FⅢ制作工艺优化对静注人免疫球蛋白(pH4)收率和关键质量指标的影响分析

Effect of FⅢ process optimization on the yield and key quality indexes of intravenous immunoglobulin

目的优化静注人免疫球蛋白(pH4)FⅢ制作工艺参数,保证产品质量的同时,提高产品收率。方法将FⅡ+Ⅲ沉淀溶解后的乙酸钠、醋酸缓冲液和乙醇的加液时间分别由4 h、2 h、4 h延长为5 h、3 h、5 h;FⅡ+Ⅲ沉淀溶解温度由-0.5℃提高至1℃,FⅢ制作温度由-5.5℃提高至-5.0℃;对优化前后的人免疫球蛋白原液收率和关键质量指标(纯度、分子大小分布、抗补体活性、Fc生物学活性和激肽释放酶原激活剂)进行统计分析。结果加液时间延长和温度提高分别使人免疫球蛋白原液收率提高了19.6%和12.9%,且关键质量指标均未发生显著变化。结论 FⅢ制作过程加液时间和温度参数的优化,有效提高了人免疫球蛋白原液收率,未影响产品质量。

Objective To increase the yield of intravenous immunoglobulin by optimizing the FⅢ production process, under the premise of ensuring product quality. Methods The adding time of sodium acetate, acetic acid buffer and ethanol was adjusted from 4 h, 2 h and 4 h to 5 h, 3 h and 5 h, respectively. The temperature of FⅡ+Ⅲ precipitation dissolved was increased from-0.5℃ to 1℃, and FⅢ production temperature was increased from-5.5℃ to-5.0℃. The yield and key quality indexes(including purity, molecular size distribution, anti-complement activity, biological activity of Fc fragment and PKA) of human immunoglobulin concentrate before and after optimization were statistically analyzed. Results The yield of human immunoglobulin concentrate increased by 19.6% and 12.9%,respectively, with the prolongation of adding time and the increase of temperature, while the key quality indexes did not change significantly. Conclusion Optimizing parameters of solution adding time and temperature in FⅢ manufacturing process can effectively improve the yield of human immunoglobulin concentrate without affecting the key quality index.