To manufacture products using multiple strains of anaerobic bacteria in the same production space and reactors, it is essential to use single-use systems from inoculation through final fill and finish. This is because anaerobic strains are typically challenging to cultivate and challenging to demonstrate sterility of shared bioprocessing surfaces between cultures. With stainless steel systems, changing from strain to strain is a time-consuming process that requires extensive cleaning followed by media sterilization, cultivation, and downstream processing. If a quality validation test shows the system does not pass, the batch is discarded, and cleaning must be repeated. Even with all these precautions, there is a chance a spore will survive the process and cause failure of the subsequent batch. Implementation of single-use systems is essential for a CDMO to obtain products from multiple anaerobic bacterial strains.
In collaboration with Arranta Bio, we cultured strict anaerobic bacterial strains in a 50 L Thermo Scientific™ HyPerforma™ Single-Use Bioreactor (S.U.B.). We then scaled up three similar oxygen-sensitive processes in a 250 L HyPerforma S.U.B. and scaled up again with a single strain in the 5,000 L Thermo Scientific™ DynaDrive™ Single-Use Bioreactor (S.U.B.). Because the Thermo Scientific™ HyPerforma™ Single-Use Fermentor (S.U.F.) and the subsequently enhanced S.U.F. are designed for aerobic cultures, we propose using S.U.B.s for anaerobic cultures. Our S.U.B.s have been shown to be gentler and less demanding for mammalian cell culture with homogenous mixing at high rates and best-in-class, durable films with a gas-impermeable design. Our S.U.B.s have smaller inlet and outlet filter lines and lower gassing rates, which is optimal for anaerobic bacterial cultures with the added advantage of proven scalability up to 5,000 L.