Enabling high purities and yields in therapeutic peptide purification using multicolumn countercurrent solvent gradient purification

A therapeutic peptide was purified using multicolumn countercurrent solvent gradient purification (MCSGP) chromatography and its performance was compared to the performance of an optimized batch process in terms of yield, purity, productivity and solvent consumption. MCSGP simultaneously achieved high yield and purity while batch chromatography had to trade-off between these performance parameters. Using a single step preparative batch chromatography, product with a purity exceeding 97.0% could only be obtained with a yield lower than approximately 75%. For a final purity of 98.7% MCSGP showed a four-fold yield improvement (19% to 94%), a 10-fold increase in productivity (from 3 g/L/h to 30 g/L/h) and a decrease of the solvent consumption by 70% (from 3.5 L/g to 1.0 L/g). The results also showed the importance of gradient selection to obtain MCSGP parameters delivering a constant impurity profile from cycle-to-cycle.