ( FDA ) Office of Clinical Pharmacology's continuing efforts in developing quantitative clinical pharmacology models (disease, drug, and clinical trial models) to advance MIDD , (ii) how emerging novel tools, such as organ‐on‐a‐chip technologies or microphysiological systems, can provide new insights into physiology and disease mechanisms, biomarker identification and evaluation, and elucidation of mechanisms of adverse drug reactions, and (iii) how the single organ or linked organ microphysiological systems can provide critical system parameters for improved physiologically‐based pharmacokinetic and pharmacodynamic evaluations. Continuous public‐private partnerships are critical to advance this field and in the application of these new technologies in drug development and regulatory review.

Technology development of breathing thermal manikin and its application and prospect in healthy building

“…除动物模型之外, Dilger等人 [90] 、Kasurinen等人 [91] 和Marchetti等人 [92] 使用体外细胞培养法, 通过对人体 [93] . 由于当前体外细胞培养模型的局限 性, Huh等人 [94] 基于微流控技术的细胞装置, 建立体外 肺芯片, 将多个器官组织信息集成在一个单独的芯片 上, 形成"器官-芯片"系统 [95] , 更好地模拟和控制生理 微环境, 可以较快地观察到肺部疾病患者在相关暴露 环境下引起的分子、细胞和组织水平的特异性反应, 对靶向治疗和生物标记物研究具有重要意义 [96] . The core concept of healthy building is "people-oriented".…”

Applications of the microphysiology systems database for experimental ADME-Tox and disease models

“…1,2 A number of recent reviews describe in detail an expanding number of MPS models of human organs being developed. [3][4][5][6][7] The goal of all of the MPS models in development or in use has been to produce biologically relevant experimental models that replicate key aspects of normal or diseased human physiology. When these experimental models closely simulate the clinical physiology, they can provide valuable information for computational modeling allowing for a better understanding of normal physiology, as well as the pathophysiology of the disease.…”

“…Further, the physiologically relevant models can play a role in better understanding the pharmacology, and absorption, distribution, metabolism, excretion, and toxicology (ADME-Tox) properties of existing and new drug candidates. 5 With the use of patient specific induced pluripotent stem cells (iPSC), models can be developed to enable patient heterogeneity to be engineered to guide clinical trial design and personalized medicine.…”

Applications of the Microphysiology Systems Database for Experimental ADME-Tox and Disease Models

“…1, 2 A number of recent reviews describe in detail an expanding number of MPS models of human organs being developed. [3][4][5][6][7] The goal of all of the MPS models in development or in use has been to produce biologically relevant experimental models that replicate key aspects of normal or diseased human physiology. When these experimental models closely simulate the clinical physiology, they can provide valuable information for computational modeling allowing for a better understanding of normal physiology, as well as the pathophysiology of the disease.…”