The environmental impact of pharmaceutical R&D and production is considerable. Although the industry is rather conservative and also constrained by regulatory guidelines, there is increasing interest in the implementation of sustainable practices that not only improve corporate social responsibility (CSR) performance but also reduce costs and increase efficiency. This effort is embodied in the concept of Green Chemistry and includes reducing the use of toxic solvents in production and purification, which is a considerable problem. Solutions include recycling and the use of upstream protective columns that remove bioburden to increase the life-cycle of columns used downstream, or even make certain solvent-consuming steps redundant altogether.
Designing an optimized purification process means maximizing yield and purity, and at the same time controlling costs. So, you remove a lot of bulk impurities during the first steps, and focus on high yield steps at the end, when every gram is precious. If you’re purifying mAbs, it would also be good to remove impurities before affinity chromatography to protect the protein A column and reduce the need for cleaning in place (CIP).
The purity requirements for therapeutic peptides are very stringent, but synthesis generates a crude peptide mixture containing failed sequences and chemical variants, while recombinant peptides have a considerable bioburden from the host cell. These crude feeds can foul the reverse phase chromatography (RPC) columns commonly used in peptide purification. Introducing an orthogonal purification step upstream significantly reduces the burden on the expensive high performance RPC column, increases the peptide yield and purity, and also prolongs column lifetime.
What are the benefits of introducing multimodal ion exchange chromatography as a guard column and could they include a significant increase in mAb purity? This article presents a study in which two protein A affinity chromatography resins were compared to see whether the introduction of a guard column could improve mAb purity and to discover which of the protein A resins produced the best results.