<br/>Model-based process development of ion-exchange chromatography has become increasingly important in recent years. Efficient modeling of these processes requires knowledge of the full adsorption isotherm that describes how resin properties, buffer conditions, and other process parameters affect the adsorption equilibrium.<br/>Commonly, the mathematical description of the isotherm is based on the stoichiometric displacement model or its successor, the steric mass action model. These isotherms have been first considered for modeling the influence of salt concentration on the adsorption equilibrium and were later extended to quantitatively describe additional effects like buffer pH. Due to the abstract nature of stoichiometric models, model extensions are usually performed on an empirical bases and are often associated with a significant increase in model complexity, resulting in challenges for model calibration. They also do not explicitly consider resin or protein properties. Thus, parameter values can only be used for a distinct protein-resin combination.<br/>In the presented work, we discuss alternative non-stoichiometric protein adsorption models that are based on a colloidal representation of proteins. Multiple models have been proposed in the past, which differ in model complexity and model assumptions. We present a model that results from a detailed examination of these assumptions. It provides deeper mechanistic insights how resin properties, protein properties, and buffer conditions affect protein adsorption. The model complexity is limited to a small number of physically meaningful model parameters which enables rapid parameter estimation and supports the use of homology models in model calibration. The benefit and industrial applicability of the model is demonstrated by describing the separation of an industrial monoclonal antibody in a cation exchange purification step.

Modeling of ion-exchange chromatography: Are we making the right assumptions?

2019 Spring National Meeting

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