Model‐based optimization of an ion exchange chromatography process for the separation of von Willebrand factor fragments and human serum albumin

Abstract Column liquid chromatography plays a vital role in the downstream processing of biopharmaceuticals, where the goal is to extract and purify a target protein from a mixture. In this work, we examine a real‐world ion exchange chromatography process where electrostatic interactions between proteins and the chromatographic medium are the predominant forces being exploited for the separation of the participating species. More specifically, we successfully separate a recombinant dimeric fragment of the von Willebrand factor, used for the half‐life prolongation of certain proteins, from human serum albumin. Compared to the originally conducted experiments, the optimized experiment achieves a higher product purity in less time and with lower consumption of buffer salts, hence being favorable both in economical and ecological terms.