The cell and gene therapy (CGT) industry has grown out of disparate groups of developers, suppliers, and service providers. Players in the sector must collaborate if we expect to commercialize new therapies at scale. Despite concerted efforts in the field, however, the critical question of how to automate CGT production has yet to be answered. Without automated processes in place, the sector risks spiraling costs and operational inefficiencies that could inhibit patient access to much-needed therapies.
Understanding such concerns, several institutions and companies â€” including my own â€” have joined the Cell and Gene Therapy Catapultâ€™s Process Analytic Technology (PAT) Consortium. It aims to increase efficiencies and lower overall production costs by assessing applications and combinations of multiple technologies for process analytics within CGT manufacturing. Currently, this is the largest global consortium in the CGT sector, with more than 20 member organizations (1).
Terumo Blood and Cell Technologies (BCT) is contributing automation technology and scientific knowledge to help the consortium accelerate process development activities. Specifically, we bring our Quantum cell-expansion system and expertise in culturing suspension-adapted targets, including T cells, viral vectors, and exosomes. The bioreactor at the heart of the closed, continuous, perfusion-based system uses hollow-fiber, semipermeable membrane technology.
Such technology is designed to eliminate labor- and time-intensive tasks because the ability to expand cells efficiently is critical during CGT production. But its greatest value for the biopharmaceutical industry lies in its potential for universal application. Participation in the consortium will help companies such as Terumo BCT to accelerate the development and adoption of automated solutions.
Our contribution is just one of many. Joining Terumo BCT and the Cell and Gene Therapy Catapult are Aber Instruments, Anthony Nolan, BD, Bio-Techne, Cambridge Consultants, ChemoMetec, C-CIT Sensors, Cytiva, Eppendorf, GlaxoSmithKline, Horiba, Imspex Diagnostics, Kaiser Optical Systems (an Endress+Hauser company), Ocean Insight, Ori Biotech, Oxford Nanoimaging, Quantex, See-Through, TeloNostiX, and Univercells Technologies. These members are exploring innovative solutions for process monitoring, including those for capacitance-based biomass monitoring and Raman spectroscopy. Such tools could facilitate data collection and analysis, providing real-time insights into CGT manufacturing processes.
To date, the consortium has worked to establish in-line sensor technologies and at- or off-line analytical technologies for suspension cell cultures performed in stirred-tank bioreactor systems. Consistent with the consortiumâ€™s focus on collaboration, results from those experiments are shared and discussed among member organizations. The next phase of this project will involve analysis of a commercially available stirred tank and the Quantum system, operated in parallel.
Terumo BCT also is providing scientific and engineering solutions for integrating on-line PATs with the Quantum system. The resulting sensor data could provide useful correlations to help optimize suspension-cell manufacturing processes. The work also will demonstrate promising capabilities that can come with integrating new PATs into CGT manufacturing.
The Future of CGT Manufacturing
While working with the consortium, we at Terumo seek to learn about newly available analytical technologies for CGT manufacturing and how they could be integrated with the Quantum system and other products in our portfolio. Such knowledge will be vital to the future development of technologies, software, and services for advanced therapies. In 2019, the former US Food and Drug Administration (FDA) commissioner Scott Gottlieb predicted that 10â€“20 CGTs would gain approval each year from 2025 onward (2). The PAT advancements and automation solutions being explored by the PAT Consortium will be critical to meeting upcoming manufacturing demands and addressing emerging financial needs. Even more important, access to such technologies will help to broaden possibilities for bringing life-changing therapies to patients.
1 Cell and Gene Therapy Catapult Brings Together Over 20 Organisations with the Aim to Accelerate Technology Development and Potentially Lower Cost in Cell and Gene Therapy Manufacturing. Cell and Gene Therapy Catapult: London, UK, 8 June 2021; https://ct.catapult.org.uk/news-media/general-news/press-release-cell-and-gene-therapy-catapult-brings-together-over-20.
2 Gottlieb S. Statement on New Policies to Advance Development of Safe and Effective Cell and Gene Therapies. US Food and Drug Administration: Silver Spring, MD, 15 January 2019; https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-peter-marks-md-phd-director-center-biologics.
Dalip Sethi, PhD, is director of scientific affairs at Terumo Blood and Cell Technologies, 10811 Collins Avenue, Lakewood, CO 80215; https://www.terumobct.com.