Industry Experts Find Creative Solutions To Optimize Cold Chain Logistics
By Life Science Connect Editorial Staff
Cell therapies have progressed dramatically in recent years, but the cold chain infrastructure that supports them is lagging behind the science of advanced medicine. Cryopreservation, storage, and shipment options are much the same as they were 10 years ago. However, systems for monitoring and recording shipping and storage have improved significantly.
Cell & Gene’s chief editor, Erin Harris, sat down with Ryan Crisman, cofounder and CTO at Umoja Biopharma, and Rookie Gleich, global head of cell therapy logistics and shipping systems at Bristol Myers Squibb (BMS), for Optimizing Your Cold Chain For Cell Therapies. Crisman and Gleich shared how they’re improving their shipping systems, cryogenic preservation, courier selection, and team building to ensure that their products remain viable and are fully traceable on the journey from manufacturing facilities to hospitals and clinics and, finally, to patients.
Planning For Success
"Curing patients with their cells is a fascinating field, but when I started Umoja, I asked how we can go from a single patient and single product supply chain to reaping the benefits of cell therapy with the logistical opportunities that we see with small molecules and monoclonal antibodies," stated Crisman. "And so Umoja looked at solving that supply chain and accessibility challenge by using biology."
Crisman explained that instead of approaching the problem as a single-patient, single-product challenge, his company created one lentiviral manufacturing run to treat thousands of patients with a single process. They made a direct injection of the lentiviral particles that allow patients' bodies to create the CAR T cells. The lentiviral drug product is sent to clinical sites and infused into patients when needed.
Gleich agreed that when companies begin their drug development process with manufacturing and shipping logistics in mind, they set themselves up for success. When clinical trials begin, most companies are focused on creating something that works in a lab and aren't considering their commercial needs down the line, such as the logistics of creating and distributing thousands of treatments for patients.
"Don't start with a process defined by the shipping container," explained Gleich. "Start with a process that defines the material and test the material first to understand the outer edges of the acceptable temperature range, giving you more flexibility with shipping. It's a big learning curve, but my work at BMS focuses on testing and finding starting materials that give us flexibility across the available shippers for specific temperature ranges."
Crisman added that with advanced therapeutics, the colder the storage temperature requirements, the greater the costs and the bigger the need for an advanced infrastructure. Therefore, couriers must have the experience and capabilities necessary to solve problems as they arise, such as being able to restock dry ice in transit to prevent emergencies. Likewise, having backup systems along the entire supply chain is essential.
"Everything that can go wrong will go wrong at some point," Crisman explained. "So, it's critical to have backups in place. One or two points of failure aren't sufficient because the supply chain has too many touchpoints. Having as much redundancy as possible helps you sleep better at night."
Managing Cryogenics Logistics
"Rookie is right that when designing first-in-human platforms, you should have a commercial mindset from the start," stated Crisman. "From a materials perspective, you should find redundancies in raw materials that you can use to show that you don't have single source requirements up front, including what you need for cryopreservation.”
According to Crisman, cryogenic logistics are a crucial but often underexplored element of cell therapy commercialization. He explained that therapeutics are often frozen on-site in academic settings without closely examining the effects of temperature variations on the cells. But for commercial production, companies need to study the cryogenic process closely using controlled rate freezers to demonstrate how freezing and thawing affect the cells. In a commercial setting, deviations throughout the process impact on a larger scale than in preclinical or clinical settings. Understanding the temperature range at which the drug can be safely delivered to patients is crucial, and this influences shipping logistics. Crisman added that new technologies are emerging that track the drug's temperature in real time, but they are yet to be widely adopted.
Gleich commented that cryogenic systems are easy to manage and provide flexibility but are expensive. The more products or material that need to be preserved cryogenically and shipped, the higher the costs. Also, extracting the drug from its cryopreservation involves specialized equipment and can be challenging to manage. Cryopreservation also involves large storage tanks, which take up valuable space in hospitals or clinics and raise chain-of-custody concerns. Smaller vessels are more user-friendly but hold less product, further driving up costs. Meanwhile, liquid nitrogen is ideal for cold storage but has limited suppliers, while dry ice is less expensive but difficult to control because it evaporates quickly, leading to temperature variations.
"Again, finding the right temperature for your material and product is crucial, but you must also be aware of the supply chain offerings available for those temperature ranges and understand the positives and negatives of the various shipping systems," Gleich explained. “There are many options out there, and although liquid nitrogen is bulky and difficult to ship, it’s often the thing that keeps your product the safest when ultra-cold temperatures are required.”
Choosing The Right Courier
Crisman added that timing is everything in cold chain logistics, and reducing time in transit is highly advantageous. Companies must consider everything that could go wrong in the shipping process and have risk mitigation plans. Creating redundancies in temperature tracking and using tools like GPS trackers help validate the product's viability. Companies benefit by building a buffer window so that shipping or drug delivery delays don't destroy valuable therapeutics.
"Thoroughly vet your shipping partners," Crisman advised. "Early clinical-stage companies may want to go with the most cost-effective option, but a lot of times, the less expensive shipping companies are smaller and rely on larger companies for their air cargo fleets. That creates more opportunities for delays. Companies should weigh the risks of taking a chance on smaller, less expensive options or paying more to the bigger entities that offer more stability."
Gleich added that the downside to white-glove courier services is that it's difficult to scale up to commercial quantities. Large companies like FedEx or UPS use centralized shipping centers that don't have the flexibility of smaller couriers, who can handle customized, time-bound shipments. Gleich foresees improved systems with bar code scanning at critical points to create greater accountability and real-time data. Also, BMS is looking into incorporating AI machine learning to look at schedules, access cloud-based GPS and other data, and create proactive notifications for potential problems so that companies can focus their energy on the shipments that need intervention without manually tracking every package.
"When you're talking about a patient's life, every autologous lifesaving therapy is important, and a 99% success rate in transportation isn't good enough because that one person out of a hundred didn't get their treatment," Gleich elaborated. "So, we're always striving for 100% successful delivery because the patients are the most important reason we do what we do."
The challenge, Gleich explained, is creating a scalable supply chain to meet patient demand. One solution is building in diverse redundancies so that a backup supplier is ready to go if one supplier fails. Another solution is having multiple suppliers and systems that allow BMS to handle unknown obstacles along the way. As a large company, BMS can choose the best-in-class shipping and courier options. Still, he expects demand for new therapeutics such as CAR T, allogenic, autologous, and radioligands to grow and compete with those leading couriers, taxing their capacity.
“If every company with innovative trials suddenly got their drug approved, we’d see a huge gap in the ability to service all of them, and cold chain logistics would see a significant bottleneck,” Gleich illustrated. “Therefore, building relationships with the best suppliers now is critical to future long-term success.”
Engage The Entire Supply Chain
Having the right logistics team with diverse skills and experience is also essential to success. Crisman recommends cross-training team members responsible for scheduling, staging the shipments, and providing shipment validation studies rather than siloing their roles. Educating the entire team on what's being shipped, how, and what technologies are keeping the material cold allows them to start innovating and finding creative solutions. Hiring people with diverse backgrounds encourages them to find new opportunities to improve the process.
"Training is not just your internal team," Gleich added. "Every person along the supply chain should understand that these drugs are impacting patients' lives and that we must maintain a chain of custody, precise temperatures, and deliver the drug on time because a patient depends on it. We've met with cargo airline crews and asked them if they knew someone with cancer and, of course, most people have. When we explained to them that these boxes contain drugs that treat cancer, it hits home. When your entire supply chain understands the importance of what they're handling with every box that comes their way, you have a better chance of that box getting where it needs to go, on time."