In October, scientists in Boston revealed they’d used genetically modified cells to cure 15 boys of a nerve disease that until now has been nearly 100 percent fatal. During a clinical trial, which lasted two years, doctors used experimental gene therapy to treat the boys with their own engineered cells. When the results came in, 15 of the 17 boys had no remaining disabilities.
Cell therapy uses living cells to treat diseases by helping them to recognize diseased cells or deliver a therapeutic cargo. Cells are taken from either a patient or a donor and modified in specialized manufacturing laboratories before being returned to the patient’s body. Manufacturing the cells is a costly and time-consuming endeavor. A single dose can cost hundreds of thousands of dollars to make.
That’s because in the more than 900 ongoing regenerative medicine trials worldwide — a 19 percent jump since 2016 — researchers generally manufacture each patient’s dose of bioengineered cells by hand. The individualized nature of cell therapy makes it not only prohibitively pricey, but also difficult to scale into commercial production. That hasn’t been a problem while cell therapy in the United States was still confined to research labs. But as medical science advances and increasing numbers of modified cell therapies are approved for general use, handcrafting doses will be too slow to scale. “It’s relatively easy to do 15 or 20 doses by hand, but it’s nearly impossible to efficiently make thousands,” says GE Healthcare’s Aaron Dulgar-Tulloch, director of cell therapy research and development at the Center for Advanced Therapeutic Cell Technologies (CATCT) in collaboration with the Centre for Commercialization of Regenerative Medicine (CCRM) in Toronto.
To help speed the process, Cellular Biomedicine Group Inc. (CBMG), a clinical-stage biopharmaceutical firm, is introducing high-tech industrial manufacturing to the field of cell and gene therapies. The company plans to install GE Healthcare’s FlexFactory in its Shanghai plant this year.
Above: GE Healthcare is working the Centre for Commercialization of Regenerative Medicine (CCRM) in Toronto to commercialize cell therapy. Top: As medical science advances and increasing numbers of modified cell therapies are approved for general use, handcrafting doses will be too slow to scale. Images credit: GE Healthcare.
FlexFactory for cell therapy is a closed, semi-automated system for manufacturing bioengineered cells. The system comprises a series of modules that link together what were formerly individual steps. Each FlexFactory is unique because it is custom-designed. FlexFactory is an end-to-end solution, designed with the equipment and process-development services that the customer needs to support manufacturing steps such as separating cell contents via centrifuge, freezing or thawing cells to preserve them, or harvesting the modified cells into a dose.
FlexFactory will make it faster, easier and cheaper to produce large quantities of cells to treat more patients. It is easier to install than traditional methods and can be operational in nine months, about half the time it would require a company to make a traditional lab ready for industrial-scale cell manufacturing.
CBMG decided the only way to make cell therapy commercially viable was to bring down the cost, and FlexFactory is one way to do that. “If the price is too high and no one can afford it, cell therapy is not practical,” says Tony (Bizuo) Liu, CBMG’s chief executive officer.
CBMG will be the first company to install FlexFactory for cell therapy in its facility, and will use it to create cell therapies to treat various blood and solid tumor cancers. It should be up and running by the end of the year.
Manufacturing bioengineered cells is a delicate, multistep process that requires specific modifications to the cells at specified times over the course of hours or days. Every time a researcher works on the cells — say moving them from a sterile cabinet to a centrifuge or adding new genetic material — there’s a chance of contamination or error that could destroy the cell-based therapy.
But with FlexFactory, the cells are in a sterile, closed system, and because many modifications are done through semi-automated steps, the process is more precise and standard. The automation leads to faster production compared with traditional small-scale manufacturing methods.
The quick installation and reliable processes mean cell therapies could be cheaper to manufacture, scaled more easily and delivered to more patients sooner, Dulgar-Tulloch says. “FlexFactory for cell therapy allows a company to manufacture multiple (doses) for multiple, unique patients at a faster speed,” he says.