Simulation of pH level distribution inside a coiled flow inverter for continuous low pH viral inactivation
| Autor: | Martin Lobedann, Laura David, Lisa Marie Waldschmidt, Gerhard Schembecker |
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| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
0301 basic medicine Materials science Flow (psychology) Mixing (process engineering) Bioengineering Computational fluid dynamics Residence time (fluid dynamics) 01 natural sciences Applied Microbiology and Biotechnology Continuous production Chromatography Affinity 03 medical and health sciences Sine wave 010608 biotechnology Computer Simulation Staphylococcal Protein A Steady state Elution business.industry Equipment Design Hydrogen-Ion Concentration 030104 developmental biology Hydrodynamics Virus Inactivation Biological system business Biotechnology |
| Zdroj: | Biotechnology and bioengineeringREFERENCES. 117(2) |
| ISSN: | 1097-0290 |
| Popis: | The continuous production of monoclonal antibodies (mAbs) with the help of disposable equipment poses one of the future major changes in the pharmaceutical industry. Consequently, continuous viral clearance needs to be developed as well. The coiled flow inverter (CFI) was successfully implemented in the continuous downstream as a residence time module for low pH viral inactivation. As the elution profile of the upstream continuously operated protein A chromatography results in fluctuating pH values, the pH level distribution inside the CFI is highly relevant. This study presents a detailed investigation of pH level distribution inside the CFI at varying inlet conditions with the help of computational fluid dynamics simulation. The simulation model was validated first with the help of experimental data. Afterwards, the model was used for further investigations. It was determined that with a pH sine curve as input, the duration until steady state at the outlet requires two times the minimum residence time of the apparatus. Moreover, it could be observed that the CFI itself offers a progressive dampening effect on the pH level distribution. Afterwards, different forms of the sine curve representing different operation modes of the continuous protein A chromatograph were tested to evaluate this dampening capability. It became clear that the switch time has the highest influence on the resulting pH of the outlet stream and should be considered for process development. Finally, the radial pH profiles at different positions inside the CFI were determined. This once again revealed the high radial mixing capability of the CFI and its influence on the resulting product stream. |
| Databáze: | OpenAIRE |
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