title: Modeling of complex antibody elution behavior under high protein load densities in ion exchange chromatography using an asymmetric activity coefficient.
abstract: A main requirement for the implementation of model-based process development in industry is the capability of the model to predict high protein load densities. The frequently used steric mass action isotherm assumes a thermodynamically ideal system and, hence constant activity coefficients. In this manuscript, an industrial antibody purification problem under high load conditions is considered where this assumption does not hold. The high protein load densities, as commonly applied in industrial downstream processing, may lead to complex elution peak shapes. Using Mollerup's generalized ion-exchange isotherm (GIEX), the observed elution peak shapes could be modeled. To this end, the GIEX isotherm introduced two additional parameters to approximate the asymmetric activity coefficient. The effects of these two parameters on the curvature of the adsorption isotherm and the resulting chromatogram are investigated. It could be shown that they can be determined by inverse peak fitting and conform with the mechanistic demands of model-based process development.
authors.affiliation: GoSilico GmbH, Karlsruhe, Germany.|Karlsruhe Institute of Technology (KIT), Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe, Germany.
authors.forename: Thiemo C
authors.initials: TC
authors.lastname: Huuk
authors.affiliation: GoSilico GmbH, Karlsruhe, Germany.|Karlsruhe Institute of Technology (KIT), Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hahn
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Doninger
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Griesbach
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hepbildikler
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hubbuch
mesh_terms: D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D002852:Chromatography, Ion Exchange; D008962:Models, Theoretical; D008970:Molecular Weight; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D011506:Proteins
keywords: Activity coefficient; Downstream process development (DSP); Industrial application; Model-based process development (MBPD); Steric mass action isotherm (SMA)