微生物挑战法测定注射剂药品包装容器密封完整性  

Determination of the container closure integrity for injection packaging via the microbial ingress test method

作　　者：王静 黄思嘉 王妮 张芳芳 WANG Jing;HUANG Si-jia;WANG Ni;ZHANG Fang-fang(Shanghai Food and Drug Packaging Material Control Center,Shanghai 201203,China)

机构地区：[1]上海市食品药品包装材料测试所,上海201203

出　　处：《药物分析杂志》2023年第7期1213-1220,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：国家药典委员会药包材密封性完整性指导原则课题项目(2019Y04)。

摘　　要：目的:对微生物挑战法在注射剂药品包装系统密封完整性检测中的灵敏度进行研究与讨论。方法:选择中性硼硅玻璃注射剂瓶和5层共挤输液用袋2种较为典型的“刚性”和“柔性”注射剂药品包装系统,分别通过激光打孔和微量管制备的方法制作不同尺寸缺陷的阳性样品后在加压条件下进行微生物挑战试验。通过二分类Logistic回归方法对不同孔径阳性样品的泄漏情况进行统计分析。结果:采用本研究建立的微生物挑战法模拟条件进行试验时,中性硼硅玻璃注射剂瓶的检测灵敏度为2μm, 5层共挤输液用袋的检测灵敏度为1.5μm。结论:不同注射剂包装系统可通过适宜方法制备不同尺寸缺陷阳性样品模拟泄漏情况,并通过密闭容器加压模拟实际运输等条件进行浸没式微生物挑战试验。采用二分类Logistic回归统计分析可以对不同包装系统采用浸没式微生物挑战法进行密封完整性检测时的灵敏度进行确定,为包装容器密封完整性检查方法的关联比较研究提供技术基础。Objective:To investigate the sensitivity of the microbial ingress test method in container closure integrity detection for injection packaging system.Methods:Two typical rigid and soft injection packaging systems,the borosilicate glass vials and five-layer copolymerized compound membrane infusion bags were selected.The positive samples of defects of different sizes were laser-drlled and penetrated through by planting micro-tubes,respectively,and then subject to the microbial ingress test under a pressure condition.Binary Logistic regression method was used to assess the leakage.Results:Using the simulated conditions of microbial ingress test method established in this study,the detection sensitivity of 2μm for the vials and 1.5μm for the infusion bags.Conclusion:Leakage simulation of different injection packaging systems can be achieved by preparing defect positive samples of different sizes with proper approaches and submerged microbial ingress test method is carried out by pressurzing the closed container to simulate an actual transportation condition.Binary Logistic regression statistical analysis can be used to determine the sensitivity of submerged microbial ingress test method in container closure integrity detection for different injection packaging systems,which helps to lay a technical foundation for correlative comparisons with container closure integrity inspection methods for packaging.

关 键 词：密封完整性 微生物挑战法 一致性评价 灵敏度 注射剂包装系统 无菌保障 

分 类 号：R917[医药卫生—药物分析学]