Cation Exchange Chromatography (CEX) is well-established and commonly used to remove aggregates in the manufacture of monoclonal antibodies. CEX can be operated in two different modes: Bind/Elute (B/E) and Flow-Through (FT).  Compared to conventional B/E mode, FT CEX confer advantages in large-scale manufacturing, including substantial process efficiency gains and resulting operational cost reduction, as well as process intensification for application within a semi-continuous chromatography platform.<br/>In this work, a generalized process development approach for FT CEX step design and optimization will be presented. Firstly, a commercially-available CEX resin with low ligand density was identified and initial frontal chromatography experiments were conducted to identify flow-through operating conditions and ranges using an IgG1 protein as a model system. More specifically, univariate breakthrough studies were performed to fully characterize aggregate selectivity. Secondly, an IgG4 protein that had exhibited severe on-column aggregation behaviour when processed in B/E mode was selected and evaluated following a similar methodology. In this case, on-column aggregation was fully avoided in flow-through mode, while achieving an increase in overall efficiency and selectivity for aggregate removal. Finally, leveraging the experimental data, the value provided by <i>in silico </i>mechanistic modeling as a predictive tool in cation-exchange process development in flow-through mode will be discussed.

Development of flow through cation exchange chromatography (FT CEX) to improve process efficiency and address on-column aggregation

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.