摘要
目的为制药企业和研发机构选择容器密封完整性检测方法和仪器提供参考。方法根据第41版《美国药典》第1207章,分别选择3种"确定性泄漏检测方法("真空衰减法、高压放电法、顶空气体激光法)和2种"概率性泄漏检测方法("微生物浸入法、色水法)检测同一组无菌阴性样品,对比不同容器密封完整性检测方法的差异。结果2种概率性检测方法中,色水法检测灵敏度较低,稳定性较差,但操作简单,仪器成本低;微生物浸入法检测结果可信度较高,无须单独采购特殊仪器,普通微生物实验室即可完成,但结果的重复性较差;2种方法均为破坏性试验,对于小批量产品或高价值产品不太适用。3种确定性检测方法结果的重复性较好,检测灵敏度较高,检测过程对产品无损伤,既适合离线抽样检测,也适合整合到生产线进行100%在线检测,但检测仪器的成本及后期计量维护的要求均较高。结论5种不同检测方法各有特点,选择时要综合考虑产品的实际情况和不同国际市场的监管要求。
Objective To provide a reference for pharmaceutical enterprises and research and development institutions to select methods and instruments for container-closure integrity test(CCIT).Methods According to the Chapter 1207 of United States Pharmacopeia(41st Edition),three deterministic leak test technologies(vacuum decay,high voltage leak detection,and lased-based headspace analysis)and two probabilistic leak test technologies(microbial challenging,liquid immersion and liquid tracer)were selected to test the sterile negative samples in the same group.Results Among the two probabilistic leak test technologies,the liquid tracer method had low sensitivity and poor stability,but the operation was simple and the instrument cost was low;the results of microbial challenging method had high reliability,and ordinary microbial laboratory could complete the test without purchasing special instruments,but the reproducibility of the results was poor.And the two methods were destructive tests,which were not suitable for small-batch products or high-value products.The results of the three deterministic leak test technologies were reproducible and sensitive,and the test process had no damage to the product.They were suitable for offline sampling test and 100%online test integrated into the production line,but the cost of test instruments and the requirements of later measurement maintenance were high.Conclusion The five different test methods have their own characteristics,when choosing the test methods should be based on the properties of products as well as the regulatory requirements of different international markets.
作者
封二飞
张筱宜
赵明
FENG Erfei;ZHANG Xiaoyi;ZHAO Ming(School of Pharmaceutical Sciences,Capital Medical University,Beijing,China 100069)
出处
《中国药业》
CAS
2021年第14期51-54,共4页
China Pharmaceuticals
基金
国家科技重大专项[2018ZX09721003-002-005]。
关键词
无菌药品
容器密封完整性检测
确定性泄漏检测方法
概率性泄漏检测方法
sterile drug
container-closure integrity test
deterministic leak test technologies
probabilistic leak test technologies
