My previous eBook, Commercially Successful Cell Therapies: Navigating the Ultra Cold Chain Distribution Minefield, and several of my blogs, have discussed the basics of building a successful logistics strategy for the management of cell-based material. If you read these, then you are aware of the better-known and important factors to consider, such as:
- Selecting the right dry shipper
- Qualifying that shipper to the particular payload and shipping configuration
- Choosing an appropriate data logger
- Creating a chain of custody
- Evaluating a transit carrier
- Anticipating potential problems inherent in shipping at cryogenic temperatures
This eBook goes beyond the basics and acquaints you with some of the lesser known considerations. Although they may be hidden in the background, these factors can play a major role in the success or failure of a clinical trial and the long term efficacy of a cell-based commercial product. They are:
- Package and shipping qualification
- Equipment validation
- Process qualification
- Documenting the chain of custody
I am focusing this eBook on the unique logistical challenges of autologous cell-based therapies, that is, therapies that use a patient’s own cells for the manufacture of a treatment that is then administered only to that patient. The other type of cell-based therapy is referred to as“allogeneic” and is derived from an unrelated donor or donors, and administered to the relevant population of patients. All of the considerations I mentioned above apply to allogeneic as well as autologous therapies.The Unique Complexity of an Autologous Therapy
First, let’s map out the multiple paths traveled by the various entities that must come together seamlessly for an autologous cell therapy product to be successful.
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. As a point of reference through this book I will use the flow chart below to illustrate where in the chain of custody these challenges occur and need to be addressed.
This chart represents a fairly typical process chain for a cancer-related autologous cell therapy. The therapy requires two separate cell collections from the patient—a tumor and a dendritic cell (apheresis) collection—and a process for the receipt, storage and distribution of the finished product. Let’s take a moment to define this chain in greater depth by looking at the three high level processes detailed in the chart.
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 common 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 and begins the journey of a drug 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 drug and constituent materials required in an autologous drug manufacturing process. Now that we’ve defined the three high level processes, let’s look at the additional considerations mentioned earlier and their impact on the success or failure of a cell-based therapy.
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