Nanying Bian discusses: “Considerations in selection of Protein A resin for efficient MAb capture”
As bioreactor titers increase, so does the pressure on downstream steps to effectively process the upstream feed. At the same time, downstream steps must become more cost effective. Given this challenging environment, selection of the optimum protein A resin for initial capture and purification of monoclonal antibodies is critical.
The first criterion by which protein A resins are evaluated is typically productivity, which quantifies the amount of Mab that can be processed in a given period of time per unit resin volume. Productivity calculations are based on many factors including feed titer, binding capacity, re-use cycles, and flow rate. A focus on productivity is especially important for manufacturers who need to process a quantity of material very quickly. A recent article by two of my colleagues describes the use of models to aid in developing a higher capacity protein A resin by assisting in selection of resin characteristics (Increasing MAb capture productivity. BioProcess International, May 2009 pp 56-61). The models also help to determine optimum operating conditions to maximize productivity and reduce manufacturing costs.
In addition to assessing productivity and overall process costs, one should look at product purity of the protein A elution pool prior to the cation exchange step. Purity is impacted by several factors including the initial feed composition and the intermediate wash steps.
Another consideration is resin cleaning protocols after each cycle. Some resins can be cleaned with alkaline protocols while others can be cleaned via well-established acid cleaning protocols. Additionally, effective sanitization between campaigns (3-5 cycles) are instrumental to extending number of re-use of Protein A resins. A 2009 article in the Journal of Chromatography described the development of a sanitization solution for silica-based protein A resins (Vol 1216, pages 4589-4596).
The protein A capture step is also one of the several orthogonal methods for viral clearance in the MAb purification process. As such, the virus clearance capabilities of various protein A resins also differ and should be considered when selecting a resin.
With so many protein A resin options available, a number of factors must be evaluated and weighed prior to selection. These include binding capacity, flow properties, product purity, sanitization, re-use, and virus clearance.