Evaluation of Filterability of Cell Culture Media Components Using Virus Retentive Filters

Filtration of cell culture media is a critical step in bioprocessing to ensure the sterility of the media and prevent contamination of the bioreactor. While traditional processes employ sterile filtration to remove bacterial contaminants, there is a growing interest to implement a virus filter at this step in order to provide more comprehensive bioreactor protection. The pore size of a virus filter is an order of magnitude smaller than a sterile filter, which increases the risk of filter plugging, a major concern in upstream bioprocessing.

To better understand the impact of media components on virus filter fouling, a comprehensive study was undertaken to evaluate specific classes of components for their impact on filter capacity. Specifically, hydrophobic components, relatively large components, and components with relatively poor solubility were evaluated. We found that the greatest impact on filter capacity was from metal salts with poor solubility; hydrophobic and relatively large components had no measurable impact. We demonstrated that fouling could be mitigated by changing the iron source in our model media formulation. By understanding the source of fouling, it may be possible to adjust media formulations, making it more feasible to implement virus filtration and thereby reduce bioreactor contamination risk.