流感病毒裂解疫苗裂解剂去除工艺改进及稳定性研究

目的改进流感病毒裂解疫苗裂解剂去除工艺，降低残余卵清蛋白和裂解剂含量，提高疫苗质量，降低成本。方法分别将A1、A3和B型流感病毒纯化液用磷酸缓冲液（PB）沉淀法去除裂解剂，经超滤、除菌制备原液，配制6批半成品，其中3批不含硫柳汞，3批含硫柳汞，经全面检定，并观察放置37℃、25℃和2～8℃不同时间的稳定性。结果该疫苗各项指标均符合《中国药典》（2010年版）三部要求，其中卵清蛋白平均为3．83ng／mL，裂解剂平均为57μg／mL，比改进前分别降低97．9％和69％。37℃放置4周、25℃3个月及2-8℃12个月后检定全部合格。结论该工艺步骤简单，去除卵清蛋白和裂解剂效果明显，是进一步提高疫苗质量和降低成本的有效工艺。

Improvement of splitting reagent removal procedure and stability of influenza virus split vaccine

Objective To improve splitting reagents removal procedure for influenza virus vaccine, reduce the residual ovalbumin and splitting reagents content, improve vaccine quality and reduce costs. Method Splitting reagents in the A1, A3 and B purified influenza virus solution were removed by phosphate buffer （ PB ） precipitation. Bulk was produced by sterilized by ultrafiltration of virus solution. Six batches of final bulk were prepared, including three batches with thimerosal and another three batches without thimerosal. Then a comprehensive test was proceeded to observe the stability of vaccine placed at 37 ~C, 25 ~C and 2-8 ~C for different time. Result The indicators of vaccine are consistent with ＂ Chinese Pharmacopoeia＂ third （2010） edition requirements, including ovalbumin averaged 3.83 ng/mL, and splitting reagents av- eraged 57 pμg/mL, they are decreased by 97.9% and 69%, respectively. The vaccines are all qualified at 37 °C for 4 weeks, 25 °C for 3 months or 2-8 ~C for 12 months. Conclusion This procedure has simple steps to remove the splitting reagents and ovalbumin effectively, it is a valid orocedure for imoroving the uualitv and reducing the cost of the vaccine.