In initial phases of development, the focus is on finding a way to obtain the desired cells, with cost being less of a driver. However, on a larger scale, cost becomes a significant issue, and creates the need for alternative manufacturing technology to be implemented. It is also important that emphasis remains on the safety and reproducibility of the process, as well as adherence to GMP standards.
When growing adherent stem cells, a surface must be provided. In the laboratory, this is relatively simple, and there are several systems available. Flasks and multiplate stacks allow adherent stem cells to grow successfully on a two-dimensional (2D) surface. However, problems appear when the product moves into the later stages of clinical trials and larger numbers of cells are required. It must be noted that there is a difference between the processes for autologous and allogeneic therapies. For an autologous therapy—one based on the patient's own stem cells—the batches remain the same size, but many more batches are required, so scale-out is needed. However, for an allogeneic therapy, where all patients receive the same cells, the batches become much larger, and the process must be scaled up, so a much larger surface area is required.