肠道病毒71型灭活疫苗纯化用层析介质使用寿命的确定

Determination of the chromatography media life for enterovirus 71 inactivated vaccine purification

目的探索肠道病毒71型灭活疫苗纯化用层析介质最佳使用次数。方法在规模化生产过程中，根据层析介质特性采用相应的清洗和消毒方式。在保证产品质量的前提下，综合考虑生产过程中相关参数及层析介质柱效，评估层析介质使用寿命。结果随着层析介质使用次数的增多，纯化运行过程中层析介质的压力存在上升趋势，表明出现了污染物的聚集；同时层析柱的每米理论塔板数降低、对称性因子偏离，表明污染物在层析介质中的聚集造成了填料分布不匀，导致分离效果下降。经过综合评估，将凝胶过滤层析介质和离子交换层析介质的纯化使用次数暂定为62和32次。结论初步确定了层析介质的使用寿命，为规模化生产中层析介质的使用和更换提供了理论依据。

Objective To determine the optimum number of usages for chromatography media in human enterovirus 71 inactivated vaccine purification. Methods In large-scale production, different cleaning methods were used to clean and disinfect corresponding chromatography media according to media characteristics. On the premise of guaranteeing product quality, the service life of the chromatography media was evaluated based on related parameters and column efficiency. Results With the usage of chromatography media increasing, the pressure of media was rising during purification process, indicating the accumulation of pollutants. Meanwhile, column theoretical plate number per meter decreased and the symmetry factor deviated. The uneven packing distribution caused by accumulation of contaminants in media resulted in decrease of separation efficiency. Through comprehensive evaluation, the usage numbers of gel filtration and ion-exchange chromatography media in large-scale production were determined as 62 and 32, respectively. Conclusion The service life of chromatography media has been preliminarily determined, providing theoretical basis for the use and replacement of chromatography media in large-scale production.