(358b) Innovative Chromatographic Processes for Protein Purification

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


Various 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, together with the high purity and yield required, makes the purification process using current technologies a significant part of the total production cost of these materials.

Chromatography is often one of the key and most expensive steps of the purification process. Through a clear understanding of the fundamental equilibrium and transport processes involved in the chromatographic separation of biomolecules, quantitative models can be derived which can guide to the optimization of current processes and the development of innovative ones which provide a breakthrough in this field.

This refers in particular to the development of optimized modifier gradient profiles in traditional batch column operations and of 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, where the traditional protein-A based stationary phases have not been used.

A 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.