The Future Of Bioprocessing Through Process Compression And Intensification

By David Chau, 3M Biopharmaceutical Purification

When recombinant therapeutics first became popular in the early 1980s with the mass production of insulin, titers of around 0.2 grams per liter (g/L) and packed cell volumes (PCVs) around 0.1% were most common. However, recent advancements in cell line development and cell biology have now enabled PCVs of almost 10%, correlating to titers up to 5 or 10 and, in some cases, even 15 g/L. While these advancements have led to increased amounts of product being generated, they have also created obstacles related to harvesting. 

With higher cell densities and titers come higher contaminant levels, as well as more cluttered debris fields that must be purified in order to obtain the manufacturer’s product of interest (PoI). As upstream technologies continue to improve, new and innovative purification solutions are required to overcome these higher levels of contaminants and impurities.
Rather than the traditional approach of relying on contaminant size to carry out clarification, 3M decided to focus on exploiting the charge characteristics of different impurities and species in the cell culture. When all the contaminants in a cell culture are plotted based on their isoelectric point (i.e., at which a molecule is electrically neutral), much of what must be removed — cells, cell debris, DNA, chromatin, or viruses — is negatively charged relative to the harvest pH. The PoI, meanwhile, is positively charged.

The 3M Harvest RC Chromatographic Clarifier provides a single-stage harvesting step for high cell density clarification, rather than multiple-stage/multiple-unit operations, resulting in a 3-to-1 reduction in unit operations. Using charge to clarify materials, 3M was able to show higher product recovery, very predictable scalability at the bench or at manufacturing scale, and consistent effluent quality.