吸附无细胞百白破-重组乙型肝炎(CHO细胞)联合疫苗的中试工艺

Pilot Production Procedure of Adsorbed Acellular DTP-Recombinant Hepatitis B(CHO Cells)Combined Vaccine

目的探讨吸附无细胞百白破-重组乙型肝炎(CHO细胞)联合疫苗(DTaP-HBV)的中试工艺。方法通过不同的配比条件,探索DTaP-HBV联合疫苗的最佳中试工艺。以此工艺制备3批DTaP-HBV,进行各项指标的检定及稳定性试验。结果配方以无细胞百日咳疫苗原液18μgPN/ml,精制白喉类毒素25Lf/ml,精制破伤风类毒素7Lf/ml,重组乙肝疫苗原液20μg/ml为宜;DTaP-HBV的稀释液选用0.85%NaCl溶液吸附效果较好,各抗原间无干扰作用;不同配合方式对四联疫苗的效力影响不大。3批DTaP-HBV的各项检定指标均符合《中国药典》三部(2005版)要求,且稳定性良好。结论已筛选出DTaP-HBV联合疫苗的最佳中试工艺,以此工艺制备的疫苗安全、稳定、有效。

Objective To develop a pilot production procedure of adsorbed acelluar DTP-recombinant hepatitis B（CHO cells）combined vaccine（DTaP-HBV）.Methods The formula of DTaP-HBV was optimized,based on which a pilot production procedure was developed.Three batches of DTaP-HBV were prepared by the procedure and subjected to quality control and stability tests.Results The optimal formula of DTaP-HBV consisted of 18 μg PN /ml bulk of acellular pertussis vaccine,25 Lf /ml purified diphtheria toxoid,7 Lf /ml purified tetanus toxoid and 20 μg /ml bulk of recombinant HB vaccine.The sodium chloride solution at a concentration of 0.85% was selected as diluent,which showed good adsorption effect,while no interference between antigens was observed.The method for formulation showed no significant effect on the potency of DTaP-HBV.All the 3 batches of prepared DTaP-HBV showed good stability,and their quality indexes met the requirements in Chinese Pharmacopoeia（VolumeⅢ,2005 edition）.Conclusion A pilot production procedure of DTaP-HBV was developed,and the prepared vaccine was safe,stable and effective.