(313e) Mixing Scale-up for Aerobic Fermentations: From Lab to Pilot to Plant

Scale-up is critical to the successful commercialization of many chemical and biochemical processes. Failure to scale-up accurately will delay plant start-up and, consequently, product launch. Time and money must then be spent to rectify the operational plant-scale issues. This presentation discusses principles used to successfully scale between lab and plant scale mechanically agitated fermenters.

Processes are developed in the laboratory at small scale, typically 10’s of liters, then scaled-up to a pilot-plant, typically 1000’s of liters, and ultimately commercialized in a fermenter with an operating volume of 100000’s liters. The key parameters which must be held constant across the scales are the dissolved oxygen concentration, determined by the organisms’ requirements, and the oxygen uptake rate, determined by the desired growth and production rates.

A common method for scaling-up the gas flow rate is to maintain the ratio of the volumetric flow to liquid volume as constant. The gas flow rate can be expressed as vessel volumes per minute, or VVMs. If the oxygen consumption rate is the same across scales, this ensures that the composition of the exiting gas stream and the oxygen concentration gradient are the same.

Finally, there is some evidence that there is a minimum scale at which experiments can be conducted to assess mass transfer performance. The reason for this is that at small scales, there is significant surface motion which draws air down and this contributes to the concentration gradient with the air being fed to the fermenter and this results in the observed mass transfer coefficient being higher than would be expected with no surface motion. The rule-of-thumb recommendation is that the minimum scale is in the range 0.5 – 0.6 m.