Continuous Virus Filtration: Solutions for Virus Challenge Testing and Production Sterility

‌Advances in enabling technology such as multi-column chromatography and single pass tangential flow filtration have empowered the production of monoclonal antibody (mAb) products and other biologics through continuous processing and process intensification.  This has led to the increase in scenarios where adjacent unit operations need to operate at lower process flowrates for greatly extended processing times.
 
Two major practical difficulties arise out of this new design space of extended processing time for virus filtration: simple sterility assurance, and the ability to generate effective virus challenge data over long periods of time.  Both are increased in complexity by the use of adsorptive prefiltration and virus filtration in the same system.
 
We demonstrate the effective performance of a gamma irradiated prefilter and virus filter pairing in one single use system for effective mAb processing and sterility assurance.  We also present three different approaches to generating virus challenge data with extended mAb processes and adsorptive prefilters: one spike, one study; spike replenishment; and in-line spiking.  All techniques can deliver stable and consistent input spikes over 4 days, with the latter two methods capable of being extended to any desired process time and a variety of virus and product stability scenarios.  Batch and continuous scenarios are compared with either 4 hour or 4 day processing of high mAb throughput (1600 L/m², 12 kg/m²) and > 6 log retention of minute virus of mice.