全层析工艺制备10%静注人免疫球蛋白及检测分析

Characterizations And Analysis of 10% IVIG Prepared by Chromatography

目的试验研究全层析法结合超滤透析等步骤,并辅以3步病毒灭活/去除工艺制备10%静注人免疫球蛋白的可行性。方法运用全层析工艺纯化制备10%IVIG,计算工艺回收率,并参照《中华人民共和国药典》及《欧洲药典》8.0静注人免疫球蛋白质量标准对其关键指标进行了检测;用散射比浊法对终产品Ig A、Ig M杂质蛋白及Ig G亚类等指标进行检测分析。结果 Ig G总回收率平均值为60.86%,变异系数为0.7%表明工艺具有良好的重复性;纯度、分子大小分布等关键指标到达《中华人民共和国药典》及《欧洲药典》8.0要求;杂质蛋白Ig A、Ig M含量较低,Ig A<2.87 mg/L、Ig M<0.15 mg/L;4个亚类构成比(%)分别为55.1±2.5、35.8±2.3、5.39±0.93和3.66±0.16。结论本公司全层析工艺能高效制备满足国际标准的10%IVIG产品。

Objectives This study aims to assess the feasibility to prepare 10% IVIG using a series of separations per- formed by chromatography and UF/DF with a three-phase virus inactivation/removal protocol. Methods 10% IVIG was pre- pared by chromatography, and the final products were characterized according to both Chinese and European Pharmacopoeia （8.0）. The BN ProSpec System was adopted to detect contaminating proteins（IgA,IgM） and IgC subtypes. Results The IgG recovery rate was 60. 86% with a variation coefficient of 0. 7%, indicating that the process was stable. 10% IVIG obtained in this study cleared all critical compendial tests. The impurity profile fell into the lower level range： IgA〈2. 87 mg/L, IgM〈0. 15 IgC. IgG subtype components ratio（%） of the final products are as follows, IgG1 ： 55.1±2. 5,IGG2：35.8±2.3, IgG3：5.39±0. 93, IgC,4：3.66±0. 16. Conclusion The preparation of high quality 10% IVIC is achieved by this novel ap- proach with a high recovery rate from human plasma.