注射用微球内部无菌检查法探讨  

Discussion on Methodology of Internal Sterility Test of Microspheres for Injection

作　　者：冯震 肖珊珊 陈辉 李静敏 唐黎明 杨美成 FENG Zhen;XIAO Shanshan;CHEN Hui;LI Jingmin;TANG Liming;YANG Meicheng(NMPA Key Lab.for Testing Technology of Pharmaceutical Microbiology,Shanghai Institute for Food and Drug Control,Shanghai 201203;Shanghai Livzon Pharmaceutical Co.,Ltd.,Shanghai 201206)

机构地区：[1]上海市食品药品检验研究院,国家药品监督管理局药品微生物检测技术重点实验室,上海201203 [2]上海丽珠制药有限公司,上海201206

出　　处：《中国医药工业杂志》2022年第12期1761-1768,共8页Chinese Journal of Pharmaceuticals

基　　金：2020年国家药品标准提高研究项目《特殊剂型无菌检测方法学研究》(编号2020Y05)。

摘　　要：注射用微球无菌检查既要关注“球外无菌”又要关注“球内无菌”,而检测的难点是“球内无菌”,即微球内部的无菌性检查。该研究在调研注射用微球生产工艺的基础上,选择代表性品种,模拟潜在微生物污染物存在条件下的微球溶解过程,建立了2种内部无菌检查方法:一是采用二甲基亚砜(DMSO)溶解微球;二是采用pH 10.0缓冲液溶解微球。2种方法制备的无菌检查供试液均以细菌耐受性芽孢作为试验菌,采用直接接种法进行无菌检查,并探讨供试液制备、试验用菌株、方法适用性等关键技术环节的科学性和合理性。该研究是注射用微球无菌检查方法开发和验证策略的有益探索,可为此类药物制剂的质量控制和标准提高提供研究思路和数据支撑。The close attention in sterility test of microspheres for injection should be paid to both external sterility and internal sterility,and the difficulty for the method establishment and validation was the internal sterility test.On the basis of investigating the production process,this study selected representative products of microspheres for injection and simulated the dissolution process of the microspheres in the presence of potential microbial contaminants,established two internal sterility inspection methods,one was to dissolve the microspheres in DMSO,and the other was to dissolve the microspheres with a pH 10.0 buffer solution.The sterility test was carried out by direct inoculation method,and the bacterial-tolerant spores were used as the strains of the test microorganisms.The key technical points,such as the solution to be tested,the strains of the test microorganisms and the method suitability test,were discussed.This study could provide a beneficial reference for the development and validation of sterility test for microspheres for injection.

关 键 词：注射用微球 无菌检查 方法适用性试验 质量控制 

分 类 号：R917[医药卫生—药物分析学]