Genomic DNA causes membrane fouling during sterile filtration of cell lysates

[Display omitted] •Fast filter blocking of cell lysates on sterile filter due to genomic dsDNA.•Genomic dsDNA forms complex with positively charged molecules/proteins.•Heterogeneous complex can be dissolved by increasing ionic strength.•Endonuclease treatment enhances filter capacity due to dsDNA fragmentation.•Filter blocking phenomenon observed for different host cell/POI combinations. During biopharmaceutical production, efficient removal of impurities via filtration is essential. It is desirable to achieve high filter capacities along with a high degree of clearance. However, the complexity of bacterial cell lysates makes it difficult to properly estimate the filtration behavior. Here we investigated how host cell-derived impurities impacted the performance of commercially available sterile filters, with a focus on characterizing the dsDNA-induced decrease of filter capacity. Pressure flow curves at a constant flow, combined with particle analytics (e.g., nanoparticle-tracking analysis), indirectly revealed that dsDNA had a major influence on rapid membrane fouling. The observed phenomenon was more pronounced when using filters with small pore sizes (