曲妥珠单抗阳离子交换色谱过程机理模型建立及其应用

Mechanistic modeling for cation exchange chromatography process of trastuzumab and its application

阳离子交换色谱作为一种常用的生物制药分离和纯化技术,常用于单抗的下游生产过程以分离电荷异质体。对于电荷异质体种类复杂、分离度低的样品,基于紫外数据的收集方式无法明确各异质体的组成,因此无法直接确定合并范围,仍需进行繁琐的馏分分析来指导产品收集。本文对目标单抗关键组分的阳离子交换色谱过程建立机理模型,并辅助于产品收集。该模型可以准确预测电荷异质体的洗脱峰形状,且真实值与预测值的均方根误差小于0.009。与基于在线紫外的收集方式相比,模型辅助收集方式不仅能够可视化洗脱过程,并且在保证产品合格率的情况下可提高相对产率4倍。

Cation exchange chromatography,as a commonly used separation and purification technique in biopharmaceutical manufacturing,is often employed for downstream processes to separate target monoclonal antibodies from their charge variants.For samples with complex and poorly resolved charge variant profiles,the collection solely based on ultraviolet detection does not provide specific compositional information for individual charge variants,making it challenging to determine the range of pooled fractions directly.Subsequent laborious fractionation analysis is then required to guide collection according to production requirements.A mechanistic model for the cation exchange chromatography process of the target monoclonal antibody's critical components was established,and it was employed to assist in product collection.The model accurately predicted the elution peak shapes of the modeled variants,with a root mean square error between predicted and actual values below 0.009.In comparison to the online ultraviolet-based collection method,the model-assisted collection method not only visualized the chromatographic process but also increased the relative productivity by fourfold while ensuring compliance rate.