Adoption of next-generation processing and technologies can enable improvements in productivity by streamlining workflows, reducing the manufacturing plant footprint and increasing flexibility. And while the benefits of next-generation processes are recognized, there are many options to consider and multiple pathways to success. We are developing technologies and approaches to intensify upstream and downstream processes, delivering both short term improvements as well as game-changing solutions to enable substantial gains over a longer timescale:
Perfusion operation allows for high-density cell cultures in both the seed train and production bioreactors, and can result in a 3-fold increase of volumetric productivity; media specifically designed for intensified perfusion further reduce costs and may increase volumetric productivity.
Use of a high cell density cryopreserved cell bank which feeds into the first seed train bioreactor can streamline the overall process. Specially-designed cryo bags eliminate open cell culture operation steps; a specially-designed medium is also necessary for high cell density cryopreservation.
Chemically-modified tyrosine and cysteine enable a single feed strategy at neutral pH of your fed-batch operations, simplifying fed-batch processes and enabling high available concentrations of both amino acids.
The use of dry powder media presents a number of challenges including, poor solubility, dust formation, caking, and low bulk density. Compaction of dry powder media strongly improves dissolution kinetics and enables safer, convenient handling.
A 2,000 liter bioreactor operating at 5 g/L has an approximate downstream buffer demand of more than 10,000 liters. The time and space required to produce, store, and then distribute this quantity of buffer can be significant, and so the use of buffer concentrates provides the opportunity to streamline the process, significantly reduces the facility footprint, and enables greater flexibility when switching over a production line. Current approaches to dilute these concentrates include in-line conditioning and in-line dilution.
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