黄热病减毒疫苗单一收获液无菌检查超限度结果的调查分析

Investigation and analysis on out of specification result in yellow fever attenuated vaccine single harvest sterile test

目的 鉴定黄热病减毒疫苗单一收获液无菌检查的阳性样品,对无菌检查超限度(out of specification,OOS)结果进行溯源分析,建立OOS调查的操作规程。方法 采用直接接种法对6瓶黄热病疫苗收获液进行无菌检查,发现1例阳性。分离纯化阳性样品得到污染物,用革兰染色法和全自动细菌鉴定仪进行鉴定。参照现行的药品质量管理规定中的OOS调查方法,分析可能引入微生物污染的相关因素。结果 第3天起,S6样品在不同培养基中均出现浑浊。阳性样品中污染物鉴定为革兰阳性粪肠球菌。OOS调查结果表明检出菌并非实验室检查过程带来的污染。结论 初步建立了无菌检查OOS的分析方案。

Objective To identify positive sample in sterile test of yellow fever attenuated vaccine single harvest,and retrospectively analyze out of specification(OOS)results to explore the standard operating procedures for the investigation of OOS results.Methods Aseptic examination was performed on 6 bottles of yellow fever attenuated vaccine single harvests by direct inoculation and found 1 positive.The contaminants isolated and purified were identified with gram staining and automatic bacterial identification instrument.Following the OOS investigation guidance in current drug quality regulations,the related factors that may lead to microbial contamination were analyzed step by step.Results Starting on day 3,sample S6 growing in different media became turbid.The contaminant in positive sample was identified to be gram positive bacterium Enterococcus faecalis.The OOS investigation showed that the bacteria were not polluted by laboratory test.Conclusion A preliminary analysis scheme of OOS for sterile test is established.