Modeling of Biopharmaceutical Processes—Part 1: Microbial and Mammalian Unit Operations - Process-modeling tools can ensure smooth technology transfer of microbial and mammalian processes from b

ADVERTISEMENT

Modeling of Biopharmaceutical Processes—Part 1: Microbial and Mammalian Unit Operations
Process-modeling tools can ensure smooth technology transfer of microbial and mammalian processes from bench to commercial scale.


BioPharm International
Volume 21, Issue 6

In addition to facilitating liquid/ liquid mixing, agitation conditions can impact gas/liquid mass transfer. Oxygen is supplied and carbon dioxide (CO2) removed from most industrial cell cultures through sparging of gas bubbles through the bioreactor broth. The bubble gas/liquid mass transfer is a function of agitation conditions and the characteristics of the sparge gas inlet. The impact of these parameters on bubble gas/liquid mass transfer is most often described in terms of the mass transfer coefficient, kLaB:



in which P/V is the impeller power input normalized to liquid volume, Q is the sparge gas flow rate and k, α, and β are empirically fitted parameters. The fitted parameters can vary as a function of the sparge inlet characteristics, the most important of which may be orifice size. The size and number of air inlet orifices determine the superficial gas velocity and the resulting bubble size. Bubble size impacts the surface area to volume ratio of the bubble, and consequently the mass transfer efficiency. Smaller bubbles have a greater surface area relative to volume and hence they lead to more efficient mass transfer per volume of gas. Despite their mass transfer efficiency, very small (" 1 mm) bubbles are not favored for use in industrial mammalian cell culture for multiple reasons. A significant problem associated with sparging of mammalian cell cultures is cell death because of high shear, which occurs primarily because of bubble rupture at the liquid surface.14 Surfactants such as Pluronic F-68 are typically added to cell culture media to prevent cells from sticking to bubbles as they rise through the liquid, but damage can still occur to cells in the vicinity of bubble ruptures.15 Larger bubbles have lower maximum energy dissipation rates associated with bubble ruptures, which is consistent with literature observations that larger bubbles are less damaging to cell cultures.11 Further, small bubbles lead to less effective removal of carbon dioxide. Because of their high mass transfer efficiency, volumetric gas flow rates required to control dissolved oxygen at set-point are minimized, and hence, the bubbles saturate with a higher concentration of CO2. Accumulation of carbon dioxide can have a negative impact on the cell culture.16,17 By using larger bubbles, higher volumetric gas flows are required to control dissolved oxygen, and CO2 is more effectively removed.17 Finally, smaller bubbles lead to generation of more stable foam layers, and hence higher concentrations of antifoam may be required. For these reasons, larger bubbles (on the order of 5 mm) are preferred for industrial cell culture.11


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

PDA Announces Technical Report on Drug Shortages
September 9, 2014
European Commission Approves RoACTEMRA for Treatment of RA
September 9, 2014
DPT Laboratories Acquires Media Pharmaceuticals' Lakewood Facilities
September 5, 2014
Merck KGaA Breaks Ground on Facility in China
September 5, 2014
FDA Releases Guidance Electronic Submission of Lot Distribution Reports
September 5, 2014
Author Guidelines
Source: BioPharm International,
Click here