人免疫球蛋白生产工艺对多聚体含量影响的研究

Effect of human immunoglobulin manufacturing process on polymer content

目的考察人免疫球蛋白在工艺中多聚体含量的变化规律,重点考察pH值与人免疫球蛋白多聚体含量之间的关系,为人免疫球蛋白类产品多聚体控制提供依据。方法取静注人免疫球蛋白(IVIG)和乙型肝炎人免疫球蛋白(HBIG)低pH中间品,用0.5 mol/L HCl或0.1 mol/L HCl调节不同梯度pH值,再用HPLC测定多聚体含量,观察和分析不同pH值对多聚体含量变化的影响。结果在低pH条件下,人免疫球蛋白样品中的多聚体含量随pH值的降低从<1%升高至10%左右,当pH值在3.85~3.10时,样品多聚体含量随pH值的降低从0.38%~15.5%呈现指数上升的趋势,多聚体含量的对数与pH为线性关系。结论在低pH值条件下,pH值对人免疫球蛋白的多聚体含量有显著的影响,建议人免疫球蛋白生产工艺全过程pH应保持在4.0以上。

Objective To investigate the changing pattern of polymer content in the manufacturing process of human immunoglobulin, especially the correlation between pH value and polymer content, so as to provide basis for the control of polymer in human immunoglobulin products. Methods IVIG and HBIG low pH intermediate samples were taken and their pH values were adjusted to different gradients with 0.5 or 0.1 mol/L HCl. The polymer content was detected by HPLC, and the influence of different pH values on polymer content was observed and analyzed. Results With low pH value, the polymer content of samples increased from <1% to 10% with the decrease of pH value. When pH value was in the range of 3.85~3.10, the polymer content in the samples increased from 0.38% to 15.5% exponentially with the decrease of pH value. The logarithm of polymer was linearly correlated with pH value. Conclusion When pH value is low, polymer content of human immunoglobulin is significantly affected by pH value. Keeping pH value above 4.0 during the whole manufacturing process of human immunoglobulin is suggested.