Monoclonal antibodies can be produced in culture fluid by the fermentation of specificially selected hybridoma cells. Hybridoma cells exhibit suspension type fermentation characteristics and therefore the simplest method for large scale fermentation is that of the stirred tank fermenter. However, such is the growing demand for monoclonal antibodies, methods for increasing the production capacity of a commercial process are being developed. This study examines some of the current process intensification methods in relation to an established production facility. As well as examining the actual productivity increases possible with any method, the applicability of that method to a commercial environment is taken into account. Hollow-fibre systems are investigated, with a potential increase in productivity which was outweighed by the significant retooling and retraining costs. Gel Bead entrapment systems are shown to have great promise, as they can be readily placed into existing equipment and production methods. However, all methods examined, including alginate bead entrapment, were found unsuitable for hybridoma cell culture. A novel method for cell entrapment was developed, using an agarose/alginate gel mixture which allowed greatly improved growth and consistent antibody production. The entrapment method was examined in a continuous chemostatic system. This system was then scaled-up and applied to the existing facility, to give a 25L airlift operating in a chemostatic mode at a rate of 1.2-1.5 day<SUP>-1</SUP>.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:663911 |
| Date | January 1992 |
| Creators | Wilson, James Samuel |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12155 |
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