Single‐Use Bioreactors for Continuous Bioprocessing: Challenges and Outlook

The biopharmaceutical industry has widely accepted single-use technology in general and single-use bioreactors particularly. Mostly, single-use bioreactors are applied in (GMP) production, process development and at research level. By introducing continuous processing, due to the potentially higher volumetric productivity, the operational scale can decrease a factor 5-10. When the scale of operation is decreased with a factor 10 and the upstream part of the process is fully disposable, the direct, equipment related investment costs will be decreased by a factor 5-10. Although the maximum production scale can be considerably reduced when applying continuous processing, a thorough scale-up procedure is needed to scale a process from the laboratory scale to the final production scale. In order to seed a larger scale bioreactor (100 l and above), many steps have to be performed to generate sufficient viable cell material for inoculation. Usually, seeding is done in mammalian cell culture at starting densities of 0.2–0.5 × 106 cells/ml.