静注人免疫球蛋白纯化用层析介质使用寿命的验证

Validation for service life of chromatographic media for purification of human immunoglobulin for intravenous injection

目的验证用于静注人免疫球蛋白生产的Fractogel®EMD TMAE(简称TMAE)层析介质的使用寿命。方法建立TMAE凝胶层析缩小模型,通过对层析介质运行过程中的层析图谱、蛋白回收率、IgA、IgM、分子大小分布、压力、理论塔板数、对称系数和总有机碳(total organic carbon,TOC)进行趋势分析。对每次层析过程中的参数进行比对,分析随着循环次数的增加关键参数的变化情况,确定层析介质使用寿命。结果IgA检测均值≤100μg/mL,IgM检测均值≤50μg/mL,IgG单体与二聚体含量之和>95.0%,均符合产品质量标准。层析介质的压力呈逐步升高的趋势,蛋白回收率下降,均在可接受范围内,同时层析柱的每米理论塔板数和对称系数符合使用要求。结论用于静注人免疫球蛋白生产的TMAE层析凝胶使用寿命暂定为240次。

Objective To verify the service life of Fractogel®EMD TMAE(TMAE in short)for purification of human immunoglobulin for intravenous injection.Methods A downsizing Fractogel®EMD TMAE model was established.The trend analysis was performed on the chromatogram,protein recovery,IgA,IgM,molecular size distribution,pressure,number of theoretical plates,symmetry coefficient and total organic carbon(TOC)during operation of the chromatographic medium.The parameters of each chromatography were compared to analyze the changes of key parameters with the increase of number of cycles and determine the service life of the chromatographic medium.Results The average measured values of IgA and IgM were not more than 100 and not more than 50μg/mL respectively,while the sum of IgG monomer and dimer contents were more than 95.0%,all of which met the product quality standard.The pressure of chromatographic medium showed a gradually increasing trend,while the protein recovery rate decreased,all of which were within the acceptable range.Meanwhile,the theoretical number of plates per meter and the symmetry coefficient of chromatographic column met the requirements for application.Conclusion The service life of TMAE for production of human immunoglobulin for intravenous injection was determined as 240 times temporarily.