Office of Clinical Pharmacology (OCP), Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA.
Clin Transl Sci. 2019 Mar;12(2):113-121. doi: 10.1111/cts.12627.
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.
最近颁布的《处方药使用者付费法案》（PDUFA）第六部分将“增强监管科学并加快药物开发”纳入其绩效目标。“增强监管决策工具以支持药物开发和审查”的关键要素包括“推进基于模型的药物开发（MIDD）”。本文描述了（i）美国食品和药物管理局（FDA）临床药理学办公室为推进 MIDD 而持续努力开发定量临床药理学模型（疾病、药物和临床试验模型），（ii）新兴的新型工具，如器官芯片技术或微生理系统，如何为生理学和疾病机制、生物标志物的识别和评估以及药物不良反应机制的阐明提供新的见解，以及（iii）单个器官或连接的器官微生理系统如何为改进基于生理学的药代动力学和药效学评估提供关键系统参数。持续的公私合作伙伴关系对于推进这一领域以及在药物开发和监管审查中应用这些新技术至关重要。
