Development of a step‐gradient simulated moving bed process for the polishing of monoclonal antibodies with anion exchange chromatography

Abstract BACKGROUND In recent years, biopharmaceutical applications in medicine have seen explosive growth and the need for efficient, rapid and inexpensive purification of these targets is the topic of tremendous research and development. The need to improve process efficiency has been an active area of investigation due to the tremendous potential for these targets. The aim of the presented study is to transfer a flowthrough monoclonal antibody polishing process, utilizing anion exchange chromatography, to a step‐gradient simulated moving bed (SMB) method. Recently published research on step‐gradient SMB has focused almost exclusively on the model‐based development of purification processes; meanwhile, this work shows a successful empirical approach. RESULTS The flowthrough batch polishing process and the flowrate balances of an open‐loop SMB were used as the experimental basis for the initial SMB process designs, while optimization was performed empirically using a design of experiments approach. The developed process was then compared to the classical flowthrough batch process and an intensified batch process. Furthermore, a post‐load wash step was developed to increase the product recovery of the step‐gradient SMB method. CONCLUSION When compared to a standard batch purification process, the step‐gradient SMB process developed in this study resulted in a productivity increase of up to 90% while reducing buffer consumption by 75%, with purity levels of 99% to 100%, comparable to the batch process. © 2025 Tosoh Bioscience GmbH. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).