Continuous Countercurrent Tangential Chromatography for Monoclonal Antibody Purification

Recent increases in antibody titers have generated renewed interest in lower-cost continuous chromatographic processes for antibody purification. The objective of this study was to design, build, and test a continuous countercurrent tangential chromatography system in which the resin (in the form of a slurry) flows sequentially through a series of static mixers and hollow fiber membrane modules to accomplish the binding, washing, elution, stripping, and equilibration steps in continuous operation with true countercurrent staging. Experimental studies were performed for the purification of an IgG4 monoclonal antibody from a model feed containing bovine serum albumin and myoglobin using a protein A affinity resin. Batch uptake / desorption experiments were used in combination with critical flux filtration data to design the continuous countercurrent tangential chromatography system. The process was stable during continuous operation, providing the IgG4 at 94% yield with greater than 97% purity. The antibody productivity was more than 40 g protein per liter of resin per hour, which is significantly greater than can be obtained using conventional packed columns. The results clearly demonstrate the potential of using continuous countercurrent tangential chromatography for large-scale antibody purification.