Cold chain logistics can determine success or failure for any biotech company shipping time and/or temperature-sensitive products, many of which have the potential to save lives. These include traditional solid organs intended for transplantation into a recipient, and also a new and growing class of novel cellular therapies and engineered tissue products.
In the high-profile and promising personalized medicine arena, a circular process is used with cold chain logistics playing a critical part in two steps. For autologous cell therapies using chimeric antigen receptor and other types of T cells targeting various cancers, the process involves removing source material such as bone marrow, peripheral blood, or adipose tissue from a patient, shipping these to a processing and manufacturing facility, manufacturing a dose of therapeutic cells, and then shipping the cells back to the original clinical site for reinfusion into the same patient. Due to their fragile nature and limited shelf life outside the body, cold chain technologies are used to maintain a reduced temperature of these biologic materials, to slow or stop metabolic activity during transport.
Challenging the status quo in cold chain
Until recently, there has been minimal innovation in the design of insulated packaging systems used for the transport of time and temperature sensitive drugs, vaccines, biologics and other delicate life-saving materials. Traditionally, the industry has been rife with a lack of control, including gaping holes, interruptions and blind spots in processes, and the unavailability of temperature and other data to support the quality of a drug or cell sample. For example, the most commonly used insulated container in the healthcare industry is made from polystyrene (a beer cooler!); ice packs or some other temperature stabilizers are wedged inside to keep the product at a predetermined temperature but with no external monitoring capability. An aviation analogy can be used to illustrate critical assumptions and process limitations that exist in current distribution practices leading to sub-optimal conditions and potential disaster for patients. In retrospective investigations of aircraft disasters, typically a series of pilot errors are discovered; not a single decision, but a series of incorrect assumptions that build upon what preceded, leading to loss of life.
In the burgeoning regenerative medicine industry, when validating shipping lanes for prospective shipments of starting/source material and manufactured cell products, startup companies typically make three test shipments with temperature data loggers inside the shipping container. Upon receipt at the destination, the temp data is reviewed. If no temperature excursions occur during the test shipments, an assumption is made that none will ever occur during high volume commercial production, so often, no temperature data logger is included in every shipment—this is the first process deficiency—relying on a “validate then assume” mentality about the condition of transported biologic materials.
Next, even if a temperature monitor is included in each shipment, the data are not reviewed before the cells are administered to the patient. This is often completed days or weeks after infusion/injection, so the clinician is unaware of any temperature excursions that may have rendered the cells dead and useless. This is the second process deficiency. Lastly, since manufactured cells have limited shelf life, there is not enough time to aliquot a sample of cells from the received shipment to complete cell viability assays before dosing the patient. There is an assumption that the cells are viable. This is the third process deficiency. These process deficiencies create tremendous risk for patients, clinicians and providers since current distribution practices do not assure all stakeholders that time and temperature sensitive cells arrive alive and viable to provide their intended therapeutic benefit. The bottom line on this is that dead cells don’t cure cancer!
biologistex™ and evo™
To overcome these cold chain issues, BioLife Solutions and SAVSU Technologies formed the joint venture biologistex™ CCM. This is also the brand name of a cloud-hosted cold chain management Software as a Service (SaaS) that is integrated with evo™, a new generation of Smart Shippers designed by SAVSU and marketed by BioLife. The evo Smart Shipper product line perfectly complements BioLife’s family of proprietary clinical-grade cell and tissue hypothermic storage and cryopreservation freeze media products. To date, BioLife’s CryoStor® and HypoThermosol® are embedded into more than 230 customer validations and clinical trials of cell therapies targeting cancer, heart disease, vision loss, stroke, and other leading causes of disability and death. The combination of optimized, best-in-class biopreservation media and high-performance insulated shipping containers offer the cell therapy market a greatly improved chance for success in clinical trials, and hence regulatory approval to commence large-scale commercial production.
The evo Smart Shipper product line represents the next generation of cold chain packaging and logistics, empowering shippers to document the physical condition of their time-critical and temperature-sensitive shipments by incorporating multiple technologies. Weighing significantly less than comparably sized passive shippers, evo seamlessly integrates cellular communications with an onboard multi-parameter environmental, anti-pilfering, theft-deterrent monitoring system, a geo-location/geo-fencing feature and a secure, web-based app.
User-appointed designees anywhere in the world can monitor a package in near real time throughout its journey. The components are shaped so that they can’t be packed out incorrectly. A NIST-traceable thermocouple is embedded within the payload cavity, providing accurate payload temperature and eliminating the need for a separate data logger that can be accidentally discarded at the destination.
The biologistex Cold Chain Management Software as a Service (SaaS) app enables users to monitor high-value shipments during transit and configure actionable alerts for downstream recipients for location, approaching destination, delivery, package open, and remaining shelf life or ability via a countdown timer. These actionable alerts enable clinicians to improve patient logistics and ensure manufactured cell products are administered within their required shelf life.
Industry embracing new cold chain solutions
The benefits of using evo and biologistex for transporting a variety of temperature-sensitive products for research and clinical use is starting to gain recognition in the regenerative medicine and broader life sciences markets.
Vancouver, BC-based STEMCELL Technologies is currently testing the evo Smart Shipper and biologistex cold chain SaaS for potential adoption of these technologies into its distribution practices. Many of STEMCELL Technologies’ products, such as primary cells and cell lines are time and temperature sensitive, requiring cold chain logistics to ensure biologic stability and usability by end users. STEMCELL Technologies has been a strategic distributor of BioLife Solutions’ biopreservation media products since 2008.
Brooks Automation collaborated with BioLife Solutions and presented a poster on a shipping and storage study to support best distribution practices for T cells at the International Society for Cellular Therapy (ISCT) 2016 Annual Meeting.
In the study, current practices for cell freezing using a serum-containing home-brew freeze media and a common foam dry ice shipping container were compared to using serum-free, clinical-grade CryoStor freeze media and the CRYO evo dry ice Smart Shipper. Cells were frozen, shipped from BioLife to Brooks, transferred to liquid nitrogen storage for 45 days, then shipped back from Brooks to BioLife and assessed for viability and functional recovery. Significant improvement in total cell survival (viability) and faster regrowth (recovery) post-thaw were observed in the cells frozen in CryoStor and shipped in the CRYO evo Smart Shipper.
Among the specific findings of the study, Jurkat T-cells frozen in traditional 95/5% cryomedia and shipped in an EPS container experienced a significant decline in viability immediately post-thaw and a delayed return to function post-thaw. The combination of CryoStor and the evo Smart Shipper was observed to provide superior protection from cryopreservation and transportation stress with no measurable decline in functional viability as a result of freezing, thawing and two cross-country transit events.
Furthermore, the CRYO evo Smart Shipper and biologistex cloud-based shipment application allowed real-time status, tracking and event alarms to be sent throughout the entire shipping process, permitting enhanced tracking. The design of the CRYO evo Smart Shipper prevent payload warming from dry ice sublimation and maintained the Jurkat T-cells within the desired temperature range throughout transit.
Innovation in the design of the evo Smart Shipper and an IoT approach in the design of the biologistex Cold Chain SaaS have resulted in a complementary solution that enables shippers of time and temperature sensitive biologic materials to have better visibility of in-transit shipments, leading to better informed clinical decisions on the use of these materials with patients.
About the Author
Mike Rice is President and Chief Executive Officer of BioLife Solutions, a developer, manufacturer and marketer of biopreservation media products and smart shipping containers connected to a cloud hosted cold chain management app designed to improve the quality of delivery logistics for cells, tissues, and organs.