Scale up of fermentation process
and fermentations
Scaling up in Bioprocess
• Scale-up is the process of expanding a fermentation
process from a smaller-scale fermenter, where
operational and production parameters have been
studied, to a larger scale.
• Engineers must take into account all aspects that affect
the integrity of the fermentation during the scale-up
process.
• These aspects include physical (namely, heat and mass
transfer phenomena such as oxygen transfer rates and
mixing time), biochemical (such as medium
compositions and rheology), and process (such as
conditions of the pre-culture and inoculum) factors.
• However, the kinetic behavior of microorganisms is affected
by local environmental conditions such as nutrient
concentration, pH, temperature, dissolved oxygen, etc. It is
well known that microorganisms are more sensitive to these
environmental variables in a large scale.
• Physical factors include mass and heat transfer conditions,
mixing (agitation) conditions, shear stress regimes, power
consumption, pH, temperature, dissolved oxygen, etc.
• Biochemical factors mainly are medium components and
their concentrations along with their physiochemical
properties.
• Finally, process factors including pre-culture conditions,
sterilization quality, and inoculation ratio also dictate how
successful scale-up is implemented.
Purpose
Pilot Scale
Scaling up in Bioprocess fermentations
• The traditional method for scale-up of a fermentation
process involves determining the reactor geometry, impeller
speed, and aeration rate of the large-scale bioreactor on the
basis of the experimental results of the lab-scale bioreactor.
• The most common method of scale-up is based on
maintaining geometric similarity of bioreactors.
• Once the volume of the large-scale bioreactor has been
chosen, its geometric parameters, namely, tank height, tank
diameter, and stirrer dimension, can be estimated.
• The typical methods of determining impeller speed and
aeration rate are dependent on empirical correlations to
keep relevant parameters constant with the change in scale.
• Evaluation of impeller speed is based on
keeping agitation power input per unit
volume (P/V), volumetric oxygen mass
transfer coefficient (kLa) constant.
Physical Properties
• Mass and heat transfer along with mixing conditions
(or flow behavior) are the physical properties that
affect scale-up strategies.
• In most fermentation processes, the heat generated by
catabolism is taken into account with heat transfer
rates in large-scale bioprocesses.
• Oxygen transfer rate (OTR) that controls oxygen uptake
rates (OUR), especially in aerobic fermentations where
oxygen is limiting, is another crucial factor in scaling up.
kLa (h−1): volumetric oxygen transfer coefficient
Mixing Time
• Engineers may choose to scale up based on
equal mixing or blending time.
• Mixing time can be defined as:
