Student: My name is Gerard Chan. I am an alumnus of UCL Biochemical Engineering and graduated from my EPSRC-sponsored EngD with Westfalia Separators (now GEA) (Dr K Mannwailer) and UCL (Prof. M Hoare) in 2007. I’m currently pursuing my Chartered Engineer status from IChemE. After leaving UCL I worked in fermentation process development at Cobra Bio-manufacturing, where much of my work centred around optimisation and developing process strategies for clients. A year later I moved on to project management for Novartis Vaccines, where I now look after the upstream operations. Westfalia Separators are a leading supplier of centrifuges to the biotech and biopharmaceutical sector. Novartis Vaccines is a world leader in the vaccines market, with the Liverpool site supplying the US market with ~50 million doses of Fluvirin/year and stockpiles of h5n1 vaccine.
Background: The use of high-speed continuous centrifuges for the recovery of cells is often a key first stage of downstream processing. A previous EngD programme (Nick Hutchison with Lonza Biologics) successfully demonstrated the use of a high-speed shear device to mimic the feed zone in continuous centrifuges. Nick was able to work with both the Slough (UK) and the New Hampshire (US) teams to verify his predictions for the industrial-scale recovery of mammalian cell broth (Hutchinson et al, Biotech Bioeng 2006 95, 483).
The challenge: My project addressed harvesting cells containing intracellular products where the concern was the integrity of the cells on discharge. The cells I examined were recombinant E. coli producing either plasmid DNA or an antibody fragment (kindly supplied by UCB Celltech). The challenge was to create a fundamental understanding of the discharge mechanism and the creation of an ultra scale-down of sediment recovery in an intermittent discharge disc stack centrifuge.
Issues that arose: a) the extremely complex hydrodynamics occurring during discharge which led me to a study of how high pressure water jets are used for cleaning buildings! b) the challenges of analysis of the impact on stress on cells and especially the subtle effects on cellular location of the product; c) the ability to control the operation of the disc stack centrifuges to verify my ultra scale-down predictions.
Results: A high-pressure capillary-based impact flow device was created to mimic the centrifuge discharge zone (Chan et al, Biotech Bioeng 2006, 95, 671). I worked with colleagues at Westfalia Separators to interpret the consequences of my findings and was able to predict and verify at pilot scale using the UCL facilities how damage to the cells can be prevented by attention to the operation of the disc stack centrifuge. I also gained insight into the new generation of high performance cell dewatering devices and as a result of my research UCL was able to install an advanced machine in their large scale facilities for bioprocessing research and use on training programmes for undergraduate, Masters and postexperience (MBI®) beneficiaries.
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