European Medicines Agency (EMA), London, UK.
Medicines and Healthcare products Regulatory Agency (MHRA), London, UK.
Clin Pharmacol Ther. 2017 Jul;102(1):98-105. doi: 10.1002/cpt.539. Epub 2016 Dec 26.
Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision-making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA.
生理药代动力学（PBPK）模型是药物开发和监管评估中的一种有价值的工具，因为它提供了在各种人群和情况下用机制理解模拟化合物药代动力学的机会。这项工作回顾了在 2015 年底前向欧洲药品管理局（EMA）提交的选定监管程序中此类模型的使用和影响，以及随后在与评估这些程序相关的公开文件中的反映。显然，监管公开文件中对 PBPK 模型的引用低估了其使用。显示了提交的 PBPK 模型数量随时间的积极趋势，在许多情况下，这些模型的结果可能会影响决策过程或导致产品标签中的建议。这些结果证实了在这一领域需要监管指导，EMA 目前正在制定这一指导。
