Protection of biomanufacturing processes from virus contamination through upstream virus filtration of cell culture media.

ABSTRACT

Cell-based manufacturing processes have occasionally been exposed to adventitious viruses, leading to manufacturing interruptions and unstable supply situations. The rapid progress of advanced therapy medicinal products needs innovative approaches to avoid any unwelcome reminder of the universal presence of viruses. Here, we investigated upstream virus filtration as a clearance step for any product too complex for downstream interventions. Culture media virus filtration was investigated with respect to virus clearance capacities under extreme conditions such as high process feed loading (up to ~19,000 L/m²), long duration (up to 34 days), and multiple process interruptions (up to 21 h). The small nonenveloped Minute virus of mice was used as relevant target virus, and as worse-case challenge for the investigated virus filters with a stipulated pore-size of about 20 nm. Certain filters-especially of the newer second generation-were capable of effective virus clearance despite the harsh regimen they were subjected to. The biochemical parameters for un-spiked control runs showed the filters to have no measurable impact on the composition of the culture media. Based on these findings, this technology seems to be quite feasible for large volume premanufacturing process culture media preparations.