Pharmaceutical Research & Development, Formulation & Process Sciences, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
AstraZeneca, Pharmaceutical Technology & Development, Silk Road Business Park, Charter Way, Macclesfield, SK10 2NA, UK.
AAPS J. 2019 Jan 23;21(2):19. doi: 10.1208/s12248-019-0292-3.
The establishment of an in vitro-in vivo correlation (IVIVC) is considered the gold standard to establish in vivo relevance of a dissolution method and to utilize dissolution data in the context of regulatory bioequivalence questions, including the development of dissolution specifications. However, several recent publications, including industry surveys and reviews from regulatory agencies, have indicated a low success rate for IVIVCs, especially for immediate-release formulations. In recent years, the use of physiologically based pharmacokinetics (PBPK) and absorption modeling, as a tool to facilitate formulation development, has been attracting increased attention. This manuscript provides an industry perspective on the current challenges with establishing IVIVCs and the potential PBPK and absorption modeling offer to increase their impact. Case studies across both immediate-release and extended-release formulations from five pharmaceutical companies are utilized to demonstrate how physiologically based IVIVC (PB-IVIVC) may facilitate drug product understanding and to inform bioequivalence assessment and clinically relevant specifications. Finally, PB-IVIVC best practices and a strategy for model development and application are proposed.
建立体外-体内相关性(IVIVC)被认为是建立溶解方法体内相关性的金标准,并利用溶解数据来解决监管生物等效性问题,包括制定溶解标准。然而,最近的几份出版物,包括来自监管机构的行业调查和综述,表明 IVIVC 的成功率较低,特别是对于速释制剂。近年来,生理药代动力学(PBPK)和吸收建模的应用作为一种促进制剂开发的工具,引起了越来越多的关注。本文从行业角度探讨了目前建立 IVIVC 面临的挑战,以及 PBPK 和吸收建模可能增加其影响的潜力。本文利用来自五家制药公司的速释和缓控释制剂的案例研究,展示了生理基础 IVIVC(PB-IVIVC)如何促进药物产品的理解,并为生物等效性评估和临床相关规格提供信息。最后,提出了 PB-IVIVC 的最佳实践以及模型开发和应用的策略。