Experimental and simulation analysis of membrane adsorbers used for the primary capture step in antibody manufacturing

The use of membrane adsorbers for polishing steps in protein therapeutics manufacture has evolved into a feasible choice for the biopharmaceutical industry. Conversely, membrane affinity chromatography for the primary capturing step is still far from being applied, due to the low binding capacity of affinity membranes with respect to chromatography beads. In this work, a new affinity membrane endowed with a very interesting binding capacity for human IgG is proposed for the capturing step of a monoclonal antibody production process. The membranes have been extensively tested with pure polyclonal IgG solutions and with a cell culture supernatant containing IgG1. The effects of flow rate and IgG concentration in the feed on the separation performances like binding capacity, selectivity and process yield have been studied in detail. A model simulation of the complete affinity cycle has been developed and the experimental results have been compared with the simulated behaviour for different values of feed concentrations and feed flow rates. The results show that i) these new affinity membranes, endowed with high binding capacity, can be used to overcome the throughput limitation and other well known drawbacks of traditional bead-based chromatographic columns, and ii) that the model developed satisfactorily describes the observed behaviour and can be used for process design and simulation.