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As part of an international consortium, the bioprocess engineering group of Wageningen University & Research work on process development for the production of pharmaceutical proteins and vaccines using CHO cells and the baculovirus expression system. As the COVID-19 vaccination efforts continue worldwide, Hamilton Process Analytics got the chance to speak with Jort Altenburg, a Ph. D candidate at University in Wageningen in the Netherlands. He explains why vaccine production is not simple and talks about the challenges he is facing in his research and the solutions he has found.

Jort Altenburg holds a Master of Science in Biotechnology and works as a PhD student in the research group of Prof. Dirk Martens at the University in Wageningen, The Netherlands. Previously, he worked as a scientist at MSD and as a sales engineer at Applikon in the Netherlands.

Jort, your work is embedded in an international project to develop vaccines against covid-19. What exactly is the goal of your development?

Our goal is to produce vaccine material for pre-clinical trials and develop a scalable production process for technology transfer to larger scale GMP production. We use the baculovirus insect cell expression system to produce the SARS-CoV2 spike proteins in bioreactors. In order to produce spike proteins in sufficient amounts, we need to know the optimal production strategy to apply in the bioreactors.

What does your work consist of?

We operate different kinds of bioreactors, from orbital shaken screening microbioreactors to larger scale stirred tank reactors. The microbioreactors are used to screen for optimal process conditions. Then we scale up to stirred tank bioreactors using the most promising settings and virus strains. The larger bioreactors allow us to add more sensors and take larger samples, thereby giving us more information on the process.

What is the particular challenge of your work?

Time, or the lack thereof, is a very important factor in this project. Due to the urgency of the pandemic we do not have time to do a lot of extra experiments. So we have to make important process decisions with limited time and information available. These decisions can have implications further on in the process so it is important to generate as much information as possible from the set of experiments we can execute. Therefore, we rely heavily on on-line sensors who provide us continuous data in real time.

What methods do you use to monitor cell density?

We determine cell counts of bioreactor samples. In addition, we use holographic microscopes that continuously visualize the cells and we monitor off-gas concentrations of O₂ and CO₂ coming from the bioreactors.

Which Hamilton sensor did you use in the project?

We used the Incyte Arc Sensor to monitor the viable cell density. It is very easy to install in a bioreactor and connect to the monitoring software. After performing a baseline calibration in medium, you are ready to monitor your bioreactor run.

What do you think is the advantage of the sensor?

The measurement is non-invasive, which allows you to easily integrate the sensor with minimal impact on your process. The continuous monitoring allows you to obtain high resolution data on the state of your cell culture. When monitoring established processes, this high resolution allows you to quickly spot process deviations and you can control your process or intervene based on this data. When running an experimental process, the high data resolution gives you more understanding of what is happening in the process. This can speed up your process development considerably.

Do the data show the hoped-for results?

The data was very accurate compared to our offline methods and we were surprised by the amount of detail in the measurement signal. We were able to see some events happening in the bioreactor that we previously did not notice. This gave us new insights on the impact of some of our process strategies. Since the data was so accurate during the whole process, it can give us a good indication on the optimal timing of certain events, such as when to harvest or when to infect the insect cells with baculovirus. In the future the incyte sensor would be a valuable addition to other on-line measurements to control our process

Jort, thank you for the interview and we wish you every success!

"The difference in measurement resolution between the off-line method and permittivity is like between a 60's TV and an 8K screen!"

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To learn more about this exciting project, please visit the University's website.