CGT Catapult and UCL to develop digital twin for CAR-T manufacturing

Cell and gene therapy (CGT) innovation and technology organization CGT Catapult has partnered with Stephen Goldrick, associate professor at University College London (UCL), to develop a digital twin using advanced process analytical technology (PAT) to improve chimeric antigen recaptor (CAR)-T manufacturing. The initiative supports the CGT Catapult’s goal of fostering collaboration among stakeholders for the greater advancement of the industry.

The partnership will specifically address challenges in determining the optimal conditions for cell expansion so that scientists will be better able to obtain viable, high-quality cells for advanced therapies.

The project uses data collected during a CGT Catapult PAT Consortium project that ran from 2021 to 2022. Stakeholders from throughout the industry contributed to that consortium, during which the CGT Catapult dedicated 28 of its scientists and subject matter experts to the project and its associated data-analysis work.

According to Marc-Olivier Baradez, head of data sciences at CGT Catapult, the organization is currently prototyping digital twins with the help of industry collaborators. After the new year, the team will seek to share outputs and demonstrate utility for what is an expanding class of therapy candidates.

“We will partner with therapy manufacturers and technology developers for deployment for commercial manufacture using the CGT Catapult multi-stakeholder environments,” Baradez told BioProcess Insider. That will enable accelerated deployment in a GMP setting. “This is likely to be stage gated, with perhaps manual interventions running alongside ‘twin’ interventions to build up and validate data sets and regulatory confidence.”

The promise of digital twins

The digital twin seeks to enable developers to identify and control optimal conditions for T-cell expansion, including nutrient levels and the timing for various process steps. Said Godrick, “This initiative aims to help us better understand this highly complex cellular system, focusing on how nutrient concentrations and environmental conditions affect cell growth and consumption rates.”

Baradez told us that “CAR-T manufacturing processes consist of several complex steps and numerous human interventions, adding risk to processes which need to be kept sterile.”

He added that the variability of patient-specific material and a lack of real-time analytics contribute to high failure rates. “By incorporating real-time monitoring, predictive analytics, dynamic process control and associated digital twins, the overall manufacturing consistency, reliability and throughput will improve, accelerating timelines and ensuring higher product quality.”

By supporting this initiative, the CGT Catapult anticipates improving manufacturing efficiency and quality predictability, enabling patients to receive treatments more quickly. “Digital twins will enable rapid optimization of manufacturing protocols through modelling and simulation, faster decision-making, reduced reliance on extensive manual monitoring, and action,” Baradez said. “Combined with the automation of manufacturing and analytical technologies, digital twins will facilitate the transition to streamlined and scaled CAR-T production whilst minimizing batch failure.”

“CAR-T products have changed the lives of many patients around the world and demonstrated the potential of cell therapies,” said Matthew Durdy, chief executive of the CGT Catapult. “There remain challenges in CAR-T manufacturing which need to be overcome to ensure that sufficient volumes of these therapies can be produced for the patients who need them. By working with Dr. Goldrick, an expert in digital bioprocess engineering, we hope to generate valuable data that could be used to more effectively manufacture high-quality CAR-T products.”

Baradez said his organization is committed to sharing technologies and discoveries through collaborative consortia, licensing models, and open-source access.

“The goal is to stimulate multidisciplinary stakeholders to advance the technologies, embed standards in its framework, and promote collaborative efforts to ultimately digitalize our industry,” Baradez said, before concluding, “Greater patient access to these life-saving therapies cannot be achieved at scale without such digitalization, and digital twins have a central role to play in this strategy.”