Chromatographic separation of three monoclonal antibody variants using multicolumn countercurrent solvent gradient purification (MCSGP).
Multicolumn countercurrent solvent gradient purification (MCSGP) is a continuous chromatographic process developed in recent years (Aumann and Morbidelli, 2007a; Aumann et al., 2007) that is particularly suited for applications in the field of bioseparations. Like batch chromatography, MCSGP is suitable for three-fraction chromatographic separations and able to perform solvent gradients but it is superior in terms of solvent consumption, yield, purity, and productivity due to the countercurrent movement of the liquid and the solid phases. In this work, the MCSGP process is applied to the separation of three monoclonal antibody variants on a conventional preparative cation exchange resin. The experimental process performance was compared to simulations based on a lumped kinetic model. Yield and purity values of the target variant of 93%, respectively were obtained experimentally. The batch reference process was clearly outperformed by the MCSGP process.
Müller-Späth
Thomas
T
Department of Chemistry and Applied Biosciences, ETH Zurich, Institute for Chemical and Bioengineering, Wolfgang-Pauli-Str. 10/HCI F 129, 8093 Zurich, Switzerland.
Aumann
Lars
L
Melter
Lena
L
Ströhlein
Guido
G
Morbidelli
Massimo
M
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000737:chemistry / Q000648:ultrastructure; D002852:Chromatography, Ion Exchange; D003377:Countercurrent Distribution; D031521:Fractionation, Field Flow; D007135:Immunoglobulin Variable Region / Q000648:ultrastructure; D007700:Kinetics; D008239:Lysine / Q000032:analysis / Q000235:genetics; D008956:Models, Chemical; D012212:Rheology; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D012997:Solvents; D008239:Lysine