重组表达生物制品生产中病毒清除验证策略研究进展

Research progress in viral clearance validation strategy of recombinant biological products

采用真核表达系统生产的重组生物制品,由于其生产基质的特殊性而具有潜在的病毒污染风险,且风险引入方式多样。当前,世界各主要监管机构均发布了关于此类产品生产过程中病毒安全保障的指导原则,其中由人用药品注册技术要求国际协调会议(ICH)发布的Q5A(R1)适用国家广泛、认可度较高。本文将从指导原则的适用范围、新型检测和分析手段、现行工艺验证方法发展、新增工艺验证途径、先进制造技术条件下的工艺验证和风险消除策略5个方面,对目前重组表达生物制品生产中病毒清除工艺的研究方向进行讨论,旨在探索技术要求的科学性,引起业界和监管机构的共同思考。

Because of the particularity of the production cell substrates,the potential risk of virus contamination in recombinant biological products produced by eukaryotic expression system could be introduced in various ways.Major regulatory agencies in the world-wide have issued guidelines about the viral safety in the production of such products,among which Q5 A(R1),issued by the International Council for Harmonization(ICH),is widely accepted and highly recognized by different countries.In order to explore the scientific nature of the technical requirements and arouse the common thinking of the industry and regulatory authorities,this article discussed the current research progress in virus removal and inactivation process in the production of recombinant biological products from five aspects,which are the applicable scope of the guideline,new virus assays and analytical methods,the progress of validation approaches,new validation method that have emerged or evolved,and virus clearance validation and risk mitigation strategies for advanced manufacturing.