CFD modeling and comparison of bioreactor performance across scales at Alvotech
(2022) MVKM01 20222Department of Energy Sciences
- Abstract (Swedish)
- At Alvotech, bioreactors are used for the production of biosimilars. During the production scale-up process, issues can arise at larger scale that are difficult to predict based on physical experiments. Using CFD, two 3D bioreactor models of different scales have been created, namely the 15L HyPerformaTM Glass Bioreactor and 250L HyPerformaTM Single-Use Bioreactor, both manufactured by Thermo Fisher Scientific, with the aims of comparing mixing performance across scales. The bioreactors share geometrical similarities and are both stirred with a single down-pumping Elephant-Ear impeller. The SST k-w turbulence model is used for modeling the turbulent flows and the Euler-Lagrangian DPM model is used for modeling multiphase flows with oxygen.... (More)
- At Alvotech, bioreactors are used for the production of biosimilars. During the production scale-up process, issues can arise at larger scale that are difficult to predict based on physical experiments. Using CFD, two 3D bioreactor models of different scales have been created, namely the 15L HyPerformaTM Glass Bioreactor and 250L HyPerformaTM Single-Use Bioreactor, both manufactured by Thermo Fisher Scientific, with the aims of comparing mixing performance across scales. The bioreactors share geometrical similarities and are both stirred with a single down-pumping Elephant-Ear impeller. The SST k-w turbulence model is used for modeling the turbulent flows and the Euler-Lagrangian DPM model is used for modeling multiphase flows with oxygen. Both models are validated against experimental data on mixing time and kLa, whereby simulations are run using operating conditions from experiments at Alvotech. The parameters investigated for mixing performance include mixing time, shear exposure, and gas distribution. The 250L pilot scale bioreactor has a predicted mixing time that is three times that of the 15L bench scale bioreactor, but shows no significant decrease in mixing performance with regards to shear exposure or gas distribution. (Less)
- Popular Abstract
- During bioreactor scale-up, unexpected failures become more prevalent due to the increase in volume. A comparison of mixing performance was thus made using computational modeling for two bioreactors at different scales.
At the biopharmaceutical company Alvotech, bioreactors are used at different scales for producing biological medicines known as biosimilars. Bioreactors are vessels containing a mixture of fluids, gases and biological material, such as cells. They are designed to promote homogeneous mixing while limiting potential damage due to stress on sensitive cells in the vessel. Development of biosimilars starts at small volumes to identify optimal process parameters, whereafter the established process is scaled up to larger... (More) - During bioreactor scale-up, unexpected failures become more prevalent due to the increase in volume. A comparison of mixing performance was thus made using computational modeling for two bioreactors at different scales.
At the biopharmaceutical company Alvotech, bioreactors are used at different scales for producing biological medicines known as biosimilars. Bioreactors are vessels containing a mixture of fluids, gases and biological material, such as cells. They are designed to promote homogeneous mixing while limiting potential damage due to stress on sensitive cells in the vessel. Development of biosimilars starts at small volumes to identify optimal process parameters, whereafter the established process is scaled up to larger volumes for production.
At larger scale, unexpected failures can arise due to bioreactors behaving differently at different volumes. Additionally, as the bioreactor volume increases, it becomes increasingly time consuming and costly to characterize fluid flows experimentally. Resultingly, risks increase with experimental methods at large volumes. Physical methods are thus moving towards in silico trials, such as with computational modeling and simulations. By the use of simulations, unexpected failures during production scale- up can be predicted and avoided, minimizing risks at larger scale. This approach not only reduces the time and costs of product development, increasing the accessibility of medicines, but also maximizes product quality by identifying problems early in the process.
In this study, fluid characteristics of two bioreactors of different scales were simulated using Computational Fluid Dynamics (CFD). The aim was to compare mixing performance of the two vessels, to predict whether the larger bioreactor (pilot scale) showed a decrease in performance compared to the smaller bioreactor (bench scale) with regards to mixing time, shear exposure and gas distribution in the vessels.
Findings were that both bioreactors showed similar mixing characteristics for the given operating parameters used in experiments at Alvotech. Looking at the shear exposure and gas distribution, the pilot scale bioreactor showed no significant decrease in performance compared to that of the bench scale bioreactor. Simulations of the pilot scale bioreactor predicted mixing times three times longer than for the bench scale bioreactor, however this would be expected given the scale-up approach used at Alvotech and due to the large increase in working volume. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9103944
- author
- Hörwing, Hanna LU
- supervisor
- organization
- course
- MVKM01 20222
- year
- 2022
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- CFD, bioreactor, scale-up, mixing, mixing time, shear stress, Elephant-Ear impeller, SST, Euler-Lagrange, DPM.
- report number
- LUTMDN/TMHP-22/5508-SE
- ISSN
- 0282-1990
- language
- English
- id
- 9103944
- date added to LUP
- 2022-12-19 14:08:24
- date last changed
- 2022-12-19 14:08:24
@misc{9103944,
abstract = {{At Alvotech, bioreactors are used for the production of biosimilars. During the production scale-up process, issues can arise at larger scale that are difficult to predict based on physical experiments. Using CFD, two 3D bioreactor models of different scales have been created, namely the 15L HyPerformaTM Glass Bioreactor and 250L HyPerformaTM Single-Use Bioreactor, both manufactured by Thermo Fisher Scientific, with the aims of comparing mixing performance across scales. The bioreactors share geometrical similarities and are both stirred with a single down-pumping Elephant-Ear impeller. The SST k-w turbulence model is used for modeling the turbulent flows and the Euler-Lagrangian DPM model is used for modeling multiphase flows with oxygen. Both models are validated against experimental data on mixing time and kLa, whereby simulations are run using operating conditions from experiments at Alvotech. The parameters investigated for mixing performance include mixing time, shear exposure, and gas distribution. The 250L pilot scale bioreactor has a predicted mixing time that is three times that of the 15L bench scale bioreactor, but shows no significant decrease in mixing performance with regards to shear exposure or gas distribution.}},
author = {{Hörwing, Hanna}},
issn = {{0282-1990}},
language = {{eng}},
note = {{Student Paper}},
title = {{CFD modeling and comparison of bioreactor performance across scales at Alvotech}},
year = {{2022}},
}