Cation-exchange displacement chromatography for the purification of recombinant protein therapeutics from variants

Removal of low level impurities that are closely related to the bioproduct is a commonly encountered challenge in the purification of biopharmaceutica ls. These separations are typically carried out by using shallow linear sal t gradients at relatively low column loadings, significantly limiting the t hroughput of the purification process. In this manuscript we examine the ut ility of displacement chromatography for the purification of recombinant hu man brain-derived neurotrophic factor, rHuBDNF. The utility of displacement chromatography is compared to gradient elution for the removal of variants of the rHuBDNF. The results demonstrate that displacement chromatography i s capable of achieving high yields and purity at high column loadings. Disp lacements developed on 20 mu m and 50 mu m cation-exchange resins are shown to provide 8-fold and 4.5-fold increases in production rates, respectively , when compared to an existing linear gradient elution operation. These res ults demonstrate the efficacy of displacement chromatography for the purifi cation of therapeutic proteins from complex feed streams. (C) 1998 Publishe d by Elsevier Science B.V. All rights reserved.