关于生物制品工艺验证的审评实践与思考

Discussion on general principle and key points of process validation for biologics

有效的工艺验证是药品质量的重要保证。由于生物制品来源于细胞基质、制备工艺复杂,具备结构表征不完全等特点,生物制品的工艺验证需进行特殊考虑。本文根据国内外相关指导原则并结合药品审评工作实践,总结了生物制品工艺验证中关于细胞基质、发酵与纯化过程、病毒安全性、层析介质寿命与一次性反应器耗材,以及中间体稳定性等的一般要求。同时,就目前国内生物制品注册管理中出现的工艺验证相关共性问题进行探讨。

Effective process validation contributes significantly to assure the drug quality. Due to derivation from cell substrate, complexity of manufacturing process and not-well characterization of molecular structure, some specific points should be taken into account in the process validation of biologics. In this review, the general issues related to biologics process validation were summarized, including cell substrate, fermentation and purification processes, viral safety, life of chromatographic medium and disposable supplies, as well as stability of intermediate. Moreover, some common problems related to regulatory submission of process validation data were also discussed.