Austrian University develops code to routinely simulate bioreactors

Graz University of Technology scientist’s new software can simulate the movements of microorganisms in the reactor within hours

Christian Witz from the Institute of Process and Particle Technology of Graz University of Technology at work, in front of a Plexiglas model of a stirred and fumigated (bio-) reactor

Scientists at Graz University of Technology in Austria have developed a simulation technology that aims to make the production of biopharmaceuticals more efficient, economical and understandable for the manufacturing industry.

The demand for biopharmaceuticals is huge, but while chemically manufactured drugs, " small molecules ", are relatively easy to produce and available in tablet form, biopharmaceutical preparation usually consist of many hundreds to thousands of atoms.

The production of biopharmaceuticals is therefore highly complex, carried out with the help of microorganisms in bioreactors using "trial and error".

"At the moment, the biotechnology industry still lacks in-depth process knowledge. You know that the manufacturing process works, but not why and how exactly it works, "explained Christian Witz from the Institute of Process and Particle Technology at Graz University of Technology.

Technology

Witz believes computer-aided simulations are the key to process knowledge and could significantly accelerate the process chain from laboratory to production. However, simulation programmes currently available on the market do not lend themselves to routine application: they require months of calculation, simulation expertise and a mainframe.

System will reduce the simulation time from months to hours

This is where Christian Witz's research comes in: He is working on a new, user-friendly and fast simulation software that will establish process simulation in the biopharmaceutical industry. "My system will reduce the simulation time from months to hours. It can also be operated by people without simulation knowledge and will run on standard graphics processors."

"The new software shortens the troubleshooting and promises a better understanding of the process. This makes the production of biopharmaceuticals more efficient," Wiz added. "Companies need fewer attempts to move from the laboratory to industrial production and save between three hundred thousand and one million euros."

Applications

Distribution of species in a stirred tank with a tilted stirrer axis. Credit: TU Graz

The basis for the new software is a joke-developed simulation code for stirred and aerated bioreactors, which has been in use in industrial research since 2017. This programme simulates, for example, the movements of microorganisms in the reactor or the spread of dissolved oxygen from the air bubbles.

As part of the ComBioPro (Computational BioProcess Design) project, Witz will now include additional algorithms in the software to implement the physical and biochemical processes in the bioreactor with more accuracy and user-friendliness.

Aims of the project include the partial automation of the evaluation of the raw simulation data as well as the simulation of very large air bubbles in the reactor. Based on the simulation results, design and production decisions can then be made. This would allow companies to simulate more projects in less time, and to test where and how productivity drops in the reactor.

Witz believes many questions can be answered with routine simulation. Such as:

  • How can one create conditions in the reactor where the microorganisms are most productive?
  • How do the speed of the stirrer or the gassing rate influence the process?
  • Where in the reactor do excessive shear forces act on the microorganisms?

University to commercial

Christian Witz has now been awarded funding for his project as part of the spin-off the Fellowship programme of the Austrian Research Promotion Agency FFG.

In 2021, the company plans to set up its own company, which on the one hand advises the biotechnology industry and carries out simulations on request. On the other hand, software licenses are also to be sold to those companies who, for example, do not share their geometry data and therefore want to work with the programme themselves. In the long term, Witz wants to become "the standard partner of the biopharmaceutical industry" with his company, whereby the simulation algorithms can also be applied to other technologies and industries.

The spin-off fellowship project ComBioPro is anchored in the Fields of Expertise " Human and Biotechnology " and " Information, Communication & Computing ", two of the five strategic areas of focus of Graz University of Technology.

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