CHROM²--a method to enhance the dynamic binding capacity, yield and productivity of a chromatographic column

Therapeutic proteins are biotechnological products with a fast-growing market. Despite the rapid development of available process technologies, a bottleneck in production capacities is still present due to limitations in the associated downstream process, particularly within chromatographic purification steps. Membrane chromatography has been introduced as a promising alternative for conventional chromatography because it allows for higher throughputs but it does not deliver comparable dynamic binding capacities. To combine the strengths of the two technologies, the so-called "CHROM(2) concepts" are introduced, which merge conventional chromatography with membrane adsorption. The serial connection of a large conventional chromatographic column followed by a small membrane chromatography unit enables to combine the strength of both the individual technologies. The larger column delivers the required high binding capacity, whereas the rapid binding kinetics of membrane chromatography sharpens the breakthrough curve. Furthermore applied higher velocities do not result in poor breakthrough performance since the membrane chromatography is able to compensate for the poor column breakthrough performance. In comparison to column chromatography, the CHROM(2) setup exploits the full column capacity and delivers higher productivities and yields.