肠道病毒71型灭活疫苗生产中氢氧化铝佐剂制备工艺优化

摘要

目的:对肠道病毒71型灭活疫苗生产工艺中氢氧化铝佐剂的制备工艺进行优化.方法:采用氨水法制备氢氧化铝佐剂,取优化前3批及优化后3批,对制备过程中氨水的滴加方式以及透析方式进行优化;检测优化前后的氢氧化铝佐剂的粒径、沉降率、铵离子及铝含量,同时检测优化前后各3批氢氧化铝对肠道病毒71型灭活疫苗的吸附效果.结果:优化后的氢氧化铝佐剂平均粒径显著小于优化前(P＜0.05),且平均粒径变异系数小于优化前3批,优化后3批氢氧化铝佐剂的沉降率均为0 mL,铵离子检测合格率100％,铝含量及氢氧化铝含量显著大于优化前(P＜0.05)、分别提高了24.7％和26.1％;优化前后6批氢氧化铝佐剂所配制的半成品,其上清液抗原百分含量均≤1.25％,优化前后的氢氧化铝佐剂对EV71抗原的吸附效果比较,差异无统计学意义(P＞0.05).结论:本部分的优化方式提高了自配氢氧化铝佐剂的质量和安全性,减少了批间差异,提高了生产效率,并且其有效性没有因为优化而受到影响.%Objective:To optimize the aluminum hydroxide adjuvant processing in the production of inactivated enterovirus 71 vaccines.Methods:Preparing aluminum hydroxide adjuvant with ammoniawater method.The items for optomizing including the way of dropping ammonia-water and dialysis method.The aluminum hydroxide adjuvant products of 3 batches before optimization and 3 batches after optimization were compared by size testing,sedimentation analysis,ammonium ion testing,aluminum content testing and aluminum adsorption effect testing.Results:The average size of aluminum hydroxide adjuvant after optimization was markedly smaller than before (P ＜ 0.05),as well as the variation coefficient was smaller than before.For the 3 batches after optimization,sedimentation rate was 0ml,and the ammonium ion testing was 100％ qualified.Aluminum and aluminum hydroxide contents were evidently more than before (P ＜0.05) increased by 24.7％ and 26.1％ respectively.For all of the semi-manufactures in the 6 batches,the antigen percentage in supernatant was ≤1.25％.There was no difference of adsorption effect to enterovirus 71 antigen among the 6 batches of aluminum hydroxide adjuvant(P ＜ 0.05).Conclusion:The improvement of the technique might increase the quality and safety of aluminum hydroxide adjuvant product,decrease batche variation,and increase the production efficiency.And the effectiveness of aluminum hydroxide adjuvant would not be affected.