摘要
目的采用微流成像颗粒分析技术(micro-flow imaging,MFI)测定在单克隆抗体注射液(简称单抗)中的不溶性微粒,探究不同工艺的单抗在不同储存条件下,不溶性微粒的粒径分布和硅油颗粒主要动态变化,提供更全面的微粒表征,为企业提升单抗药物稳定性和安全性提供参考。方法取企业A和B的单抗产品改变其储存条件,如开封后在4℃下静置、在常温下震荡,将其与不作处理的对照组分别用MFI检测其中的不溶性微粒,提取微粒的图像、粒径和计数等信息用于比较。结果比较开封4℃下静置和常温下振荡A和B企业单抗产品后的不溶性微粒总数和浓度,结果无统计学意义(P>0.05),4℃静置导致B企业单抗不溶性微粒的平均径粒大小分布变大,1.5~2.0μm(t=-4.26,P=0.02)的硅油粒子含量升高;振荡导致B单抗不溶性微粒≤1μm(t=5.45,P<0.001)的粒子明显减少,1~10μm(t=-5.43,P<0.001)之间的微粒增加,以及硅油含量升高,说明不同企业的单抗对于不同储存条件的敏感度不同。结论本研究将MFI应用于单克隆抗体注射液不溶性微粒的检测,为探讨生化蛋白药物的不溶性微粒来源提供新思路。相较于传统光阻法或显微镜计数,本研究首次将MFI技术深度应用于解析单抗制剂中蛋白质-硅油复合物的形成机制,为微粒来源的追溯提供了直接可视化证据。在储存条件改变的情况下,B企业单抗的不溶性微粒径粒分布和硅油含量变化较明显,提示该企业可优化产品、关注内包材的材料选择以提升产品的安全性和稳定性;结合图像推测平均径粒分布变大的部分原因是由于蛋白质-硅油复合物的形成,但硅油具体的产生原因仍需进一步探究。
OBJECTIVE To explore the particle size distribution and dynamic changes of silicone oil particles in monoclonal antibody injections(mAbs)manufactured by different processes and placed under various storage conditions using micro-flow imaging(MFI)technology,thus to provide a more comprehensive characterization of particles,offering valuable insights for pharmaceutical com-panies to enhance the stability and safety of monoclonal antibody drugs.METHODS mAbs from company A and company B were sub-jected to altered storage conditions:static storage at 4℃ post-opening and agitation at room temperature.These were compared with untreated controls using MFI to detect insoluble particles.Particle images,size distributions,and counts were analyzed.RESULTS MFI revealed no statistically significant changes in total insoluble particle count or concentration of mAbs from either compa-ny under static 4℃ or agitated conditions(P>0.05).However,static storage at 4℃increased the average particle size distribution(t=-4.26,P=0.02)and elevated silicone oil droplet content(1.5-2.Oμm)in company B's mAbs.Agitation reduced≤1μm par-ticles(t=5.45,P<0.001)but increased 1-10μm particles(t=-5.43,P<0.001)and silicone oil content in company B's mAbs,indicating varying sensitivities to storage conditions across manufacturers.CONCLUSION This study demonstrates the utility of MFI in detecting insoluble particles in mAbs and proposes new approaches for investigating their origins.Under altered storage conditions,com-pany B's mAbs exhibited notable shifts in particle size distribution and silicone oil content,suggesting a need for product optimization and material selection in primary packaging to enhance stability and safety.Image analysis suggests that increased particle size may stem from protein-silicone oil complex formation,though the exact mechanisms of silicone oil generation require further exploration.
作者
郑楠
温俊龙
王子豪
穆矛
ZHENG Nan;WEN Junlong;WANG Zihao;MU Mao(Guangdong Institute for Drug Control,Guangzhou 510663,China)
出处
《中国药学杂志》
北大核心
2025年第19期2071-2078,共8页
Chinese Pharmaceutical Journal
基金
广东省医学科学技术研究基金项目资助(A2024567)
广东省药品监督管理局科技创新项目资助(2024TDB01)。
