疫苗类制品无菌检查方法(薄膜过滤法)的研究

目的: 疫苗制品的无菌检查方法中薄膜过滤法的建立和方法学验证。 方法: 选取5个企业21个品种的疫苗制品,采用薄膜过滤法进行无菌检查,选取金黄色葡萄球菌、枯草芽孢杆菌、大肠埃希菌、生孢梭菌、白色念珠菌和黑曲霉作为验证菌进行方法学验证。 结果: 实验结果表明,疫苗类生物制品对真菌的抑菌作用较细菌更弱,疫苗类生物制品的敏感菌株为枯草芽孢杆菌,含防腐剂硫柳汞的疫苗的抑菌作用较其他类的疫苗更强。采用薄膜过滤法进行试验时,某些疫苗样品由于含氢氧化铝佐剂而不易通过薄膜,可将稀释液更换为磷酸盐缓冲液(pH 6.0),可使其顺利通过滤膜。 结论: 按照不同疫苗制品的特性,将其大致分为三类,并分别建立了无菌检查法。

Objective: To establish the method validation of method for sterility test of vaccines using the technique of membrane filtration. Method: 21 vaccines from 5 manufacturers were selected for sterility test using the technique of membrane filtration.Six validation strains,such as Staphylococcus aureus,Bacillus subtilis,Escherichia coli,Clostridium sporogenes,Candida albicans and Aspergillus niger, were used for the verification of sterility test. Results: It is indicated that antibacterial activity of fungi was less than that of bacterium,and the sensitive one was Bacillus subtilis. The vaccines which contain merthiolate have more antibacterial activity than that have none.It is difficult for some vaccines to filtrate the membrane because they contained aluminium hydroxide.It can be solved by using the Phosphate buffer (pH 6.0) as diluent. Conclusions: Vaccines were divided three classes by different characteristics,and method of sterility test for each of vaccines was established.