冻干b型流感嗜血杆菌结合疫苗强制降解的稳定性研究

Stability study on freeze-dried Haemophilus influenzae type b conjugate vaccine by forced degradation

目的 通过强制降解试验观察冻干b型流感嗜血杆菌(Haemophilus in fluenzae type b, Hib)结合疫苗在高温、高湿、强光照射下的稳定性,为疫苗生产工艺、包装材料和贮存条件的确定提供科学依据.方法 分别采用40℃温度、(75±5)%相对湿度、(4 500±500)lx光照处理冻干Hib结合疫苗,取样,按中国药典2015年版三部的要求进行疫苗的全部项目检测.结果 冻干Hib疫苗经40℃处理10d,水分由2.0%上升至2.9%,多糖分子大小(分配系数<0.2的洗脱液回收率)由94%下降至85%,但两者仍分别符合≤3.0%和>60%的质量标准;而高分子结合物含量由87%降至75%,已不符合≥80%的质量标准.(75±5)%相对湿度和(4 500±500) lx光照处理10d对疫苗的影响不明显,疫苗质量指标仍符合规定.结论 高温是影响冻干Hib结合疫苗稳定性的主要因素.

Objective To observe stability of freeze-dried Haemophilus influenzae type b (Hib) conjugate vaccine under high temperature,high relative humidity and strong light with compulsory degradation tests,and provide scientific basis for determination of vaccine production process,packaging materials and storage conditions.Methods The freeze-dried Hib conjugate vaccine was treated with 40 ℃ temperature,(75 ± 5) % relative humidity or (4 500 ± 500) lx light.Then vaccine was sampled and tested for all items according to Chinese pharmacopoeia (2015 edition,volume [Ⅲ).Results After 10 d at 40 ℃,the water content of the vaccine increased from 2.0% to 2.9%,and the molecular size of polysaccharide (recovery rate of elute with distribution coefficient <0.2) decreased from 94% to 85%,but still met quality standards of ≤3.0% and >60%,respectively.The content of high molecular weight conjugates decreased from 87% to 75%,failing to meet the quality standard of ≥80%.The effect of (75±5)% relative humidity and (4 500± 500) lx light irradiation for 10 d on the vaccine was not obvious,and the quality of the vaccine was still in line with requirements.Conclusion High temperature is the main factor affecting the stability of freeze-dried Hib conjugate vaccine.