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One of the first steps is to establish a reliable scale-down model in the bench-top reactors. We have used the XDR-10 in the scale-down mode to design and predict what we will see in the large scale systems. The control methods and hardware are critical. Special attention should be given to the dissolved gasses, both pO2 and pCO2, as these parameters will affect the amount of base required as well. You should examine a sparge porosity you are likely use at large scale. This way you can get a relative understanding of the volume to volume gas requirements. This will also provide process information on the amount of foam that may be generated. Further, this will give an early look at the potential impact of interfacial shear resulting from the sparging. The agitation rate (rpm) should also be closely considered. Often times stress on the cells/culture can alter metabolite profile.