Single-use disposable technologies have seen rapid growth and expansion in the production of mammalian cell culture-derived biologics.  Decreased cross-contamination risks and ease of operational requirements have encouraged many organizations to rely heavily on single-use systems from bench through GMP production scale.  Despite the ubiquitous application in mammalian biologics production, substantial growth of single-use systems in fermentation-based production has been trailing.  Fermentation process inputs, including high oxygen mass transfer rates, mixing requirements, and high growth rate demands, have made disposable fermentation systems challenging to implement as viable production solutions.  KBI Biopharma has recently expanded its process capabilities to include single-use fermentation (SUF) systems at the 30 L Pilot and 300 L GMP manufacturing scales.  Coupling ThermoFisher Scientific SUF systems with a platform <i>E. coli</i> process development approach and advanced mass transfer modeling, KBI is significantly shortening process design to GMP production timelines.  Fermentation process conditions, oxygen uptake requirements (OUR), media types, and feed strategies are initially defined in the high-throughput Sartorius Ambr250 system to fit the ThermoFisher 30 L and 300 L SUF systems.  Feed profiles are established to maximize cell densities with controlled aeration strategies not to exceed the mass transfer capacities of the SUF systems.  The scalability of the Ambr250 system to the ThermoFisher 30 L and 300 L SUF systems, combined with the KBI platform process design approach is yielding protein titers greater than 4 g/L for soluble products at the 300 L GMP scale.  The multiplexed approach, combining end-to-end SUF systems with platform process design and advanced system modeling, offers tremendous potential for rapid process design with simple scale-up and translational solutions to enable GMP production.

Implementation of end-to-end disposable single use systems for rapid fermentation process design to GMP manufacturing

2019 Spring National Meeting

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