11
Scale-up of bioprocesses
The previous chapters in this book have concerned stoichiometric, thermodynamic and kinetic
analysis of the production microorganisms, as well as the operation o f small-scale bioreactors.
This is a necessary basis for exploitation of microorganisms in fermentation processes. The
ultimate goal for process development is, however, the realization of a large-scale production.
Scale-up is a very difficult task. Certainly, you would like to follow the advice given by H.
Baekeland, the inventor of Bakelit, in 1916:
“Commit your blunders on a small scale and make
your profits on a large scale
One might regard scale-up as more an art than a science (Humphrey, 1998). This should not be
understood in the sense that good engineering judgement is not helpful, on the contrary.
However, many different aspects need to be taken into account (Leib et al., 2001), and the final
scale-up will necessarily be a delicate compromise between inherently conflicting desirable
characteristics. Certainly, this is a task for the experienced engineer. The purpose o f this chapter
is to give an understanding of the fundamental problems that arise when a process is scaled-up,
and to provide some useful tools for analysis of critical scale-up factors.
11.1 Scale-up Phenomena
Production strains are normally first selected in the laboratory, under conditions different from the
conditions in the production scale. Subsequently, the strain is tested in a number of bioreactors of
increasing scale, and the final process verification is earned out in a pilot plant (reactor scale 50-
3000 L). A considerable scale-up of the process can be said to take place already in the lab. The
scale o f operation changes significantly when a culture is taken from a petri-dish via a shake
flask culture to a small-scale bioreactor. The environmental conditions for growth on a petri-dish
are very different than those for growth in an E-flask culture, which in turn are rather different
from those in a small scale aerated bioreactor. Normally, however, the term scale-up is used for
the step from small scale to production scale. Using the definition by Bisio and Kabel (1985)
scale-up can be defined as: “The successful startup and operation of a commercial unit whose
design and operation procedures are in part based upon experimentation and demonstration at a
smaller scale of operation
.’1
Scale-up does not only involve pure engineering considerations, but
certainly also economic considerations. For instance, a new medium formulation may be found
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