低pH孵放病毒灭活处理对马破伤风免疫球蛋白F(ab')_2质量的影响
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摘要
目的考察低pH孵放病毒灭活处理对马破伤风免疫球蛋白F(ab')_2质量的影响。方法取马破伤风免疫球蛋白F(ab')_24份,分别调整pH至3.8、4.1、4.4及6.5,于(25±1)℃条件下放置21 d后取样测定抗体效价、聚合物(二聚体、多聚体)及F(ab')_2含量,评估低pH孵放病毒灭活法对上述质量指标的影响;以1 mL/瓶的规格分装经低pH孵放病毒灭活处理的马破伤风免疫球蛋白F(ab')_2,于(25±1)℃条件下存放6个月,定期取样并进行抗体效价、聚合物(二聚体、多聚体)及F(ab')_2含量检测,评估其稳定性。结果马破伤风免疫球蛋白F(ab')_2经低pH孵放病毒灭活后,其抗体效价、聚合物(二聚体、多聚体)及F(ab')_2含量未发生明显变化;样品于(25±1)℃条件下存放6个月后,抗体效价和F(ab')_2含量均符合《中华人民共和国药典》2015版(三部)的要求。结论低pH孵放病毒灭活法适用于马破伤风免疫球蛋白F(ab')_2病毒的灭活。
Objective To investigate effect to quality of equine anti-tetanus immunoglobulin F(ab')_2 by low pH incubation.Methods The four equal amounts of equine anti-tetanus immunoglobulin F(ab')_2 were conducted by using different range for pH 3.8,4.1,4.4,and 6.5,respectively,after placement at(25±1) ℃ for 21 days,the samples were determined for potency test,polymers content(dimer,polymerizer) and F(ab')_2 content to estimate the influence of low pH incubation on main indexes of tested equine anti-tetanus immunoglobulin F(ab')_2.The tested samples were encapsulated at 1 mL per ampoule,after 6 months placement at(25±1) ℃,the sampling were performed periodically and detecting in evaluation of stability for the tested samples.Results It was no a significant difference in potency test,polymers content and F(ab')_2 content before and after treatment by the low pH incubation;after 6 months placement at(25±1) ℃,all tested indexes met the requirement of Chinese Pharmacopoeia(Volume Ш,2015 Edition).Conclusion The low pH incubation was suitable to the virus inactivation of equine anti-tetanus immunoglobulin F(ab')_2.
Objective To investigate effect to quality of equine anti-tetanus immunoglobulin F(ab')_2 by low pH incubation.Methods The four equal amounts of equine anti-tetanus immunoglobulin F(ab')_2 were conducted by using different range for pH 3.8,4.1,4.4,and 6.5,respectively,after placement at(25±1) ℃ for 21 days,the samples were determined for potency test,polymers content(dimer,polymerizer) and F(ab')_2 content to estimate the influence of low pH incubation on main indexes of tested equine anti-tetanus immunoglobulin F(ab')_2.The tested samples were encapsulated at 1 mL per ampoule,after 6 months placement at(25±1) ℃,the sampling were performed periodically and detecting in evaluation of stability for the tested samples.Results It was no a significant difference in potency test,polymers content and F(ab')_2 content before and after treatment by the low pH incubation;after 6 months placement at(25±1) ℃,all tested indexes met the requirement of Chinese Pharmacopoeia(Volume Ш,2015 Edition).Conclusion The low pH incubation was suitable to the virus inactivation of equine anti-tetanus immunoglobulin F(ab')_2.
引文
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[6]国家食品药品监督管理总局.生物制品稳定性研究技术指导原则[EB/OL].(2015-04-15)[2018-11-16].http://www.nmpa.gov.cn/WS04/CL2138/300006.html.
[7]ROBERTS P L,DUNKERLEY C,WALKER C.Virus reduction in an intravenous immunoglobulin by solvent/detergent treatment,ion-exchange chromatography and terminal low pH incubation[J].Biologicals,2012,40(5):345-352.
[8]DICHTELMLLER H O,FLECHSIG E,SANANES F,et al.Effective virus inactivation and removal by steps of Biotest Pharmaceuticals IGIV production process[J].Results Immunol,2012,2:19-24.
[2]Word Health Organization.WHO guidelines for the production control and regulation of snake antivenom immunoglobulins[R].Geneva:Word Health Organization,2010.
[3]国家食品药品监督管理局.药品注册管理办法(局令第28号)[S].2007:附件3.
[4]国家药典委员会.中华人民共和国药典(三部)[S].北京:中国医药科技出版社,2015:通则123.
[5]国家药典委员会.中华人民共和国药典(第一增补本)[S].北京:中国医药科技出版社,2015.
[6]国家食品药品监督管理总局.生物制品稳定性研究技术指导原则[EB/OL].(2015-04-15)[2018-11-16].http://www.nmpa.gov.cn/WS04/CL2138/300006.html.
[7]ROBERTS P L,DUNKERLEY C,WALKER C.Virus reduction in an intravenous immunoglobulin by solvent/detergent treatment,ion-exchange chromatography and terminal low pH incubation[J].Biologicals,2012,40(5):345-352.
[8]DICHTELMLLER H O,FLECHSIG E,SANANES F,et al.Effective virus inactivation and removal by steps of Biotest Pharmaceuticals IGIV production process[J].Results Immunol,2012,2:19-24.