重组蛋白生物制品灌流培养工艺及药学评价考量

Considerations on pharmaceutical evaluation of perfusion fermentation of recombinant protein biological products

灌流培养作为一种连续细胞培养技术,较传统批量生产工艺有利于企业生产成本控制,并可根据供应需求灵活调整规模。本文对比了传统批量发酵工艺与灌流工艺,明确了灌流培养工艺特点。结合国际人用药品注册技术协会目前正在起草的指导原则,本文从细胞传代稳定性研究、批次及规模定义、生产工艺控制、外源因子控制、生产工艺验证等方面,总结了灌流培养工艺药学评价的考量内容。

As a continuous cell culture technology,perfusion fermentation is more beneficial to cost control than traditional batch fermentation and can be flexibly arranged according to the supply change.In this paper,the characteristics and advantages of perfusion fermentation are clarified by comparing the batch fermentation with perfusion fermentation.In combination with the guidelines currently being drafted by the International Council on Harmonization,the considerations for pharmaceutical evaluation of cell passage stability study,batch and scale definition,process control,viral safety,and process verification of perfusion fermentation are summarized in this paper.