Optical Spectroscopy Methods to Monitor Cells and Bacteria Concentrations and to Detect Contamination During Cell Culture: Application to the Fabrication of ATMPs

Currently, the production of Advanced Therapy Medicinal Products is highly sensitive to any contamination sources and therefore takes place in clean and sterile environments. Several days are required for each production, making these products extremely expensive. Throughout the process, numerous quality controls must be performed. This is especially true during the expansion phase in order to monitor cell growth and to detect any contamination. Bioreactor’s content must periodically be sampled to perform these controls. Two major drawbacks can be identified: a delayed knowledge of the quality control result and an additional risk of new contaminations due to sampling. In this work, we present optical spectroscopy methods which can be used to drastically reduce the risk of contamination. They provide a real time control of what happens in the bioreactor in a closed system manner. Cell concentrations are measured with an accuracy below 5% and contamination can be detected about 3 h after it occurred. The real time operation leads to several tens of thousand dollars’ savings because it allows stopping the production as soon as a problem arises. Consequently, the price of these products should be greatly reduced and they may be proposed to more patients.