Scale-Up of Twin-Column Periodic Counter-Current Chromatography for MAb Purification
James Angelo, John Pagano, Thomas Müller-Späth, Kathleen Mihlbachler, Srinivas Chollangi, Xuankuo Xu, Sanchayita Ghose, and Zheng Jian Li
Periodic countercurrent (PCC) processes increasingly are being evaluated as alternatives to
single-column batch capture processes. Some of the advantages of PCC processes over single-column processes include shortening of processing time and/or reduction of required resin volume through increased productivity; reduction in resin costs through improved resin
capacity use; and reduction in buffer consumption through increased column loading. Those advantages, however, come with increased equipment complexity and hardware costs. PCC processes and systems with two to up 16 columns of the same type have been proposed. As the number of columns increases, a process becomes more complex, potentially adding pumps, detectors, valves, and plumbing. The PCC process investigated in this study was a CaptureSMB process: a PCC process using two columns and modulated feed flow rates. All PCC processes are
based on the concept of loading the first affinity column beyond its dynamic breakthrough capacity and capturing what breaks through in a second column of the same type. So the first column can be loaded to values of 50−80% breakthrough, whereas in batch chromatography,
loading is typically performed to values below 1% breakthrough to prevent product loss (1). Based on the adsorption kinetics and mass-transfer properties of commercially available
protein A resins, interconnecting more than two columns in the load zone provided little improvement in performance (2, 3).
Click on the image to the right to view this pre-print version of an article that will appear in the April 2018 issue of BioProcess International magazine.