When reading

Hans-Peter Meyer, Wolfgang Minas, and Diego Schmidhalter (2017) Industrial-Scale Fermentation. Industrial Biotechnology: Products and Processes, First Edition. Edited by Christoph Wittmann and James C. Liao. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2017 by Wiley-VCH Verlag GmbH & Co. KGaA.

I came across the following passage describing industrial up-scaling of fermentation processes (in general):


Process Development – Scale-Up Starts at Laboratory Scale

Process scale-up should be considered early on while the biological expression system is still under development. Factors such as genetic stability for at least the number of generations needed for a scaled-up production, and the need and impact on the environment of selection markers, should be evaluated before process development is started. The use of antibiotics as selective markers in the production medium should be avoided. Throughout development of media and cultivation conditions, it is important that parameter settings remain realistic and scalable, always indicated with upper and lower limits reflecting the safe operating range (process design space), for example, pH 7 ± 0.3.

I am quite surprised about the narrow pH range specified (pH $7 \pm 0.3$). I assumed that the pH range would be much wider, similar to lab scale. Is this really common practice?


Fermentation pH will differ a great deal depending on the bacteria or fungi being used and the process. But it is not uncommon to have a relatively narrow range of pH as a target. Remember pH is the -log[H+] so the pH scale is not linear. Also some fermentation reaction involve very expensive pharmaceuticals or intermediates, a single fermentation batch may have a value in the hundreds of thousands of dollars so keeping +/- 0.3 range in pH is trivial.

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