Advances in Membrane Chromatography for the Capture Step of Monoclonal Antibodies

Background: Monoclonal antibodies are nowadays by far the most important of all biotherapeutics. Unfortunately, they are complex proteins, so that their production is complicated and expensive, which eventually leads to an elevated average cost per treatment per patient. An important research effort is dedicated to the development of a process that may allow a reduction of antibodies production costs. Objective: In particular, the main target is to replace the capture step based on the very expensive use of protein A beads, which is, and has been, the standard for the last 20 years. Among the possible alternatives the use of membrane chromatography for antibody capture will be considered in this work. Despite the development of new convective stationary phases with improved binding capacity, the use of membrane adsorbers for capture chromatography is still limited to niche applications. Conventional packed bead columns are still preferred due to their higher binding capacity even if they suffer from several limitations such as high pressure drop, slow mass transfer through the diffusive pores and strong dependence of the binding capacity on flow rate. An overview of the recent work performed in the field and a critical review of how technology advances could make a breakthrough will be presented here.