细胞培养基成分对单抗原液颜色的影响  

The Effect of Cell Culture Medium Components on the Color of Monoclonal Antibody Substance

作　　者：王晓飞 王攀 刘晓静 徐胜楠 毛佳琪 林云飞 李国柱 秦国宏 WANG Xiaofei;WANG Pan;LIU Xiaojing;XU Shengnan;MAO Jiaqi;LIN Yunfei;LI Guozhu;QIN Guohong(Nanjing Chia-Tai Tianqing Pharmaceutical Co.,Ltd.,Fanghua Pharmaceutical Research Institute,Department of Biology,Nanjing 210046,China.)

机构地区：[1]南京正大天晴制药有限公司芳华药物研究院生物所,江苏南京210046

出　　处：《山东化工》2024年第20期132-134,138,共4页Shandong Chemical Industry

摘　　要：皮下注射生物治疗药物已经成为许多疾病领域静脉给药的有价值的替代方案,高药物浓度逐渐成为单克隆抗体(Monoclonal antibody,mAb)的标准。随着单抗原液(Drug Substance,DS)浓度的增加,原液可能比在低浓度下显示出更强烈的颜色,生物制药行业最近报道了除无色或淡黄色以外的非典型原液颜色。原液颜色作为生物制剂释放度、稳定性和可比性研究的重要质量指标,找到引起原液变色的根本原因并降低原液颜色是十分必要的;同时,这也有助于简化临床研究中安慰剂的设计过程。。相关研究表明,原液颜色是由培养基中一些特定成分造成的,总结了不同培养基成分对单抗原液颜色的影响。铁离子导致蛋白质中的色氨酸氧化形成甲酰基犬尿氨酸和犬尿氨酸产物,这可能是导致原液呈黄色的原因;原液呈粉红色是由与原液结合的残留维生素B12所致;棕色是黄色和粉色组合作用的结果。As Subcutaneous injection of biotherapeutic drugs has become a valuable alternative to intravenous administration in many disease areas,and high drug concentrations are increasingly becoming the norm for monoclonal antibodies.As concentrations of monoclonal antibody increase,drug substance may show a more intense color than at lower concentrations,and the biopharmaceutical industry has recently reported atypical drug substance colors other than colorless or yellowish.As an important quality index for the study of release,stability and comparability of biologics,it is necessary to identify the root cause of drug substance discoloration and reduce its color,which also simplifies the design process of placebos for clinical research.Relevant studies have shown that drug substance color is caused by some specific components in the medium.This paper summarizes the effects of different medium components on drug substance color of monoclonal antibody.Iron ions lead to the oxidation of tryptophan in protein to formylkynurenine and kynurenine products,which may be the reason for the yellow color of drug substance;The pink color of drug substance is caused by residual vitamin B 12 that binds to drug substance;Brown is a combination of yellow and pink.

关 键 词：抗体 原液颜色 细胞培养基 铁 维生素B12 

分 类 号：TQ460[化学工程—制药化工] Q819[生物学—生物工程]