Table 2.

Scale-dependent fermentation parameters.

Parameter	Deviation	Impact
Raw material grade	Industrial vs. reagent grade, purity, concentration, lot-to-lot variability	Accumulation of inhibitors and unfermentable components can negatively impact fermentation, downstream processing (DSP), and waste water treatment (WWT); differences in concentration can impact water balance and time course dynamics for fed-batch processes
Raw material sterilization	Batch vs. continuous sterilization, temperature and residence time profiles	Component degradation and/or inhibitor formation can negatively impact fermentation, DSP and WWT
Fermentor mixing time	Increase in magnitude	Gradients in critical process control parameters (e.g. temperature, pH, substrate or nutrient concentration) can negatively impact fermentation performance
Gas-liquid volumetric mass transfer coefficient (kLa)	Gradient due to power dissipation; upper limitation due to equipment design	Both limitations and gradients in mass transfer rates can negatively impact fermentation performance
Broth hydrostatic pressure	Increase in magnitude with gradient along vertical axis	Elevated gas partial pressures (e.g. pO2, pCO2) and gradients in partial pressures and dissolved gases can impact fermentation performance
Shear stress	Increase in magnitude	Higher shear stress can cause cell damage, affecting fermentation and/or DSP performance
Broth handling	Extended broth holds and harvest times	Residence time and conditions (temperature, aerobicity, product concentration) can impact cell lysis and broth chemistry, which can negatively impact DSP and WWT
Broth deactivation	Batch vs. continuous deactivation, temperature and residence time profiles	Deactivation conditions (time, temperature) can impact cell lysis and broth chemistry, which can negatively impact DSP and WWT