The process of creating an autologous therapy, from the collection of base cells through production and back to the waiting patient, has become increasingly complex.
This not because regulatory or other demands have intensified, but rather as we have gained more experience, we have discovered additional challenges that must be overcome to ensure success.
The therapy requires two separate cell collections from the patient—a tumor and a PBMC (apheresis) collection—and a process for the receipt, storage and distribution of the finished product.
Tumor cell collection - From a logistics perspective, the entire drug production process begins with the creation of a kit which will be used to collect the tumor and identify the tumor with the patient. This unique identification number is patient specific and will be used throughout the collection, manufacturing, distribution, and administration. This ID ensures the right drug is infused in the right patient. This kit will include a qualified shipper for transporting the tissue to an interim storage point. Using this kit, the tumor sample is collected and packaged for transport (via common carrier) to storage facility where it is received, inventoried and stored until ordered for manufacture. Once ordered, it will again be packaged in a qualified shipper and transported to the point of manufacture, where it is stored until manufacturing begins.
Apheresis collection - Timing and logistics are critical with regard to the apheresis collection, as the manufacturing process begins in earnest with the receipt of the dendritic cells. Unlike the tumor collection process, there is no interim storage step; however, as with the tumor collection, the process begins with a kit with all of the components required for an apheresis collection. The kit includes the patient-specific identification labels and collection containers as well as a qualified shipping container. The cells are shipped via carrier, with the addition of an important step—notification of the manufacturer that the shipment is on the way. The shipment is received by the manufacturer, the patient ID is confirmed, and the manufacturing process can begin.
Therapy returns to patient - Once manufactured, the dose or doses are cryopreserved and loaded into a qualified dry shipper for transport via common carrier to a distribution facility, where the material is received and inventoried. When the therapy is packaged to leave the manufacturing site, it is “acquired” for distribution to a patient. At the distribution center, the individual doses are inventoried and stored in vapor phase nitrogen until requested by a clinical/investigator site for patient use. Each requested dose is shipped in a qualified dry shipper by common carrier to the clinical site for administration.
While simplified, this three-step description gives a reasonable overview of the basic movement of the APCEDEN® and constituent materials required in an autologous manufacturing process. Now that we’ve defined the three processes.