摘要
目的评价Sabin株脊髓灰质炎灭活疫苗(inactivated poliomyelitis vaccine made from Sabin strains,sIPV)制剂处方优化后产品质量。方法对制剂处方优化(无酚红、无抑菌剂)后sIPV产品进行质量属性评估,并与已上市sIPV产品进行质量可比性分析;将制剂处方优化前后成品同时肌内免疫270只Wister大鼠(雌雄各半),检测大鼠血清中和抗体水平,进行免疫原性评价和可比性分析;将制剂处方优化后成品分别置37℃、室温(20~25℃)和2~8℃进行加速和长期稳定性试验,检测关键指标D抗原含量,进行稳定性评价,并与已上市产品历史数据进行可比性分析。结果制剂处方优化后的sIPVⅠ、Ⅱ、Ⅲ型D抗原含量、蛋白质含量、pH、Vero细胞蛋白质残留量、牛血清白蛋白残留量、Vero细胞DNA残留量、游离甲醛含量等各项检定结果均符合《中国药典》三部(2020版)要求和企业标准,工艺优化前后质量属性一致,免疫原性一致,加速及长期稳定性趋势一致。结论制剂处方优化后的sIPV不再含有酚红和抑菌剂成分,制剂安全性得到提升;与优化前相比,产品质量属性、免疫原性及稳定性高度相似;产品有效期内各项指标均符合要求,且具有良好的稳定性。
Objective To evaluate the product quality of inactivated poliomyelitis vaccine made from Sabin strains(sIPV)after optimization of preparation formula.Methods The quality attributes of sIPV products after preparation optimization(no phenol red and no bacteriostatic agent)were evaluated,and the quality comparability with the listed sIPV products was analyzed;270 Wister rats of half male and half female were immunized with the finished products before and after preparation optimization simultaneously by intramuscular injection,measured for the level of neutralizing antibody in serum,evaluated for the immunogenicity,and analyzed for the compa-rability;The finished products with optimized preparation were placed at 37℃,room temperature(20~25℃)and 2~8℃ for accelerated and long-term stability tests separately,detected for the content of key indicator D antigen to evaluate the stability,and analyzed for the comparability with historical data of the listed products.Results After preparation formula optimization,the detection results of the sIPV vaccine for type Ⅰ,Ⅱ,and Ⅲ D antigen content,protein content,pH value,Vero cell protein residue,bovine serum albumin residue,Vero cell DNA residue,and free formaldehyde content all conformed to the requirements of Chinese Pharmacopoeia Ⅲ(2020 edition)and the enterprise standard.Before and after the process optimization,the quality attributes,immunogenicity and accelerated and long-term stability trends were consi-stent.Conclusion The formulation of the optimized sIPV vaccine no longer contains phenol red and bacteriostatic agent ingredients,of which the safety has been improved;The quality attributes,immunogenicity,and stability of the product are highly similar to those before optimization;All indicators met the requirements during the validity period and the product has good stability.
作者
李婉莉
刘英微
李艳
董圆
李爱灵
赵玉秀
LI Wanli;LIU Yingwei;LI Yan;DONG Yuan;LI Ailing;ZHAO Yuxiu(The Second Laboratory of Vaccine Research,Beijing Institute of Biological Products Co.,Ltd.,Beijing 100176,China)
出处
《中国生物制品学杂志》
CAS
CSCD
北大核心
2023年第11期1353-1360,共8页
Chinese Journal of Biologicals
基金
国家科技重大专项重大新药创制(2018ZX09737-003)。
关键词
Sabin株脊髓灰质炎灭活疫苗
制剂
优化
产品质量
免疫原性
稳定性
可比性
Inactivated poliomyelitis vaccine made from Sabin strains(siPV)
Preparation
Optimization
Product quality
Immunogenicity
Stability
Comparability
