Abstract Monoclonal antibodies (mAbs) are one of the most important class of therapeutic proteins. Their proteinaceous nature makes them labile towards aggregation, considered a critical quality attribute (CQA) as it affects safety and efficacy of a biotherapeutic product. Present study examines early stage aggregation behaviour of monoclonal antibodies experimentally. The process is also described using hybrid reaction and population balance model. Size exclusion chromatography and dynamic light scattering have been used to obtain kinetic parameters featuring in the mechanistic model. The aggregation process of two different mAbs in the presence of either acetate or citrate buffer is analysed at two temperatures. The rate of aggregation is found to be significantly influenced by the type of buffer medium (faster in citrate compared to acetate buffer). The enhanced aggregation in citrate buffer is attributed to the reduction in the net energy barrier for protein-protein interaction resulting in loss of stability of mAb species.

中文翻译：

---

基于单克隆抗体的治疗蛋白聚集的群体平衡建模

摘要 单克隆抗体 (mAb) 是最重要的一类治疗性蛋白质。它们的蛋白质性质使它们容易聚集，被认为是关键质量属性 (CQA)，因为它会影响生物治疗产品的安全性和有效性。本研究通过实验检查单克隆抗体的早期聚集行为。还使用混合反应和种群平衡模型描述了该过程。尺寸排阻色谱和动态光散射已被用于获得机械模型中的动力学参数。在两个温度下分析了在醋酸盐或柠檬酸盐缓冲液存在下两种不同 mAb 的聚集过程。发现聚集速率受缓冲介质类型的显着影响（与醋酸盐缓冲液相比，柠檬酸盐更快）。柠檬酸盐缓冲液中增强的聚集归因于蛋白质-蛋白质相互作用的净能垒降低，从而导致 mAb 物种的稳定性丧失。