Mechanistic modeling for cation exchange chromatography process of trastuzumab and its application
10.16438/j.0513-4870.2023-1042
- VernacularTitle:曲妥珠单抗阳离子交换色谱过程机理模型建立及其应用
- Author:
Le-yi LI
1
;
Xu YAN
2
;
Jing-yu JIAO
3
;
Dan GAO
3
;
Dong GAO
3
;
Hai-bin QU
1
Author Information
1. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
2. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hisun Biopharmaceutical Co., Ltd., Hangzhou 311404, China
3. Hisun Biopharmaceutical Co., Ltd., Hangzhou 311404, China
- Publication Type:Research Article
- Keywords:
monoclonal antibody;
trastuzumab;
charge variant;
purification;
mechanistic modeling
- From:
Acta Pharmaceutica Sinica
2024;59(5):1391-1398
- CountryChina
- Language:Chinese
-
Abstract:
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.
