By Ben Madsen, Mark Smith, and Nephi Jones
S.U.B.s have emerged as a tool-of-choice in many PD and Pilot spaces and are now transitioning into certain commercial manufacturing spaces. Simultaneously, upstream bioprocesses have intensified to considerable benefit in increased titer and decreasing production-vessel size. As upstream cultures continue to intensify, these processes are beginning to strain the performance envelope of single-use bioreactors designed for less demanding cultures of yesteryear. We describe simple yet effective enhancements that enable Thermo Scientific HyPerforma S.U.B.s to meet the mass-transfer and mixing needs of intensifying processes at 50-500 L scale, while leveraging the hardware of existing systems. We also introduce a next generation of single-use bioreactor – DynaDrive S.U.B. – that exceeds upstream process needs in a novel framework that was developed with a keen eye toward robust operations, exceptional ease-of-use, future flexibility, and unprecedented mass transfer and mixing scale-up predictability up to 5,000 L working volumes.