3Rs质控方法在WHO生物制品指导原则中的实施进展和挑战  

Progress and challenges in the implementation of 3Rs quality control approaches in WHO guidelines on biologicals

作　　者：贺庆[1] 谭德讲[1] 马霄[1] 郑逸阳 刘思含 张羽 王军志[1] HE Qing;TAN De-jiang;MA Xiao;ZHENG Yi-yang;LIU Si-han;ZHANG Yu;WANG Jun-zhi(National Institutes for Food and Drug Control,Beijing 102629,China;Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]沈阳药科大学,沈阳110016

出　　处：《中国新药杂志》2024年第16期1659-1664,共6页Chinese Journal of New Drugs

基　　金：中国食品药品检定研究院关键技术研究基金资助项目:肿瘤新生抗原mRNA治疗性癌症疫苗的非临床药效评价关键技术研究(GJJS-2022-6-2)。

摘　　要：世界卫生组织(WHO)生物制品和疫苗指导原则目前在五大质控领域(内毒素/热原、神经毒性、外源性因子、效价和免疫原性、特异性毒性)全面整合并实施以替代、优化和减少(replacement,refinement and reduction,3Rs)实验动物使用的3Rs质控方法。目前3Rs质控方法在内毒素/热原领域已取得较大进展,全球药品监管机构和制药企业均在开发应用内毒素/热原的非动物检测技术[如单核细胞活化法(monocyte activation test,MAT)、重组C因子细菌内毒素检测法(recombinant factor C bacterial endotoxin test,rFC BET)],且在其他领域也均取得一定进展。3Rs质控方法的进一步发展正面临某些共同挑战,如缺少国际统一的监管、标准及技术验证指导原则、如何科学评价不同检测技术间的可比性和相关性、如何全球推广和普及先进检测技术等问题。WHO guidelines on biologicals and vaccines are fully integrating and implementing the 3Rs quality control approaches to replace,optimize and reduce the use of animals in five quality control fields including endotoxin/pyrogen,neurovirulence,adventitious agents,potency and immunogenicity,specific toxicity.At present,3Rs quality control approaches have made great progress in the field of endotoxin/pyrogen,and global regulators and pharmaceutical companies are developing and applying non-animal technologies,e.g.,monocyte activation test(MAT),recombinant factor C bacterial endotoxin test(rFC BET),for detecting endotoxin/pyrogen,which have also made some progress in other fields(neurovirulence,adventitious agents,potency and immunogenicity,specific toxicity).The further development of 3Rs quality control approaches is facing some common challenges,such as the lack of international harmonized regulatory,standards and technical validation guidelines,how to scientifically evaluate the comparability and relevance of different testing technologies,and how to promote and popularize advanced testing technologies globally.

关 键 词：替代 优化 减少 生物制品 疫苗 

分 类 号：R979.9[医药卫生—药品]