本文分享了8月29日的诉讼程序,2023年(第1天)研讨会“基于生理的生物制药建模(PBBM)药物产品质量最佳实践:监管和行业观点”。当天的焦点是模型参数化;来自加拿大的监管机构,美国,瑞典,比利时,挪威介绍了他们对IQ联盟行业成员提交的PBBM案例研究的看法。演讲分享了监管机构在模拟演习中提出的关键问题,关于PBBM输入参数及其理由。这些演讲还阐明了监管评估过程,内容,以及未来PBBM监管提交的格式要求。此外,第1天的分组演讲和讨论为科学家在参数化PBBM时面临的关键问题提供了分享最佳实践的机会。关键问题包括结晶药物与无定形药物的药物溶解度的测量和整合;赋形剂对表观药物溶解度/过饱和的影响;溶解药物表面酸碱反应的建模;根据配方和药物特性选择溶出方法,以预测从体内PBM的各种药物吸收特性和体内药物的不同机制模型,预测体内药物渗透的不同
This Article shares the proceedings from the August 29th, 2023 (day 1) workshop \"Physiologically Based
Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives\". The focus of the day was on model parametrization; regulatory authorities from Canada, the USA, Sweden, Belgium, and Norway presented their views on PBBM case studies submitted by industry members of the IQ consortium. The presentations shared key questions raised by regulators during the mock exercise, regarding the PBBM input parameters and their justification. These presentations also shed light on the regulatory assessment processes, content, and format requirements for future PBBM regulatory submissions. In addition, the day 1 breakout presentations and discussions gave the opportunity to share best practices around key questions faced by scientists when parametrizing PBBMs. Key questions included measurement and integration of drug substance solubility for crystalline vs amorphous drugs; impact of excipients on apparent drug solubility/supersaturation; modeling of acid-base reactions at the surface of the dissolving drug; choice of dissolution methods according to the formulation and drug properties with a view to predict the in vivo performance; mechanistic modeling of in vitro product dissolution data to predict in vivo dissolution for various patient populations/species; best practices for characterization of drug precipitation from simple or complex formulations and integration of the data in PBBM; incorporation of drug permeability into PBBM for various routes of uptake and prediction of permeability along the GI tract.