Use of higher product concentrations in process intermediate streams offers opportunities to intensify downstream processes and facilitate adoption of more continuous approaches to biomanufacturing. However, there is limited fundamental understanding of how increased concentrations may affect parvovirus-retentive filtration, even though this step has a significant effect on manufacturing costs.<br/><br/>In this work, experimental studies were conducted to characterize the performance of adsorptive membrane prefilters commonly used to enhance virus filter capacity for a range of concentrations. In addition to varying the total protein concentration, the concentration of large product aggregates was varied independently. These large aggregates are typically responsible for fouling of virus filters and limit their capacity, and their adsorption was compared to common adsorption isotherms. The effects of protein and aggregate concentrations on the virus filter permeability and capacity were studied separately to quantify the contributions of solution viscosity, particulate fouling, and other phenomena.<br/><br/>These results were coupled with filter sizing studies under various flux conditions specific to continuous processing requirements and with optimization of the feed pH and conductivity to demonstrate a set of strategies to minimize filter area requirements and replacement frequency.

Effect of product concentration on continuous parvovirus-retentive filtration

253rd National Meeting (2017)

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