This past August, the FDA approved the first chimeric antigen receptor T cell (CAR-T) immunotherapy, Novartis’ Kymriah for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL). It uses specifically developed Cell Therapy Systems (CTS) Dynabeads technology, part of Thermo Fisher’s  CTS portfolio. The magnetic beads isolate, activate and expand T cells that have been genetically engineered to recognize and fight cancer cells in each individual patient.
 
Recently, Kite Pharma received approval from the FDA for Yescarta, a CAR T therapy for the treatment of relapsed or refractory large B-cell lymphoma. Kite, headquartered in Santa Monica, CA, was recently acquired by Gilead for approximately $11.9 billion.
 
Cryoport, a provider of cold chain logistics for temperature-sensitive life sciences materials, is the logistics shipper for both of these products, which represent the first two commercialized CAR-T cell therapies now available for patients. Jerrell Shelton, Cryoport’s chief executive officer discusses the processes and technologies associated with supporting logistics for CAR-T therapies. –KB
 
 
Contract Pharma: What services are involved under the contracts with Novartis and Kite?
 
Jerrell Shelton: Cryoport provides comprehensive and tailored cold chain logistics solutions to both Novartis and Gilead’s Kite Pharma in support of their respective clinical trials and the launching of their respective first commercial CAR T therapies, Novartis’ Kymriah and Kite’s Yescarta. We have multi-year Master Service Agreements in place and both agreements are subject to strict non-disclosure clauses which preclude us from going into details.
 
What we can say is that in both cases of these first CAR-T therapies approved by the FDA, Gilead’s Yescarta and Novartis’ Kymriah, is that they are supported by Cryoport’s advanced logistics solutions, which includes primary and secondary packaging, informatics, and logistics expertise. Cryoport also supports other therapy developments in both Gilead’s and Novartis’ clinical pipeline with our technology-centric cold chain solutions.
 
These ground-breaking regenerative therapies are manufactured by different companies, with different indications and, therefore, have separate protocols, which Cryoport supports with its cold chain logistics solutions specifically tailored to these novel therapies.
 
CP: Please describe the logistics process for CAR-T cell therapies and other regenerative medical research samples.
 
JS: Cryoport’s logistics solutions are developed to serve the entire range of cellular therapies. Immunotherapies are the area that is currently developing most rapidly, that does not preclude very interesting developments in other areas such as B-cells and antibodies.
 
The currently approved CAR T-cell therapies are autologous, which means that the treatment is personalized for the specific patient. A blood draw is taken from the patient’s body. In the process, the blood is then passed through an apparatus, specified by the biopharma manufacturer that separates the blood into plasma and cells and returns the remainder to the patient’s circulation.
 
These draws from the patient’s blood are then shipped via Cryoport Express Shippers, either cryogenically (-196°C) or at chilled temperature (2 to 8°C), to the biopharma manufacturer for processing where, in the case of CAR T-cells, the T cells are married to a chimeric antigen receptor making the T cells into CAR T-cells for the purpose of boosting the patient’s own immune system to target and eradicate the targeted cancer.
 
Once the CAR T-therapy is produced, its temperature is brought down to cryogenic conditions, that is, -196° Celcius, and then shipped, by Cryoport’s technology logistics services using Cryoport Express Shippers, which include our SmartPak II Condition Monitoring System, to the point of care designated by the biopharma manufacturer. A controlled thaw of the cryogenically frozen therapy then takes place and the patient is inoculated with his/her CAR T-cell therapy.
 
It is an amazing process that holds great promise for the betterment of mankind and healthcare. We are in the early days of a transformation in the practice of medicine and cures for heretofore incurable conditions and our Cryoport team feels honored to be able to play such a vital role in moving this transformation forward. As one scientist said to me recently, “The therapy is half the battle; the other half is the logistics.” Cryoport is happy to serve in this strategic role.
 
CP: What are the current logistics challenges for CAR-T cell therapies and how can they be resolved?
 
JS: Providing high quality, technologically-advanced and reliable solutions in support of this fast-growing regenerative medicine market is not only critical to Cryoport’s success but to the success of our clients and the market at large.We take this responsibility very seriously. We receive advice from NASA engineers as well have the finest engineers in the world, the most advanced information technology specialists in the life sciences, enabling us to have advanced logistics competenciesincluding: real time condition monitoring, cloud-based logistics software platform, intervention capability and expertise.
 
CP: Are there potential limitations expanding access to CAR-T therapies as more therapies are approved?
 
I can only speak to the logistics side of this, but put simply, there are none. Our strategy is modular and flexible, allowing us to tailor our solutions to meet individual client demands. We are innovating constantly; there is no scientific, engineering or process problem that we see on the horizon, that we cannot handle.
 
 
CP: How do technology solutions play into various stages of cell therapy development, manufacture and delivery processes?
 
Cellular therapy in the Biopharma market begins with research and then advances to clinical trials and then to commercialization. Cryoport plays a vital role at each stage of development as each therapy requires dependable temperature controlled logistics solutions. To accomplish this, we work from three complements of “tool sets”: packaging, information technology, and logistics expertise.
 
Our complex packaging is an assembly, and our packaging design employs packaging engineering, mechanical engineering, materials engineering, electronics engineering, informatics and the workings of the physics of liquid nitrogen. We call these primary packaging units, Cryoport Express Shippers. Each of the shippers are composed of components including an outer shell, dewar flask, thermocouple, sensors, and a real-time condition monitoring system we have branded as the SmartPak II Condition Monitoring System. We communicate with our Cryoport Express Shippers on a real-time basis, polling each unit as frequently as every five minutes to monitor the conditions in which the therapies reside. We not only monitor the internal conditions, we monitor the external conditions. We always record the Chain of Custody and the Chain of Condition as any temperature excursion can compromise efficacy, rendering the cellular therapy useless.
 
All the communication and data storage is enabled by the Cryoportal Operating Management Platform, a logistics management platform serving the life sciences. The Cryoportal actually starts our processes beginning with order entry, where it records vital information and produces all paperwork, including customs documentation for over 100 countries; it assists in order fulfillment and monitoring as it interfaces with the SmartPak II.
 
As you can see, Cryoport is very much a technology-centric company with solutions that are designed to be tailored to the specific needs of our life sciences clients at each stage of the development cycles of their products.
 
We support three distinct markets within the life sciences: Biopharma; Animal Health and Reproductive Medicine. Cellular therapies are being developed predominantly in the Biopharma market, however we have also started supporting cellular therapy development initiatives in the Animal Health market.
 

Shelton of Cryoport