(287e) Continuous Chromatography for Protein Purification

Morbidelli, M., Institute of Chemical and Bioengineering, ETH Zurich

Various different proteins are finding highly valuable applications in various industrial areas, as demonstrated for example by monoclonal antibodies for therapeutic applications. In many cases these proteins are needed in significant amounts but are produced through fermentation processes which lead to supernatant concentrations which are at best in the order of a few grams of protein per litre. This makes the purification process a significant part of the total production cost of these materials. The current technologies, largely based on solvent-gradient batch chromatography, are clearly unsatisfactory since suffer from low recoveries, low productivities and high solvent requirements.

A significant breakthrough can be obtained by introducing innovative continuous processes able to integrate gradients of a suitable modifier. A prototype of such a process, referred to as Multi-column Counter-current Solvent-Gradient Purification (MCSGP), has been realized and its performance is discussed. Several industrial purification processes are considered, such as the purification of a growth hormone and a monoclonal antibody. In addition, the influence of important operating parameters of the MCSGP-unit, e.g. the switch time and the product flow rate, on the yield and the purity of the process has been investigated numerically as well as experimentally. The obtained results are explained using the analytical solution of a simplified model of the unit based on the classical equilibrium theory. A numerical comparison of the performance of the MCSGP-unit with that of the currently available technologies indicates significant improvements in terms of yield, productivity and solvent requirement.