制药企业CNC区域微生物数据库的建立及微生物种群分析  

Establishment of CNC regional microbial database and microbial population analysis for pharmaceutical enterprises

作　　者：张弛 张建玲 薛梅 律苗 李泷 李勤勤 ZHANG Chi;ZHANG Jianling;XUE Mei;LV Miao;LI Shuang;LI Qinqin(Department of Quality Inspection,Beijing Institute of Biological Products Co.,Ltd.,Beijing 100176,China)

机构地区：[1]北京生物制品研究所有限责任公司质量检定室,北京100176

出　　处：《中国生物制品学杂志》2023年第12期1503-1507,1514,共6页Chinese Journal of Biologicals

基　　金：发展中国家疫苗生产商联盟(DCVMN)资助课题(202011231426)。

摘　　要：目的建立制药企业CNC(controlled not classified)区域(即受控但未分级区域)微生物数据库,与洁净区微生物分布进行关联分析,实现对洁净区尤其是核心无菌操作区域的良好微生物控制,提升制药企业的无菌保障水平。方法以1个制药企业生产车间的CNC区域为研究对象,按照人员、物料进入洁净区的路线,逐个对CNC区域进行浮游菌、沉降菌、人员和环境表面微生物取样。微生物经培养、纯化后,采用16S rRNA测序法进行菌种鉴别。利用Microbiomeanalyst在线分析软件进行数据分析。结果制药企业CNC区域微生物数量和种类丰富,共收集到4080株微生物,分布在47个属内。革兰阳性菌占比达84.4%,主要为葡萄球菌属、微球菌属、微杆菌属;革兰阴性菌占比达15.6%,不动杆菌属是分布数量最大的革兰阴性菌。以Alpha多样性指数表征微生物种群丰富度,浮游菌、沉降菌的微生物种群丰富度最高,环境表面次之,人员表面微生物种群丰富度最低。人员帽兜和胸腹部微生物数量相对较少,脚底和手部微生物数量较多。人员表面微生物种类相对较少,且葡萄球菌占据绝对优势。CNC区域微生物分布与同生产车间B、C级洁净区微生物分布进行关联分析,B、C级洁净区收集到的微生物绝大部分包含在CNC区域微生物种群中。B、C级洁净区与CNC区域类似,均以葡萄球菌属、微球菌属为主。不动杆菌属在B、C级洁净区的分布比例较CNC区域有所下降。结论建立了制药企业CNC区域微生物数据库,确定了易进入洁净区的微生物种群,为洁净区的良好微生物控制提供了可靠的技术支持。Objective To establish CNC(controlled not classified)area microbial database of pharmaceutical enterprises,conduct correlation analysis with microbial distribution in clean area to achieve good microbial control in the clean area,especially in the core aseptic operation area,and improve the sterility assurance level of pharmaceutical enterprises.Methods The CNC area of a manufacturing workshop from pharmaceutical enterprise was selected as the research object,the airborne microbe,settling microbe,personal and environmental surface microorganisms were sampled one by one in the CNC area according to the route of personnel and materials entering the clean area.After the microorganisms were cultured and purified,the 16S rRNA sequencing method was used to identify the strains.Microbiomeanalyst online analysis software was used for data analysis.Results The number of microorganisms in the CNC area of pharmaceutical enterprises was large and the species were rich.A total of 4080 microorganisms were collected,which distributed in 47 genera.Gram-positive bacteria accounted for 84.4%,mainly belonging to Staphylococcus,Micrococcus,Microbacterium.Gram-negative bacteria accounted for 15.6%,and the distribution of Acinetobacter was much higher than other gram-negative bacteria.The Alpha diversity index was used to characterize the richness of microbial populations.The richness of microbial populations of airborne microbe and settling microbe was the highest,followed by environmental surface microorganisms,and the microbial population richness of personnel surface microorganism was the lowest.The number of microorganisms in the personnel's hood and chest was relatively small,and the number of microorganisms in the personnel's soles of feet and hands was relatively large.There were relatively few types of microorganisms on the surface of personnel,and staphylococcus showed an absolute advantage.The microbial distribution in CNC area was correlated with the microbial distribution in Class B and C clean areas of the same productio

关 键 词：制药企业 CNC区域 微生物分布 洁净区 

分 类 号：Q93[生物学—微生物学]