Combined Yamamoto approach for simultaneous estimation of adsorption isotherm and kinetic parameters in ion-exchange chromatography.

摘要: Application of model-based design is appealing to support the development protein chromatography in biopharmaceutical industry. However, required efforts for parameter estimation are frequently perceived as time-consuming and expensive. In order speed-up this work, a new approach modelling ion-exchange linear conditions was developed. It aims at reducing time demand model calibration. The method combines kinetic thermodynamic parameters based on simultaneous variation gradient slope residence set five elutions. estimated from Yamamoto plot gradient-adjusted Van Deemter plot. combined increases information extracted per experiment compared individual methods. As proof concept, successfully applied monoclonal antibody cation-exchanger Fc-fusion an anion-exchange resin. estimations mAb confirmed that maintained accuracy usual plots. second case, offline size-exclusion performed estimate impurity (high molecular weight species) simultaneously with main product. Finally, obtained were used lumped simulate runs. simulated chromatograms wide range lengths times showed only small deviations experimental data.