Selection of Clarification Methods for Improved Downstream Performance and Economics

by Sarah Le Merdy
Volume 14, Issue 3 (Fall 2015)

The production of biopharmaceutical drugs typically involves a biological expression within a bacterial, yeast, or mammalian cell expansion system. Getting to the final product requires multiple purification steps, from primary clarification to the final formulation and sterile filtration. The aim of the initial purification steps is not to purify the stream perfectly but rather, to prepare the stream for finer and more specific purification steps further downstream. Apart from efficiently removing contaminants, the clarification stages also need to maintain high product recovery whilst being consistent and robust. The finer downstream purification stages represent the largest portion of production costs; and for monoclonal antibodies (MAb), they can represent up to 80% of the overall cost. This cost is, however, heavily impacted by the quality of the feed stream that has been produced. Early clarification and purification steps, although seemingly crude, are critical in removing contaminants and maintaining a cost-effective process further downstream. Selecting them scientifically, based on chosen performance markers, could thus improve the performances of downstream operations. After reviewing the typical feed stream compositions, this article reviews the existing literature and shows the advantages of thoroughly investigating and then selecting a clarification method that provides the best downstream performance and economics...

Le Merdy S. Selection of clarification methods for improved downstream performance and economics. BioProcess J, 2015; 14(3): 50–5.

Posted online October 9, 2015.