Model-assisted process optimization of ion-exchange chromatography for monoclonal antibody charge variant separation

For the separation of monoclonal antibody charge heterogeneous species, an ion-exchange chromatography mechanism model is used to predict the elution and separation behavior and assist in the optimization of process conditions. The calibration experiments were designed to estimate the model parameters and the model simulation matched well with the experiments, demonstrating the model has good predictive ability. The model was used to compare and evaluate the influences of different elution modes and conditions. The optimal two-step elution was obtained to achieve high yield. However, it was found that the separation efficiency was highly sensitive to the salt concentration of first-step elution solution. Therefore, the process robustness was considered further to optimize the salt concentration, and it was found the salt concentration of 108.5 mmol/L could greatly enhance the process robustness. The results of validation experiments showed that the highest yield of two-step elution process reached 85.3%, and the operating range of the salt concentration of first-step elution was widened to 98.9—117.5 mmol/L. The results demonstrated that model-assisted process optimization could facilitate the complex condition analysis, promote the optimization and provide reasonable solutions for process robustness. © 2024 Materials China. All rights reserved.