Previously, the consortium had successfully transferred a TIL manufacturing process into a dynamic stir-tank bioreactor system enabling integration of PAT biosensors such as Raman Spectroscopy and 2D fluorescence. Using a TIL-like healthy donor model in this system, we applied complex design of experiment (DoE) approaches to screen and validate critical process paraments (CPPs) identified through metabolomics studies performed at the Hospital Universitario La Fe (HULAFE) in Spain, process development studies at Cell and Gene Therapy Catapult (CGT Catapult), and literature research. These DoE studies enabled us to develop an improved process with better cell expansion and cell reactivity. 

Furthermore, the consortium had successfully achieved the integration of both Raman spectroscopy and 2D fluorescence sensor systems, which are used for real-time process monitoring and implementation of an adaptive control strategy.  Lastly, it had set up a digital infrastructure at CGT Catapult’s labs in London at Guy’s hospital, enabling continued digitalisation of the cell and gene therapy sector. Part of the digital infrastructure set up included the integration of a 2D fluorescence sensor system developed at the University of Hannover (LUH) into the bioprocess platform. Multiplexing of flow cells for online fluorescence measurements is enabling the development of an online cell count model to be available for up to four vessels simultaneously. This will be used for automated process control. 

The team has been busy the last 3 months to design and implement the experiments aiming to demonstrate a proof-of-concept of adaptive process control. With the support of the Partner in Hannover (LUH), we created in silico simulations of model-based bioprocess optimisation that enabled us to significantly shorten the process time by 4 days while maintaining the required product’s critical quality attributes. We are now in the latest development stages of this smart TIL process to demonstrate PAT-driven advanced and adaptive process control on the healthy-donor model. We will then apply this proof-of-concept system to patient-derived samples to verify applicability of this smart process on real-world clinical material. 

Consortium team members have been travelling across Europe and the US to share project key findings in Cell and Gene Therapy conferences. A Poster “Towards industry 4.0: development of a smart bioprocessing platform  integrating real-time monitoring and advanced process control for autologous cell therapy”  was presented at the 10^th Bioproduction Conference (BIOP) in Lyon (see Poster here), France (22-23 September 2025).