Optical Spectroscopy for the Quality Control of ATMP Fabrication: A New Method to Monitor Cell Expansion and to Detect Contaminations

Fabrication of Advanced Therapy Medicinal Products takes currently place in clean and sterile environment and is highly sensitive to any contamination sources. It lasts for several days and is extremely expensive. Quality controls must be performed throughout the process, especially to monitor cell growth during the expansion phase and to detect any contaminations. Regular sampling of the bioreactor's content is required and subsequent biological investigation are conducted. Major drawbacks are first, a delayed result of the quality control and second, an added risk to induce new contaminations when sampling the content of the bioreactor. Here, we present a real time optical spectroscopy method which can be used in a closed system manner, hence reducing the risk of sampling-related contamination. Analysing the shape of the absorption spectrum of the bioreactor content allows monitoring the cell growth and alerting users in case of contamination. Cell concentrations are measured with an accuracy off 5% and contamination can be detected about 3 hours after it occurred. This allows stopping the fabrication as soon as a problem arises leading to several tens of thousand dollars savings. Consequently, the price of these products should be greatly reduced and they may be proposed to more patients.