Division of Quantitative Methods and Modeling, Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, Maryland, USA.
Clinical Pharmacology, AbbVie, North Chicago, Illinois, 60064, USA.
AAPS J. 2023 Oct 2;25(6):96. doi: 10.1208/s12248-023-00862-x.
The number of modeling and simulation applications, including physiologically based pharmacokinetic (PBPK) models, physiologically based biopharmaceutics modeling (PBBM), and empirical models, has been constantly increasing along with the regulatory acceptance of these methodologies. While aiming at minimizing unnecessary human testing, these methodologies are used today to support the development and approval of novel drug products and generics. Modeling approaches are leveraged today for assessing drug-drug interaction, informing dose adjustments in renally or hepatically impaired patients, perform dose selection in pediatrics and pregnant women and diseased populations, and conduct biopharmaceutics-related assessments such as establish clinically relevant specifications for drug products and achieve quality assurance throughout the product life cycle. In the generics space, PBPK analyses are utilized toward virtual bioequivalence assessments within the scope of alternative bioequivalence approaches, product-specific guidance development, and food effect assessments among others. Case studies highlighting the evolving and expanding role of modeling and simulation approaches within the biopharmaceutics space were presented at the symposium titled "Model Informed Drug Development (MIDD): Role in Dose Selection, Vulnerable Populations, and Biowaivers - Chemical Entities" and Prologue "PBPK/PBBM to inform the Bioequivalence Safe Space, Food Effects, and pH-mediated DDIs" at the American Association of Pharmaceutical Scientists (AAPS) PharmSci 360 Annual Meeting in Boston, MA, on October 16-19, 2022, and are summarized here.
随着这些方法学的监管接受度不断提高,建模和模拟应用的数量一直在不断增加,包括基于生理学的药代动力学 (PBPK) 模型、基于生理学的生物药剂学建模 (PBBM) 和经验模型。虽然这些方法学的目的是尽量减少不必要的人体测试,但今天它们被用于支持新型药物产品和仿制药的开发和批准。今天,建模方法被用于评估药物相互作用,为肾功能或肝功能受损患者调整剂量,在儿科和孕妇以及患病人群中进行剂量选择,并进行与生物药剂学相关的评估,例如为药物产品建立临床相关的规格,并在整个产品生命周期内实现质量保证。在仿制药领域,PBPK 分析用于替代生物等效性方法范围内的虚拟生物等效性评估、产品特定指导原则的制定以及食物影响评估等。在 2022 年 10 月 16 日至 19 日于马萨诸塞州波士顿举行的美国药物科学家协会 (AAPS) PharmSci 360 年会上,题为“模型指导药物开发 (MIDD):在剂量选择、脆弱人群和生物豁免方面的作用 - 化学实体”和序幕“PBPK/PBBM 告知生物等效安全范围、食物影响和 pH 介导的 DDI”的专题讨论会上展示了突出建模和模拟方法在生物药剂学领域中不断发展和扩大作用的案例研究,现总结如下。