Scientists at the Cell and Gene Therapy Catapult in the U.K. cite using HemaCare leukopaks to study a new method of scrutinizing cellular quality markers during cell therapy bioprocessing. 
The publication represents a collaborative effort among scientists developing cellular therapies in the United States and Canada as well as in the U.K. They are working together to solve a key issue; how to ensure the consistent high quality of their living products.
The notorious variability of cell therapy starting material has frustrated scientists as new therapies emerge from small scale clinical trials into the wider world of the commercial sector. What was challenging to achieve in the labor-intensive atmosphere of a clinical trial can be even more difficult when a cellular therapy must be scaled up into what is necessarily a more automated, large-scale process. Not just quality but efficiency must be maintained to keep production of a cell therapy cost-effective.
Traditionally, scientists rely on off-line monitoring during process development. Basic quality markers such as viability, nutrient metabolism, and concentration, are tracked throughout the development process to monitor cell health. Generally, samples taken during the process are checked later to correlate quality markers with therapeutic performance. Being able to track key cell quality biomarkers during bioprocessing would both be more cost-effective and let scientists adapt and optimize process development more quickly.
In the present investigation, authors wanted to see whether they could make an in-line approach work. They chose HemaCare peripheral blood leukopaks as the starting material for their study, using cGMP collection guidelines. Primary T-cells were isolated from the starting material using a CliniMACS Plus system, and then activated and expanded on a BioBLU bioreactor system.
Quality assessment was carried out during expansion, using in-line optical sensors that collected “Raman spectroscopy” data every hour throughout the process. This type of spectroscopy uses laser excitation to collect chemical fingerprints of various important nutrient metabolites.  The study ran for 12 days in total, collecting data from 4 healthy starting material donors. Raman spectra were analyzed and interpreted using a specialized computer modeling system. The results were then compared to standard offline analysis of cell metabolism, viability, and proliferation.
The authors were successful in using their new in-line monitoring method to accurately track cell concentration, including cell proliferation rates and the overall T-cell proliferative capacity. They were also able to track nutrient depletion and metabolite production at a level comparable to the off-line analysis. The ability to track key markers of cell health and quality in real time offers significant progress in real time quality analysis and in the efficiency of cell therapy bioprocessing. This study provides excellent proof-of-concept for improving future cell therapy manufacturing processes.
- Baradez MO. et al. Application of Raman Spectroscopy and Univariate Modelling as a Process Analytical Technology for Cell Therapy Bioprocessing. Frontiers in Medicine. Mar. 2018.
- André S. et al. Mammalian cell culture monitoring using in situ spectroscopy: is your method really optimised? Biotechnol Prog. 33(2):308–16.10.1002/btpr.2430. 2017.