Improved feedstream titers are driving a demand for increased downstream processing productivity as manufacturers seek to lower the costs of monoclonal antibodies (MAbs). The unique selectivity of Protein A has enabled platform technologies for MAb purification. Platform technologies and chromatography resin improvements can help manufacturers achieve rapid and economical process development and scale-up. A multiprong approach can enable downstream process scientists to enhance productivity.
To solve these multiple demands, several solutions have been developed, including, among others, the use of platform technologies and chromatography resin improvements.
A downstream platform technology is based on experience with purifying a class of products with similar properties. With more than 500 MAbs currently in preclinical studies, monoclonal antibodies represent the greatest number of biotechnology products to which similar purification processes can be applied. In particular, the unique selectivity of Protein A has enabled the development of platform technologies for the purification of monoclonal antibodies.
Monoclonal antibodies usually differ from one another in surface charge and glycosylation. By selecting and adjusting unit operations, selectivity is achieved for each MAb. Typically, the order of anion and cation exchange steps might be reversed, hydrophobic interaction chromatography might replace cation exchange chromatography, or hydroxyapatite columns might be used. Before adding or substituting a chromatography step, it is usually advisable first to try optimizing the process by evaluating column load, wash and elution buffers, and pH. Of particular importance is pH, as some proteins tend to aggregate when exposed to low pH. Downstream platform technologies thereby simplify development across the breadth of MAb products.