Pluripotent Stem Cell Scaleup

PSCs also have garnered much enthusiasm for their potential to provide advances such as for drug screening, disease modeling, and cellular therapies. However, PSC manufacturing scaleup remains a bottleneck.

Laboratory-scale PSC expansion strategies require costly complex media and regular handling by highly trained scientific personnel, noted Gary M. Pigeau, Ph.D., development manager, cell therapy, GE Healthcare. There has yet to be a demonstration of a truly scalable solution for PSC production.

Dr. Pigeau says that the industry needs to make some key changes: Cost-effective manufacturing of PSCs will require scalable suspension-based cultures; minimal (and xeno-free) medium formulations; and automated, closed, and integrated unit operations.

GE Healthcare is developing such solutions, according to Dr. Pigeau. The field is currently working at the 1 L scale, and a suitable solution to meet near- and long-term clinical requirements is needed, he explained. One of the primary challenges in scaling to larger volumes is the difference in vessel configurations, geometries, and mass transfer.

The GE Xcellerex portfolio of single-use, stirred-tank bioreactors is a scalable, modular platform spanning the 10 to 2,000 L range. The key in this scaling trajectory is the maintenance of vessel attributes, which enables the transfer of operating conditions across the product line. By demonstrating PSC expansion in the XDR-10 and beyond, we are intent on enabling the next generation of PSC-derived clinical trials.

Further, GE Healthcare is partnering with the Federal Economic Development Agency for Southern Ontario and the Centre for Commercialization of Regenerative Medicine (CCRM), a leader in developing and commercializing regenerative medicine technologies and cell and gene therapies, to build a Centre for Advanced Therapeutic Cell Technologies (CATCT) in Toronto. This initiative plans to BridGE the gap of industrialization for cellular and gene therapies.

The BridGE group is working toward developing the processes and products that will enable clinical trial sponsors to meet their manufacturing needs with respect to efficiency, scale, cost, and quality, reported Dr. Pigeau. We are currently executing on projects in the most active areas of cell and gene therapy to build and demonstrate our best-in-class solutions to manufacturing challenges in this emerging industry.

With respect to the PSC manufacturing initiative, the group recently demonstrated the production of 8 billion cells in one 8 L batch. These cells met our potency quality specifications throughout the manufacturing workflow and were successfully differentiated to high-quality cardiomyocytes, stated Dr. Pigeau. To my knowledge, this is the first successful PSC manufacturing endeavor at this scale. It represents a paradigm shift in modern medicine.

Excerpt from:
Streamlining Stem Cell Manufacturing - Genetic Engineering & Biotechnology News (press release)