Fluid Phase Equilibria, Vol.261, No.1-2, 133-139, 2007
Development, modelling, optimisation and scale-up of chromatographic purification of a therapeutic protein
Development of a chromatographic purification step proceeds through a number of stages. High-throughput screening techniques are used to identify suitable resins. This technique is also suitable for the design of a capture step and some intermediate chromatographic steps, but development and true optimisation of a purification step necessitate simulations and thus models of the adsorption isotherm. A model for ion-exchange is reviewed and the strategy for estimation of model parameters is reported. Examples are shown where computer simulations are used for development and optimisation of chromatographic separations. Application of simulation of chromatographic processes supports innovation, efficiency and thus quality by design in biopharmaceutical development, manufacturing, and quality assurance and it enhances process understanding to facilitate innovation and risk-based regulatory decisions by industry. The theory of residence time based scale-up is developed and applied. (c) 2007 Elsevier B.V. All rights reserved.
Keywords:protein purification;resin screening;adsorption isotherms;computer simulation;scale-up;preparative chromatography;PAT;quality by design