Ion exchange chromatography (IEC) is a widely used unit operation in the purification of therapeutic proteins. However, the performance of an ion-exchange process depends on a complex interrelationship between several parameters, such as protein properties, mobile phase conditions, and chromatographic resin characteristics. Consequently, batch variations of IEC resins play a significant role in the robustness of these downstream processing steps. Ligand density is known to be one of the main lot-to-lot variations, affecting protein adsorption and separation performance. The use of a model-based approach can be an effective tool for comprehending the impact of parameter variations (e.g. ligand density) and their influence on the process.<br/>The objective of this work was to apply mechanistic modeling to gain a deeper understanding of the influence of ligand density variations in anion exchange chromatography. To achieve this, 13 prototype resins having the same support as the strong anion exchange resin Fractogel® EMD TMAE (M), yet only differing in ligand density, were analyzed. Linear salt gradient elution (LGE) experiments were performed to observe the elution behavior of BSA and a monoclonal antibody. An extended stoichiometric displacement model for ion-exchange chromatography, describing the dependence of ligand density variations on protein retention, was successfully applied. Additionally, a lumped rate model was used to perform in silico simulations, which proved the reliability of the model.

Mechanistic modeling of ligand density variations in anion exchange chromatography

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.