临床期间生物制品药学变更的非临床评价策略和案例分析

Nonclinical Evaluation Strategies and Case Analyses for Chemistry, Manufacturing, and Controls (CMC) Changes in Biological Products during Clinical Development

关键词:  临床期间  生物制品药学变更  非临床评价

Key words:  During clinical development  CMC changes  Nonclinical evaluation

摘要:

生物制品临床试验期间药学开发是持续性过程,期间发生药学变更不可避免。药学变更可能会导致产品质量属性的改变,进而影响到产品的安全性和/或有效性,需要开展变更前后样品的可比性研究,以桥接已有的非临床和/或临床研究数据,这种情况下,可能需要开展必要的非临床桥接研究。本文结合已发布的技术文件和具体案例,阐述临床试验期间生物制品药学变更非临床评价的基本思路和关注点,以期为该类变更的顺利进行提供参考。

Abstract:

Pharmaceutical development of biological products during clinical trials is an continuous process in which manufacturing changes are inevitable. Pharmaceutical changes may lead to changes in critical quality attributes, potentially impacting product safety and/or efficacy. Assessing the comparability of biological products before and after changes is therefore required to bridge existing nonclinical and/or clinical data. In some cases, dedicated nonclinical bridging studies are warranted. Integrating published technical paper with specific cases analyses, this paper delineates the fundamental rationale and pivotal considerations for the nonclinical assessment of CMC changes of biological products during clinical development, in order to provide reference for facilitating the efficient advancement of such changes.