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

The Optimization of Aaluminum Hydroxide Adjuvant Processing in the Production of Inactivated Enterovirus 71 Vaccines

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 m L,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 ol inactivated enterovirus 71 vaccines. Methods： Preparing aluminum hydroxide adjuvant with ammonia- water 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 af- ter optimization were compared by size testing, sedimentation analysis, ammonium ion testing, alumi- num content testing and aluminum adsorption effect testing. Results： The average size of aluminum hy- droxide adjuvant after optimization was markedly smaller than before （P 〈 0.05 ）, as well as the varia- tion 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 hy-droxide adjuvant（P 〈0.05 ）. Conclusion： The improvement of the technique might increase the qual- ity 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.