Magnus Ask1, Stuart M Stocks2. 1. Novo Nordisk A/S, Måløv, Denmark. 2. LEO Pharma A/S, Ballerup, Denmark. irkdk@leo-pharma.com.
Abstract
OBJECTIVES: Hydrodynamics, mixing and shear are terms often used when explaining or modelling scale differences, but other scale differences, such as evaporation, can arise from non-hydrodynamic factors that can be managed with some awareness and effort. RESULTS: We present an engineering approach to the prediction of evaporation rates in bioreactors based on gH2O/Nm3 of air entering and leaving the bioreactor and confirm its usefulness in a 28-run design of experiments investigating the effects of aeration rate (0.02 to 2.0 VVM), condenser temperature (10 to 20 °C), fill (2.5 to 5 kg), broth temperature (25 to 40 °C) and agitator speed (25 to 800 rpm). Aeration rate and condenser temperature used in the engineering prediction provided a practically useful estimate of evaporation; the other factors, while statistically identified as having some influence, were of negligible practical usefulness. Evaporation rates were never found to be zero, and could be at least 10% different to those expected at scale. CONCLUSIONS: An assessment of evaporation rates for any project is encouraged, and it is recommended that the effects are accounted for by measurements, modelling or by tuning the exhaust cooling device temperature to minimize scale differences.
OBJECTIVES: Hydrodynamics, mixing and shear are terms often used when explaining or modelling scale differences, but other scale differences, such as evaporation, can arise from non-hydrodynamic factors that can be managed with some awareness and effort. RESULTS: We present an engineering approach to the prediction of evaporation rates in bioreactors based on gH2O/Nm3 of air entering and leaving the bioreactor and confirm its usefulness in a 28-run design of experiments investigating the effects of aeration rate (0.02 to 2.0 VVM), condenser temperature (10 to 20 °C), fill (2.5 to 5 kg), broth temperature (25 to 40 °C) and agitator speed (25 to 800 rpm). Aeration rate and condenser temperature used in the engineering prediction provided a practically useful estimate of evaporation; the other factors, while statistically identified as having some influence, were of negligible practical usefulness. Evaporation rates were never found to be zero, and could be at least 10% different to those expected at scale. CONCLUSIONS: An assessment of evaporation rates for any project is encouraged, and it is recommended that the effects are accounted for by measurements, modelling or by tuning the exhaust cooling device temperature to minimize scale differences.
Authors: Cees Haringa; Wenjun Tang; Amit T Deshmukh; Jianye Xia; Matthias Reuss; Joseph J Heijnen; Robert F Mudde; Henk J Noorman Journal: Eng Life Sci Date: 2016-09-14 Impact factor: 2.678