Vector suppliers need better ways of growing adherent cells, according to the team behind a new single-use culturing platform, who say current technologies are not suited to industrial-scale production.
Adherent cells—which grow attached to surfaces rather than in suspension—are vital for biopharma. For example, some 70% of the viral vectors used in cell and gene therapy development are produced using adherent cells.
Luxturna, the retinal disease therapy, uses a delivery vector made in adherent HEK 293 cells cultured in a 2D roller bottle. Likewise, the spinal muscular atrophy (SMA) treatment, Zolgensma, uses vectors made in the same cell line grown in a fixed-bed bioreactor.
Scale-up issues
The reliance on adherent cells has become a problem according to Joel Eichmann, Dr. rer. nat., of Germany-based tech developer, Green Elephant Biotech, who says current culturing technologies are difficult to scale.
“When scaling up a process based on adherent cells, a biopharmaceutical manufacturer has two options. Either stay in 2D, resulting in the use of heavy and difficult-to-handle multi-tray stacks with a large footprint, requiring a lot of manual labor and driving up COGS.
“The other option is to take the time to develop a 3D process, which requires a high investment in process development and carries the risk of not meeting product specifications due to unintended cell differentiation or altered post-translational modifications of the product,” he told GEN.
With this in mind, Green Elephant developed CellScrew, which it describes as a scalable, dynamic cell culture system.
“It can be used as a stand-alone system for early stages with no equipment CAPEX and can be equipped with sensors and automated for later stages without changing the environment for the cells. This reduces the time-to-market and COGS of biopharmaceutical products, particularly in cell and gene therapies where manufacturing is the key bottleneck to patient access,” Eichmann says.
“The large surface area is a key aspect, especially when combined with the compact design of the flask. In the footprint of a standard roller bottle, the CellScrew offers a surface area of 10,000 cm2, which represents a 12-fold process intensification.
The technology has been on the market as a research-only product for about two years, however, recently Green Elephant teamed with Bürkert Fluid Control Systems to develop it for the commercial market.
“Together with Bürkert, we will transform it into a fully integrated and automated system for adherent cell processes, monitoring and controlling a wide range of process parameters such as pH, metabolites, gases, and pressure.
He added, “This collaboration combines Bürkert’s expertise in fluid and gas control and system integration with Green Elephant Biotech’s expertise in adherent cell processes and sustainable single-use solutions. The result is a platform that combines the best of both 2D cell culture and bioreactor worlds, reducing manual handling time per batch from hours to minutes and increasing process robustness and reliability.”