As we see more cell and gene therapies gaining market authorisation, attention is turning to the bioprocesses used for their manufacture, particularly the challenge of developing reliable manufacturing processes to ensure products are made to a constant quality.
Analytical challenges for cell and gene therapies
Analytical techniques can be used to control the manufacturing process through the measurement of critical quality and performance attributes. Many processes already incorporate off-line measurement of key markers such as nutrient consumption (glucose, glutamine), metabolite production (lactate, ammonia) and cell concentration. However, these often involve the removal of a sample from the process stream and are only performed at a limited number of time points during the manufacturing process. As a result, process decisions are often taken retrospectively regarding cellular events that took place hours or even days previously. Having the ability to monitor markers in real-time using in-line sensors would offer significant advantages, allowing faster decision making and a finer level of process control.
Raman spectroscopy: in-line monitoring
The analytical development team at Cell and Gene Therapy Catapult have been using Raman spectroscopy to monitor changes during the bioprocessing of cell therapies.
Raman spectroscopy works by measuring the wavelength and intensity of laser light that is scattered when it bounces of different molecules. This technology is increasingly being used to monitor biopharmaceutical production using CHO cell lines. However, this is the first report applying Raman technology to monitor cell therapy manufacture.
Using a T-cell immunotherapy model the team gathered the Raman spectra produced over a 10-day manufacturing process. Next, using reference data sets they identified the signals in the spectra corresponding to the nutrients and metabolites they were interested in and then modelled these spectra to track how they changed over time. Using this approach, they could monitor a wide range of markers simultaneously, in real-time and use the information to understand changes in cell behaviour and metabolism. This information could then be used to make process improvements.
New opportunities to improve the consistency of cell therapy manufacture
The ability to measure these key parameters using Raman spectroscopy makes it possible to have immediate feedback on process performance. This can significantly improve cell therapy bioprocessing and allow pro-active decision making based on real-time process data and is a significant step forward for cell therapy bioprocess monitoring.
Read the paper ‘Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing’ published in Frontiers in Medicine by following this link.