Gene Therapy and Cell Therapy are new modalities of treatment and their production techniques at commercial scale create specific challenges.
Both therapies operate at a small scale, and extensively utilize single use technologies. At production scale, both processes require significant labor resources, and are not well controlled, so there is significant process variability. As companies gain experience, and as the processes evolve, this will result in better control and reduced process variability.
The challenge of gene therapy is the large scale production of a viral vector that contains, and can deliver, the gene of genes of interest to the patient. The overall process starts with growing cells, typically HEK cells, but then introducing the virus, and further growing the cells in a way that will produce more virus. The particular step for growing cells depends on whether the cells are adherent or can be grown in suspension cultures. The virus needs to be separated from the cells and purified through a sequence of steps into a final product.
There are many descriptions of the overall process, and here is a good example;
With gene therapy, one measure of the difficulty of commercialization is the dose required, measured in viral genomes (vg/ml). To manufacture a small number of doses, with a low titer is significantly easier than manufacturing large volumes of virus at high concentrations.
To accurately map the process at production scale is an essential step to commercializing the process.
With classic CAR-T cell therapy, as shown in the diagram below (copyright ACS), T-cells are removed from the patients body, but then boosted with an antigen to better recognize the tumor cell.
The overall process requires removing the cells from the patients body, modifying those cells, then growing them to higher cell numbers, before introducing them back into the patient.
We use process modeling to map the overall logistics and scheduling of this process, with focus on the multiplication process, which is a classic cell production process.