论文部分内容阅读
目的评价重组戊型肝炎疫苗原液的长期稳定性。方法将连续3批重组戊型肝炎疫苗原液置(-20±2)℃保存12个月,分别于第0、3、6、9和12月取样,依据《中国药典》第三部和第四部(2015版)和《重组戊型肝炎疫苗制造及检定规程(暂定)》规定进行无菌检查、蛋白含量、纯度、相对分子质量、等电点和细菌内毒素检测及紫外光谱扫描;第6和12月,分别将3批原液配制成疫苗进行效力测定。结果 3批疫苗原液在各时间点无菌检查均为阴性,细菌内毒素含量均小于5 EU/ml,蛋白含量在3.47~3.81 mg/ml,单体及二聚体总量在96.0%以上,二聚体占总蛋白的85%~100%,单体相对分子质量为19 500~19 700,等电点检查主区带在4.05~5.80之间,紫外光谱扫描最大吸收峰在(278±3)nm,3批原液第6和12月的效力ED_(50)值≤1.0μg,均符合暂定制检规程。结论重组戊型肝炎疫苗原液在(-20±2)℃可稳定存放12个月,本研究为原液的存放效期提供了可靠的数据支持。
Objective To evaluate the long-term stability of recombinant hepatitis E vaccine stock solution. Methods Three consecutive batches of recombinant hepatitis E vaccine were stored at -20 ± 2 ℃ for 12 months. Samples were collected at 0, 3, 6, 9 and 12 months respectively. According to the third and fourth Chinese Pharmacopoeia (2015 edition) and the “recombinant hepatitis E vaccine manufacturing and testing procedures (Provisional)” for sterile inspection, protein content, purity, relative molecular mass, isoelectric point and bacterial endotoxin testing and UV spectral scanning; In June and December, three batches of stock solution were formulated into a vaccine for potency determination. Results The results showed that all the three batches of vaccine solutions were negative for bacteriological examination at all time points. The bacterial endotoxin contents were all less than 5 EU / ml, the protein contents were 3.47-3.81 mg / ml, the total monomer and dimer contents were above 96.0% Dimer accounted for 85% ~ 100% of the total protein, monomer relative molecular mass of 19 500 ~ 19 700, the isoelectric point of the main zone in the 4.05 ~ 5.80, UV absorption peak in the (278 ± 3 ) nm. The efficacy values of ED_ (50) in the 6th and 12th month of the 3 batches of crude liquid were less than or equal to 1.0μg, all of which were in accordance with the tentative inspection rules. CONCLUSION: The recombinant HEV vaccine stock solution can be stably stored for 12 months at (-20 ± 2) ℃. This study provides reliable data for the storage of stock solution.