title: Prediction of reversible IgG1 aggregation occurring in a size exclusion chromatography column is enabled through a model based approach.
abstract: One important aspect of antibody separation being studied today is aggregation, as this not only leads to a loss in yield, but aggregates can also be hazardous if injected into the body. The aim of this study was to determine whether the methodology applied in the previous study could be used to predict the aggregation of a different batch of IgG1, and to model the aggregation occurring in a SEC column. Aggregation was found to be reversible. The equilibrium parameter was found to be 272 M(-1) and the reaction kinetic parameter 1.33 × 10(-5) s(-1) , both within the 95% confidence interval of the results obtained in the previous work. The effective diffusivities were estimated to be 1.45 × 10(-13) and 1.90 10(-14) m(2) /s for the monomers and dimers, respectively. Good agreement was found between the new model and the chromatograms obtained in the SEC experiments. The model was also able to predict the decrease of dimers due to the dilution and separation in the SEC column during long retention times.
authors.affiliation: Department of Chemical Engineering, Lund University, Lund, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Ojala
authors.affiliation: Department of Chemical Engineering, Lund University, Lund, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Sellberg
authors.affiliation: Novo Nordisk A/S, Gentofte, Denmark.
authors.forename: Thomas Budde
authors.initials: TB
authors.lastname: Hansen
authors.affiliation: Novo Nordisk A/S, Gentofte, Denmark.
authors.forename: Ernst Broberg
authors.initials: EB
authors.lastname: Hansen
authors.affiliation: Department of Chemical Engineering, Lund University, Lund, Sweden. bernt.nilsson@chemeng.lth.se.
authors.forename: Bernt
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D002138:Calibration; D002850:Chromatography, Gel; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008962:Models, Theoretical
chemical_list: D007074:Immunoglobulin G
keywords: Downstream processing; Modeling; Protein aggregation antibodies; Size exclusion chromatography