%N 7
%K Process systems modelling, Quality by design, Chromatography modelling, Hydrophobic interaction chromatography, Purification process development, Therapeutic protein
%J CHEMICAL ENGINEERING RESEARCH & DESIGN
%X The development and validation of a chromatography rate model for an industrial multicomponent chromatographicbioseparation is presented. The model is intended for use in a process scenario to allow specific variables critical toproduct quality to be studied. The chromatography provides impurity clearance whilst producing a complex productcomposed of six closely related variants of a dimer protein therapeutic (∼30 kDa), with their monomer subunits in aspecific ratio. Impurity removal is well understood, however, achieving the correct monomer subunit ratio can posea purification challenge. We utilise a stepwise approach to develop a model for studying the effect of feed materialvariability on product quality. Scale down experiments are completed to quickly generate data for estimating modelparameters, before an iterative procedure is employed where the industrial process is used to refine parameters ina sequential manner, until model predictions exhibit satisfactory agreement with experimental data. Final modelpredictions were in good agreement with experimental product quality (within 3%). The results demonstrate howgood understanding of an industrial process can help facilitate model development when an exhaustive descrip-tion is not required, despite considering a chromatographic bioseparation with crude feed material and challengingpurification objectives.
%O © 2013 The Authors. Published by Elsevier B.V. All rights reserved. This work is licensed under a Creative Commons Attribution 3.0 Unported License.
%D 2014
%T Modelling of industrial biopharmaceutical multicomponent chromatography
%P 1304 - 1314
%A EJ Close
%A JR Salm
%A DG Bracewell
%A E Sorensen
%V 92
%L discovery1443433