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Connell-Crowley, Lisa

Dell, Brad

Follstad, Brian

Ford, Chris

Kitchen, Neil

Piper, Rob

English

Engineering Conferences International

 Poster Number 54 CONVERSION OF AN INTENSIFIED FED-BATCH TO AN INTEGRATED CONTINUOUS BIOPROCCESS  Brian Follstad, Just – Evotec Biologics, Inc., USA brian.follstad@justbiotherapeutics.com Chris Ford, Just – Evotec Biologics, Inc., USA Brad Dell, Just – Evotec Biologics, Inc., USA Neil Kitchen, Just – Evotec Biologics, Inc., USA Rob Piper, Just – Evotec Biologics, Inc., USA Lisa Connell-Crowley, Just – Evotec Biologics, Inc., USA   Key Words: mammalian cell culture, fed-batch, continuous, bioreactor, product quality  Recent advances in upstream and downstream Integrated Continuous Bioprocessing (ICB) technologies and their subsequent impact on reducing manufacturing costs have generated increased interest in ICB as a platform bioprocessing format (Coffman et al, 2021 and Mahal et al, 2021).  However, process development costs continue to be a concern with ICB, particularly for the conversion of a process originally developed as a fed-batch (FB) or intensified fed-batch (IFB) process into a hybrid or end-to-end ICB process.  The conversion of the production bioreactor step from a short duration FB process to one involving longer duration perfusion or continuous operation is manageable with a high specific productivity cell line, a low-cost, concentrated perfusion medium, and an optimized cell-retention device platform, but the impact to product quality stemming from higher culture cell densities and longer culture durations remains as a potential challenge for purification processing requiring additional upstream process development.  This work covers the conversion of an IFB mAb process to an ICB process, implementing the Just- Evotec Biologics platform, that was driven by the need for a significant increase in process productivity over a short development time (< 6 months from project start to cGMP batch completion) with minimal risk due to changes in product quality.  The project’s upstream-related challenges primarily involved addressing filter fouling concerns due to higher cell culture densities and durations; however, with minimal changes to the production bioreactor platform process setpoints, the process was successfully scaled-up from bench to manufacturing (500L) scale resulting in an over 5-fold increase in product mass per working volume basis as compared to the IFB process.  The drug-substance product quality was comparable for most attributes (HMW and rCE) and process impurities (HCP, DNA, and Pro-A) with some minor differences in glycan distribution resulting in the need for a follow-up study determining the potential impact on the product residual effector function.  These results demonstrate that the biotherapeutics industry’s need to quicky adapt to changing clinical and business circumstances that require the rapid conversion of FB and IFB mAb processes to ICB can be met when implementing a robust ICB platform.         

Conversion of an intensified fed-batch to an integrated continuous bioprocess

https://dc.engconfintl.org/cgi/viewcontent.cgi?filename=0&article=1087&context=biomanufact_v&type=additional

Conversion of an intensified fed-batch to an integrated continuous bioprocess

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Engineering Conferences International