Purification of a Viral Protein by Ion-Exchange Chromatography: Methodology for Mechanistic Modeling and Comparison with a Statistical Approach
Publication in BioProcess International
David Pfister (Ypso-Facto), Lucrèce Nicoud (Ypso-Facto), Julie Vignon (Enovalife), Eric Forma (Sanofi)
We developed a mechanistic model to simulate purification of a viral-protein complex by cation-exchange chromatography on the “wrong side” of the molecule’s isoelectric point (in a pH range where the protein is mostly negatively charged).
Determination of model parameters started with titration experiments and tracer injections, then moved to linear gradient elutions and representative purification experiments.
The model was applied to quantify the influence of buffer-solution pH and salt concentration on yield and purity, and we compared those results with a statistical response surface obtained in a previous design-of-experiments study.
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We show how the mechanistic model reduces experimental effort while providing physically meaningful results, even outside of the domain studied experimentally.
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