Pharmaceutical Sciences, Merck, 770 Sumneytown Pike, West Point, Pennsylvania, 19486, USA.
Novartis Institutes for Biomedical Research, One Health Plaza, East Hanover, New Jersey, 07936, USA.
AAPS J. 2018 Apr 9;20(3):60. doi: 10.1208/s12248-018-0213-x.
On May 15th-17th, 2017, the US FDA and the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) held a workshop at the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI), to discuss the role of dissolution testing and translational modeling and simulation in enabling patient-centric solid oral drug product development. This 3-day event was attended by scientists from regulatory agencies, pharmaceutical companies, and academia. The workshop included podium presentations followed by breakout session discussions. The first day of the meeting focused on the challenges in dissolution method development and the role of dissolution testing throughout drug product development. On the second day, approaches to establish a link between in vitro testing and in vivo drug product performance (e.g., systemic exposure) were presented. Overall success rates and challenges in establishing IVIVCs via traditional and modern physiologically based pharmacokinetic (PBPK) modeling and simulation approaches were discussed. Day 3 provided an opportunity to discuss the expectations for establishing clinically relevant drug product specifications (CRDPS). It was recognized that understanding the impact of formulation and process variations on dissolution and in vivo performance is critical for most drug products formulated with poorly soluble drugs to ensure consistent product performance. The breakout sessions served as platforms for discussing controversial topics such as the clarification of dissolution terminology, PBPK model development and validation expectations, and approaches to set CRDPS. The meeting concluded with a commitment to continue the dialog between regulators, industry, and academia to advance overall product quality understanding.
2017 年 5 月 15 日至 17 日，美国 FDA 和国际药品创新与质量联盟（IQ）在马里兰大学卓越监管科学与创新中心（M-CERSI）举行了一场研讨会，讨论了在以患者为中心的固体口服药物产品开发中，溶出度测试和转化模型模拟所起的作用。来自监管机构、制药公司和学术界的科学家参加了为期三天的活动。该研讨会包括主题演讲和分组讨论。会议第一天的重点是溶出度方法开发的挑战，以及溶出度测试在药物产品开发中的作用。第二天，介绍了建立体外测试与体内药物产品性能（如全身暴露）之间联系的方法。讨论了通过传统和现代基于生理的药代动力学（PBPK）建模和模拟方法建立 IVIVC 的总体成功率和挑战。第三天提供了一个机会来讨论建立临床相关药物产品规格（CRDPS）的期望。人们认识到，对于大多数用难溶性药物配制的药物产品，了解配方和工艺变化对溶出度和体内性能的影响至关重要，以确保产品性能的一致性。分组讨论为讨论有争议的话题提供了平台，如澄清溶出度术语、PBPK 模型开发和验证期望，以及建立 CRDPS 的方法。会议最后承诺继续监管机构、行业和学术界之间的对话，以提高对整体产品质量的认识。
