title: Modeling and robust pooling design of a preparative cation-exchange chromatography step for purification of monoclonal antibody monomer from aggregates.
abstract: This study has implemented and calibrated a model that describes the separation of the monomer of monoclonal antibodies from the dimer and larger oligomers on preparative-scale using cation-exchange chromatography. A general rate model with temperature dependent diffusion was coupled to a pH- and temperature-dependent steric mass action model. The model was shown to predict the retention of the monomer, dimer, and oligomer at low loadings for different pH levels and temperatures. Additionally, the model was shown to adequately predict the elution behavior of the monomer and soluble aggregates at high loadings within the same ranges with some limitations. The model was not able to accurately describe the shape of the product break-through curves or the slight levels of co-elution of the dimer and oligomer with the monomer at higher pH. The model was used to predict how 12 process variations impact the separation. The model is used to establish an elution end collection criterion such that the step can robustly provide the target purity of monomers.
authors.affiliation: Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Borg
authors.affiliation: Product and Process Development, Amgen, 1201 Amgen Court West, Seattle, WA 98119, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Brodsky
authors.affiliation: Product and Process Development, Amgen, 1201 Amgen Court West, Seattle, WA 98119, United States.
authors.forename: John
authors.initials: J
authors.lastname: Moscariello
authors.affiliation: Biosimilars, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors.forename: Suresh
authors.initials: S
authors.lastname: Vunnum
authors.affiliation: Product and Process Development, Amgen, 1201 Amgen Court West, Seattle, WA 98119, United States.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Vedantham
authors.affiliation: Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Westerberg
authors.affiliation: Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden. Electronic address: bernt.nilsson@chemeng.lth.se.
authors.forename: Bernt
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000302:isolation & purification*; D002411:Cation Exchange Resins / Q000737:chemistry*; D002852:Chromatography, Ion Exchange / Q000295:instrumentation / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008962:Models, Theoretical; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; D002411:Cation Exchange Resins
keywords: Adsorption isotherm; Aggregate removal; Chromatography modeling; Monoclonal antibodies; Process control; Product pooling