The optimal flow rate and column length for maximum production rate of protein A affinity chromatography

Abstract

Production rate is an important parameter in the design of efficient protein A affinity chromatography processes for purifying recombinant monoclonal antibodies. A simple equation was derived that expresses production rate in terms of flow rate and column length. Changes in flow rate and column length will not affect the antibody and are therefore easily varied for bioprocess applications. In the equation, production rate depends on dynamic capacity, which can be expressed as a function of the load flow rate and column length. The only empirical data needed for production rate optimization is the relationship of dynamic capacity to load flow rate and column length, which was quickly determined by using an on-line assay. The optimal production rate was found at a high flow rate, a low column length, and a low dynamic capacity, which has several implications for using high production rate protein A affinity chromatography for antibody manufacturing.