The regenerative medicine industry requires the manufacture of high quality medical products at an economically acceptable cost. The safe and reproducible delivery of a commercially viable and clinically effective regenerative medicine product is key to its success. In-process characterisation of the cell component, scaffold and combined product will allow efficient and precise process development and will enable process analytical technology for manufacture to be selected on the basis of the most useful data. Rapid identification of deviation during manufacture will allow a corrective in-process response to be made, reducing failure rates and decreasing the dependence on end-product testing; this will positively impact both risk and cost of manufactured product.
Case studies
Researchers at the EPSRC Centre have worked with ReNeuron to apply quality by design (QbD) methodology to cell culture and cryopreservation processes. By defining critical parameters and operating tolerances, better control of product development and production quality can be achieved.
Working with Neusentis, the team has developed a robust method for measuring cell viability after a cryopreservation process, defining improved cell banking and product thawing operations.
Our team has developed a novel, label-free, high resolution, multimodal light microscope that is capable of imaging sub-micron particles and the cellular membrane. The microscope can acquire sequential bright field and phase contrast images and uses a label-free approach to deliver video monitoring of live cells in higher resolution than has previously been possible, making this a viable method for quantitative in-process analysis.
The most recent project in the characterisation and control challenge looks at closed-loop control for improving cell culture processes when input and process variables require real-time adjustment to increase productivity. Using haematopoietic cells as an exemplar, researchers are developing a new non-immunological method of rapidly characterising haematopoietic cell populations to provide online monitoring of cells and the resolution between cell sub-populations necessary to implement an effective control loop in the process.
Collaborators’ testimonials
“Collaborating with Nottingham researchers within the EPSRC Centre is leading to the development of live and label-free cell imaging, which serves a long-term objective of providing industry with exploitable metrics of cell-biomaterial interactions.”
Dr Max Ryadnov, Principal Research Scientist, NPL
“In partnership with the Cell Therapy Catapult, the EPSRC Centre has accelerated ReNeuron’s manufacturing development work into scaled up and automated systems for a cell based regenerative product for phase III clinical trials and beyond.”
Dr Gary Brooke, Project Manager for Cell Manufacture and Development, ReNeuron
Key outputs
- Patent application pending for a novel, label-free, high resolution, multi-modal light microscope.
- EPSRC Career Acceleration Fellowship awarded to Melissa Mather, who co-invented the novel microscope.
- Success through industrial collaborations with Neusentis and ReNeuron on quality by design projects has led to a framework agreement on process development with the Cell Therapy Catapult.
- Key publications in journals including Journal of Biotechnology, Tissue Engineering, Biotechnology Letters and British Medical Bulletin.
Projects within the Characterisation and Control theme
- From science bench to the clinical application: Establishing a stem cell population with consistent therapeutic behaviours
- Non-invasive, label-free quantitative characterisation of live cells in monolayer culture
- Quality by Design (QbD) approach to risk reduction & optimisation of CTX (neural stem cell line) culture & cryopreservation manufacturing processes
- Quality By Design (QbD) approach to risk reduction and optimisation for cell therapy manufacture
- Selected-ion flow-tube mass spectrometry (SIFT-MS) monitoring of cell growth in CELL-tainer® bioreactor