Platform Process for an Autonomous Production of Virus-like Particles

Virus-like particles (VLPs) are a promising platform as carriers for vaccination and general treatments against many pathogens. While there are long development timelines and challenges in the production of clinical-grade VLPs, this study introduces a platform process for the production and purification of those particles, aided by process analytical technology (PAT). Fed-batch cultivation and consecutive purification, including novel membrane technology and anion-exchange chromatography, showed robust process performance with design and control spaces defined in previous studies. A novel, stable HEK293F cell line generated using the highly efficient Sleeping Beauty transposon vector technology showed a 3.6-fold increase in productivity compared to a reference cell line established using PiggyBac vector components. The in situ microscope from SOPAT GmbH successfully predicted the viable cell density of a mammalian cell culture, which had been demonstrated for the first time with this type of ISM. Furthermore, Raman, FTIR, and DAD spectroscopies were able to predict the main metabolites and impurities when implemented in the upstream process. FTIR spectra also depicted changes in the buffer composition, therefore enabling robust process control for the prediction of the buffer exchange rate during diafiltration. The applied PAT strategy can deliver real-time data, which is crucial when predictive control is realized with a digital twin. Combined with a robust platform process, the stated control strategy can pave the way toward the autonomous production of VLPs.