(147c) A Comparative Study of Protein a Membranes for the Rapid Purification of Monoclonal Antibodies

Chromatography is ubiquitous to therapeutic protein purification. When the protein is a monoclonal antibody (mAb), Protein A chromatography is used in the capture step to separate the product selectively from process impurities such as host cell proteins (HCPs), host cell DNA, viruses, charged variants, fragments, endotoxins and aggregates. Among the issues in resin-based Protein A chromatography is the low throughput associated with flowrate-dependent performance. In particular, diffusion limitations require resin columns to be operated with long residence times to achieve satisfactory binding capacities.

Protein A membrane chromatography is a solution. Recent innovations in Protein A membrane chromatography have led to products with binding capacities on par with resin chromatography using residence times that are shorter by an order of magnitude or more. The objectives of this study were to provide the first preliminary comparison of all commercial Protein A membranes in terms of performance metrics like dynamic binding capacity, equilibrium binding capacity, regeneration-reuse performance, HCP clearance, DNA clearance and elution peak volumes, and physical properties like pressure-flow rate dependence, pore size, surface area and dead volumes. The commercial Protein A membranes include Purilogics Purexa^TM-A, Gore® Protein Capture Device, Cytiva HiTrap^TM Fibro Prism A, and Sartorius Sartobind® A chromatography columns.

The results presented in the study represent a summary of the breakthrough in performance of Protein A membrane adsorbers in comparison to resins. In terms of binding capacity and impurity clearance, these membranes are ready to compete and, in certain cases, outperform resins. The performance metrics and physical properties presented show how Protein A membranes can fit into bioprocessing schemes, especially at small scales.