Computer aided process design of affinity membrane adsorbers
Special Symposium - EPIC-1: European Process Intensification Conference - 1
EPIC-1: Multifunctionality (MF-3)
Keywords: membrane chromatography, affinity separation, elution, monoclonal antibodies, protein A
Computer aided process design of affinity membrane adsorbers
P. van Beijeren(1), P. Kreis(1), M. Mutter(2), S. Sommerfeld(2), W. Bäcker(2) and A. Górak(1)
1) University of Dortmund, Emil-Figge-Str. 70, 44227 Dortmund, Germany,
Phone: +49-231-7553034, Peter.vanbeijeren@bci.uni-dortmund.de
2) Bayer Technology Services (BTS), Leverkusen, Germany
A typical downstream process for antibodies consists of three separation steps, in which affinity chromatography is the most costly and time-consuming one. An alternative to affinity chromatography are affinity membrane adsorbers. The separation principle of both technologies is the specific interactions of antibodies with immobilized ligands. Conventional affinity chromatography operates using a packed bed of beads, where productivity is limited due to intra-particle diffusion. In membrane adsorbers the mass transport is governed by convection through the membrane pores and the antibodies can bind directly with the immobilized ligands. Membrane adsorbers offer therefore a much faster rate of separation, but have the disadvantage of a lower capacity compared to conventional chromatography.
Until now the focus of research has been set on modelling and simulation of breakthrough curves without including washing and elution stages. Several models for the loading step have been proposed, as well as design heuristics. In order to perform an overall process analysis the contribution of all the different process steps (loading, washing and elution) is required. Therefore this work has focused on the development of a complete process model, which does not only take into account the different steps, but also considers buffer vessels, dead volumes and product fractionation. The capturing of human IgG with Sartobind Protein A modules has been used as a test system, where the values of kinetic constants, capacities and dead volumes have been obtained from experimental results.
The model is applied for the optimization of important process parameters, such as flow rate and elution cut off criteria. These parameters have a strong effect on overall process performance, characterized by productivity, process yield, concentration factor, buffer consumption and processing time. Relations between process parameters and the mentioned process performance characteristics are presented in a systematic way and allows for computer aided design of affinity membrane adsorbers. The applicability of the method is illustrated by a case study based on the experimental results obtained with IgG and protein A. Additionally the output of the detailed process model can be used as input for commercial simulation tools like SuperPro Designer® in which complete downstream processes can be designed.
Acknowledgements
This work has been performed as part of the “Advanced Interactive Materials by Design” (AIMs) project, supported by the Sixth Research Framework Programme of the European Union (NMP3-CT-2004-500160).
Presented Thursday 20, 15:20 to 15:40, in session EPIC-1: Multifunctionality (MF-3).
