摘要
目的建立洁净区微生物数据库,为追溯洁净区微生物污染来源提供依据,为无菌药品生产过程控制提供有力指导。方法对乙型脑炎减毒活疫苗生产车间洁净区环境和操作人员进行微生物负载检测,并对该车间注射用水、纯化水系统样品进行微生物限度检测,鉴别研究相应分离菌,建立洁净区微生物数据库。同时对乙型脑炎减毒活疫苗中间产品进行无菌检查检测,并对阳性结果分离菌进行鉴别分析。然后根据建立的洁净区微生物数据库对阳性结果举例进行溯源探讨分析。结果洁净区环境和人员主要存在里拉/藤黄微球菌、人葡萄球菌、表皮葡萄球菌以及科氏葡萄球菌科氏亚种等革兰阳性菌和蜡样芽胞杆菌等,水系统中则主要存在少动鞘氨醇单胞菌和铫子芽胞杆菌等。中间产品无菌阳性结果主要存在里拉/藤黄微球菌、蜡样芽胞杆菌以及奇异变形菌等,经调查分析,分别为操作过程中经环境偶然带入或试验动物操作不慎带入。结论建立洁净区微生物数据库是追溯产品微生物污染来源的有效方法,能够为无菌药品GMP生产过程制定有效的控制措施提供依据,并使其更有针对性。
Objective Provide the basis of finding the microbiological contamination sources, and give an effective guidance for the manufacturing process-control for sterile medicinal products. Method The environmental and personnel monitoring were performed in the clean areas of workshop on manufacturing Japanese encephalitis vaccine, Live and the microbial limit test was performed for WFI （water for injection） and purified water system samples on the same areas as well. Then charac- terize the isolates recovered from those tests above and establish a database of the microorganisms found in the clean areas. Meanwhile, the sterility test was used for intermediate products, and the isolates which were recovered from positive results were characterized. Some typical positive results were analyzed from samples according to the established database. Results Bacillus cereus and Gram-positive bacteria such as micrococcus luteus/lylae, staphylococcus hominis, staphylococcus epider- midis and staphylococcus chhnii ssp. cohnii were mainly found in clean rooms. Sphingomonas paucimobilis and brevibacillus choshinensis were mainly found in water system. There were mainly micrococcus luteus/lylae, bacillus cereus and proteus mirabilis for the positive results of the intermediate products, and they were taken into the intermediate products through acci- dentally operations in the environment or in animal test. Conclusion The established microorganism database for clean areas is an effective control method of finding the retrospective sources of microbial contamination related to products, it can provide an effective GMP manufacturing process-control for sterile medicinal products and make it more targeted.
出处
《微生物学免疫学进展》
2013年第3期33-36,共4页
Progress In Microbiology and Immunology
