More Efficient Drug Production Using Cloud-Based CFD Simulation of Bioreactors

 Aerated stirred reactors, the most common type of both small- and large-scale bioreactors, are used for performing microbial fermentation or mammalian cell culture unit operations for the production of biological therapeutics such as vaccines, hormones, proteins and antibodies. Usually, basic design criteria have been adapted in such a way as to meet the requirements of cells. In particular, the shear sensitivity requires consideration in impeller design, aspect ratio and aeration. Sufficient oxygen transfer and carbon dioxide removal are very important criteria in selecting a bioreactor system. Taking into account the process criteria, the scale-up process of bioreactors still presents a challenge and requires detailed knowledge about diverse fields such as the mixing processes, agitation, aeration, heat and mass transfer, etc.

 

Challenge
The main challenge in the calculation is the treatment of multiphase systems and long process time of several hours which leads to long calculation time, which is not suitable for industrial application. In order to overcome these limitations and to apply CFD simulations in the development process, a highly optimized workflow and huge computational resources are required. For instance, an estimation of the oxygen mass transfer coefficient for only 1 variant takes about 1 week of computational time (using a single computer with 12 CPUs). This is mainly caused by the need to run transient simulations up to 20 seconds. The time must be completely simulated and in addition the simulation has to run with very small time steps caused by multiphase simulations (e.g. 0.01s).

Business impact
The computational time for design of experiments (DoE) analysis was decreased from 5 weeks to 1 week. Due to huge computational resources in the cloud, all 25 simulations variants can be run in parallel and not one after the other. This number of variants are typical for DoE analysis, but are not limited anymore thanks to Cloud-based technology. Furthermore, the number of simulation variants is no longer related to the in-house hardware resources and therefore no investments are needed. Finally, each bioreactor manufacturer can benefit from proven and validated simulation technology and workflows for this kind of application.

Using the Cloud-based simulation technology it is possible to carry out analysis of bioreactors with clearly reduced costsdue to reduced calculation time of parallel simulation variants and full cost control. Through the parallel calculation of a huge number of variants in a very short calculation time it enables the opportunity to get new customers. Addressing a customer segment defined by the pharma, biopharma, automotive and general engineering industries, in a three-year horizon SES-Tec estimates to face a market size of around 4.7 billion dollars, with a potential share reaching 20,000-50,000 euros/year and leading to an increase of 15 percent of actual turnover due to only Cloud computing. Furthermore, SES-Tec is planning to hire a new employee, which deals exclusively with cloud computation.

Organizations involved
SES-Tec OG- Austria
AVL List GmbH- Austria
Arctur - Slovenia