Recently, Charles River Laboratories—a provider of products and services for drug research and development—presented a webinar about starting material for manufacturing cell therapies.
Scott R. Burger, MD, founder of Advanced Cell & Gene Therapy in Chapel Hill, NC, kicked off the webinar with this mantra: “Good beginnings make for good endings.” Nonetheless, he noted that the starting material for cell-based products involves many challenges, including its complexity, variability, and the impact of environmental conditions.
The source of the starting material also determines the required safety testing, which is governed by regulatory agencies, including the FDA. For example, after expanding induced allogeneic pluripotent stem cells (iPSCs), which are taken from multiple donors, a manufacturer must perform regular safety testing of the master cell bank and the working cell bank. When the starting material comes from expanding primary allogeneic cells, the cells must be tested for sterility, mycoplasma, and endotoxins. Other sources of starting material require specific forms of safety testing when manufacturing a cell-based therapy.
When Matt Hewitt, PhD, senior director, scientific solutions, cell & gene therapy at Charles River in Wilmington, MA, took over the webinar, he reiterated that “starting material is certainly the first influential step within the manufacturing journey,” and it “impacts all of the downstream operations that come after it.”
Beyond being available, the starting material for manufacturing a cell-based therapy must be of consistent quality. Otherwise, all of the downstream steps become more complicated, Hewitt explained.
When collecting cells from donors to make cell-based therapies, variability is inherent in the samples. Still, Hewitt and his colleagues try to minimize this variability in several ways, such as having pools of donors that can be reused as needed. Nonetheless, even samples from the same donor can vary, such as including different numbers of white blood cells over time.
After collecting a sample, keeping the cells fresh or cryopreserving them impacts the cells in different ways. For instance, cryopreservation increases the stability of the cells over time and makes them more readily available for manufacturing, Hewitt pointed out. To maintain viability with cryopreservation, though, the freeze and thaw cycles must be carefully and consistently controlled to prevent problems, such as the formation of ice crystals.
As the information presented in this webinar showed, the manufacturing of cell therapies follows a key mantra of computing: garbage in, garbage out.
