(389f) Economics and Process Monitoring of Continuous Processing for Multiple Viral Products

Rapid and cost-effective vaccine production has life-saving potential, as evidenced by the COVID-19 pandemic. Continuous processing promises increased flexibility and productivity compared to traditional batch chromatography-based processes. While continuous processing is increasingly common for protein therapeutics, adoption of continuous processing for viral products is lagging.

Aqueous two-phase systems (ATPS) combine product capture and purification by partitioning the viral product and contaminating host-cell proteins and DNA to different phases. Our process consists of two stages: the first ATPS stage separates the bulk of the viral product from the bulk of the impurities, while the second stage recovers the viral product from the viscous polymer phase to ease further processing. ATPS relies on biocompatible and environmentally-friendly raw materials rather than expensive proprietary consumables such as chromatography resin, which translates into over 50% lower production costs compared to traditional processes above a 11 kg production scale.

We have previously shown that porcine parvovirus (PPV), a non-enveloped vaccine model, can have a 66% recovery with over 90% removal of protein impurities and 94% host cell DNA after our two-stage process in batch mode. Batch performance has been compared to continuous processing, and in-process monitoring has been implemented for key performance drivers such as mixing and settling. A single-pass tangential flow filter has been constructed to continuously formulate the viral product after purification by ATPS. Furthermore, the purification framework has been tested for versatility by purifying an enveloped virus-like particle and adeno-associated viral product. This proof-of-concept study demonstrates that a two-stage aqueous two-phase system could be incorporated into a fully-continuous purification process that will make viral manufacturing both more flexible and cost-effective.