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Staff in Development Fermentation use shake-flask data from Microbiology as a starting point to develop fermentation processes for our production facility. Processes are developed in our lab-scale (20 litre) fermentation vessels. Modifications are made to media recipes to suit fermenter operations. Cultivation in stirred fermenters offers the possibility of much greater process control than is the case in shake flasks. Temperature, pH, dissolved oxygen, agitation, airflow, head pressure can all be controlled; depleted nutrients can be replaced by fed batch operation. Physical and chemical parameters need to be optimized for growth and productivity. Scale up to full scale equipment (up to 30,000 litres at AFI) is facilitated by trials in our intermediate pilot scale vessels (150, 200 & 1500 litre vessels). Pilot scale vessels are also used for small scale cGMP manufacturing. All our vessels are controlled by digital controllers interfaced with computers for continuous acquisition of online data and for process control. Analytical Chemistry performs chemical analyses of off-line samples. Development Fermentation is also equipped with pilot scale cell separation equipment including a pilot scale filter press and disc stack centrifuge. Development work at all stages is carried out in close cooperation with Organic Chemistry staff as operational changes in fermenters can have a profound effect upon impurity profiles of crude broths, making downstream operations easier or more difficult.
Development Fermentation resources include eight 20 litre, one 150 litre and one 1500 litre fermenters, all digitally controlled and interfaced with computers for data acquisition and control, plus a 200 litre vessel with analogue controls. Supporting equipment includes IR sensors for monitoring exhaust gas CO2, a 6 cu. ft. filter press with membrane squeeze capability and a pilot scale disc stack centrifuge. When necessary, trials can be run under protocol in full-scale production fermenters up to 30,000 litre capacity.
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