【摘要】 近年来,生物技术药物特别是单抗类生物药逐渐成为新药的研发主体。但蛋白质类生物药普遍存在结构复杂且不稳定的问题,尤其在生产过程中会经历多种不稳定性因素,造成生物药的降解和失活。生物药的制备工艺非常复杂,往往经历生物合成(如微生物发酵/细胞培养)、原液纯化和精制(如色谱纯化、除病毒)和制剂工艺(如制剂配置、无菌过滤、灌装、冻干和灯检)等各个生产以及储存、运输等环节。因此解决这些不稳定性问题是生物药最终成功应用于临床的关键。本文对生物药生产过程中的降解途径进行归纳,并提出相应的解决方案。更多还原

【Abstract】 Recently,biotherapeutics,especially monoclonal antibody-based biotherapeutics,have become increasingly important as novel therapeutic products. However,biotherapeutics are usually not only complex in structure,but also unstable,especially during the manufacturing bioprocesses,leading to their degradation and inactivation. The manufacturing prccesses are substantially complex,and generally include drug substance biosynthesis(i.e. fermentation or cell culture),purification and refinement(i.e. chromatography and viral clearance),and drug product formulation and fill-finish(i.e. compounding,sterilization,filling,freeze-drying and inspection). Therefore,it is of vital importance for biotherapeutics to remain stable during manufacturing processes. This review summarizes major factors that affect the degradation of biotherapeutics during manufacturing processes and proposes corresponding solutions in each step of the manufacturing process.更多还原