iCONSENSUS

Biopharmaceuticals are large molecules used for the treatment of a broad spectrum of diseases including cancers and inflammatory diseases. They are produced using cells in bioreactors, where temperature, pH, oxygen levels, salinity and a whole range of other factors are carefully controlled to provide the best conditions for growth. Cell cultures are complex mixtures containing dozens of components (e.g., proteins, hormones, vitamins and elements) needed for the cells to grow. These components must be carefully controlled and monitored consistently within the bioreactors to produce quality drugs efficiently.

It can often be difficult to exactly replicate the conditions found in one bioreactor, and small differences from one product to another mean that the resulting drug cannot be used. The cell cultures within the bioreactor need to be monitored on a consistent and regular basis, and sensors need to be acutely primed to detect even the tiniest of changes, as it is easy for a batch to become degraded in quality thanks to one small change.

The iConsensus project developed a series of user-friendly miniaturised tools which can more accurately detect changes in the cell cultures in bioreactors, as well as monitoring the processes within the biopharmaceutical production line. These tools ensure that quality drugs are produced, while supporting a faster, safer and more cost-effective process for the production of biopharmaceuticals.

Tools for optimising cell cultures

The iConsensus project aimed to develop innovative tools for the development and monitoring of cell cultivation conditions in bioreactors offering better manufacturing control, ensuring the quality of the final product (biopharmaceuticals), and decreasing the duration and the costs of the process.  

For instance, the project developed optical online sensors to detect the level of oxygen in stirred tank bioreactors more precisely. They also developed similar sensors to detect the levels of carbon dioxide, which can be an important indicator of pH within a bioreactor.

A highly sensitive machine developed by Iprasense – the NORMA 4S – was developed to count both the density of cells within a given cell culture and the quality or viability of cells found there. For instance, if a bioreactor produces a high quantity of cells but all of those cells die within a few hours, then this is not such a high-quality result.

iConsensus also explored the idea of using different types of techniques to improve sensors. KTH and Kantisto, a SME specialising in chemical and pharmaceutical analysis, applied a separation technique called capillary electrophoresis (CE) to measure different components of the cell culture, like amino acids and sugars. They successfully put this on a chip, creating another tool to be added to the iConsensus toolkit.

Imaging analysis techniques like spectrometry, chemometry and fluorescence were used to identify problems in glucose, glutamate and lactate levels. Microfluidic immunoassays were deployed to ensure that glycosylation processes were proceeding normally – with correct folding etc.

The ALIAS system combined several of these tools so as to analyse a variety of different parameters at once while developing a biopharmaceutical. More than 10 analyses were successfully carried out 1-3 times per day on the sample.

Miniaturised innovation

The miniature tools that arose from the iConsensus project could be commercially available within 2-4 years, and they have a series of advantages associated with them. They are easier to implement because they are more automated than the current tools are, and the simplicity of the designs makes them user-friendly and will increase the robustness and the reproducibility of the results. They also make it possible for the cell culture to be analysed in real-time while providing better-quality information.

iConsensus largely dealt with the application of these tools for the production of monoclonal antibodies, glycoproteins and enzymes, however the results of iConsensus could also be applied to more nascent biotechnologies like gene therapies. As more and more drugs are developed using biomanufacturing, the outputs of the iConsensus project will lead to a process that is more efficient and more accurate with results that are of better quality and at a lower cost. By December 2023, the project published 17 articles in peer-reviewed journals as well as securing 5 application notes and a patent application.