Understanding the Cellular Therapy Supply Chain
Cellular therapy products offer the promise of a cure to patients that have failed traditional cancer therapies as well as to patients suffering from genetic disorders. Many of these products are manufactured from “autologous cells” derived from the patient or alternatively from “allogeneic cells” derived from a different donor. The sequence of processes involved in the production and distribution of cellular therapies is referred to as the “supply chain.” Each step in the supply chain must be carefully controlled and monitored to maintain the viability of the cells and the resultant product and to ensure that the cellular product is safe and effective for patients. Steps include:
- Procurement of cells from patients or normal donors
- Storage and/or transport of these cells under temperature controlled conditions to the manufacturing facility
- Manufacture of the cellular therapy product, storage of the product under temperature controlled conditions until the patient is ready for treatment
- Distribution of the product under temperature controlled conditions to the patient
- And finally Treatment of the patient
Most cellular therapies develop from ideas and experiments, designed to test these ideas, performed in research laboratories in academic or pharmaceutical company settings. Generally, during development, experiments are performed on a small scale with cells obtained from generous donors who provide their cells even though they themselves may not derive any benefit from the experiments. Once the pre-clinical experiments provide evidence that the cellular product may be effective, the investigator must determine how to manufacture products under standard conditions for multiple patients and how to safely store and deliver these products to each patient.
Contract manufacturing laboratories are often employed to “scale up” production of manufacturing for clinical trials and ultimately to commercial products and thus play an integral role in the supply chain. Immune cells like lymphocytes and stem cells for some genetic therapies can be collected from blood by a process called apheresis. During apheresis collection the donor’s blood passes through a machine and some white blood cells are removed and the remainder of the blood is returned to the donor. The product’s collection is labeled with multiple unique identifiers, including bar codes. The same identifiers are used to label and identify the products at each step of transport, storage, manufacture, and administration, to ensure that the correct product is returned to the correct patient.
Once the cells are collected they may be processed and cryopreserved to maintain their viability while they are transported to the manufacturing facility. The transport occurs under standard conditions at specific temperatures. Once the cellsarrive at the manufacturing facility they may once again be stored under standard temperature conditions known to maintain their viability until the manufacturing process occurs.
Manufacturing is complex, involving coordination of many steps, reagents, supplies, and types of equipment. Good manufacturing procedures (GMP) are used to ensure that the product is manufactured the same way for each patient. When autologous cells are used, the patient’s medical condition may seriously affect the ability of the cells to reach required potency. Similarly, reagents and other supplies must be standardized, and manufacturers of these items must be able to provide uninterrupted availability. This can be difficult if suppliers of these materials have production problems resulting in shortages.
Once the cellular product is manufactured it is again stored and transported under controlled temperature conditions for to the facility where the patient will be treated. The supply chain loop is completed when the product and patient identities are confirmed, and the product/treatment is administered to the patient. In an era of efficiency, companies should not have to establish multiple sources, and ensure GMP capabilities of vendors as it is time consuming and costly. Instead, they should be relying on organizations that have the expertise and experience in every step of the workflow, including the ability to acquire FDA approval.