The advent of personalized medicine has ushered in a new era for healthcare and brought hope for patients facing rare diseases and previously untreatable cancers. Cell and gene therapies (CGT) represent a confluence of medical research and scientific technology decades in the making that has grown into a revolution in patient treatment. These living medicines present a logistical challenge unlike anything previously seen in the pharmaceutical industry. Unlike traditional shelf-stable drugs, CGT’s are often patient specific, irreplaceable and highly sensitive to manufacturing- and supply chain-related disruptions.
For life science companies, the stakes are high for ensuring these delicate lifesaving drugs make it to the patient at maximum efficacy. A successful delivery means a new lease on life for a patient, but conversely, a logistical failure means the loss of a unique, life-saving treatment and indeed, even potential loss of life if a catastrophic failure were to occur. The collateral damage in the event of a failure is also often underestimated - patients may need to be rescheduled, undergo lengthy procedures such as leukapheresis or preconditioning therapy, or incur additional costs to fly or drive to hospitals and manufacturers need to recreate the highly bespoke treatment from scratch when a CGT is lost or damaged. In this high-stakes environment, standard freight solutions are no longer sufficient. Specialized logistics, delivered by qualified individuals and defined by uncompromising precision and agility, is the only path forward.
The race against time: Strict requirements and technological response
CGTs often have an incredibly narrow stability window in terms of cell viability, as well as packaging validation. Whether derived from autologous or allogeneic processes, the shipment of raw materials (e.g. leukapheresis, lentiviral vectors, cytokines, media) or final drug products (e.g. cryopreservd CAR-T cells), demands flawless execution. Visibility into critical data is imperative and being nimble and adapting during a disruption is paramount. In many cases, the delivery window may be as short as 30 minutes due to the strict requirements for patients' dosing and preconditioning. Certain therapies also require cryogenic storage and transportation solutions maintained at temperatures below -150°C using liquid nitrogen (LN2) vapor shippers -- allowing for cryopreserved cells to be safely transported while maintaining cell viability, quality, phenotype and function. However, this adds complexity to the logistics due to the packaging that must be used, such as more weight, larger dimensions and a risk of being rejected due to incorrect labelling. Not to mention, LN2-packaging requires testing, validation and filling/conditioning often days in advance, to ensure the shipper is suitable for use.
Marken’s logistics framework remains agnostic to packaging and data loggers, such as temperature and GPS sensors, allowing a higher degree of agility when using cutting-edge monitoring and packaging to assist in monitoring temperature integrity and routing. We implement strict time-definite protocols, treating every shipment with priority to ensure that the biological activity of the cells remains uncompromised from the lab to the clinic.
In the CGT world, knowing where a shipment is may not be sufficient in and of itself. Marken’s 24/7 CGT control towers are designed for team members to watch shipments in real time, using a combination of data logger technology to monitor internal temperature, light exposure, tilt and shock, while also leveraging tribal knowledge and speaking directly with drivers or clients to ensure exceptions are handled and escalated proactively. This data is available in near real-time via live-view-link (LVL) software, allowing our teams to intervene before any deviation has patient impact.
Empowered by the skies with dedicated air lanes
Commercial aviation exposes critical flights to many variables, like mechanical delays, rigid schedules and airspace congestion, which could impede the shipment. When transporting a starting material or a final C&G therapy with a 48-hour shelf life, waiting for the next flight out on a commercial airplane that prioritizes passengers over life-saving cargo is not an option. To mitigate these risks, Marken provides dedicated flight solutions through various resources.
As part of the UPS family, Marken often draws on the strength of the UPS air fleet to allow for more control over the flight path, departure times and tarmac handling procedures. Likewise, we have dedicated aircraft and other options including onboard carry and charter solutions inside our network ready to respond to immediate needs with expertise capable of carrying high-value, ultrasensitive shipments.
This eliminates the risk of shipments being bumped due to overbooking and allows for direct flights to secondary airports closest to the final treatment center, drastically reducing ground transit time. Commercial flight options unfortunately cannot match the unparalleled control and adaptability of an owned fleet of aircraft – this ensures life-saving therapies reach their destinations on time and in specification, every time.
Reaching the unreachable: Remote areas, regional hazards and global access
Clinical trials and access to CGTs are increasingly global, often seeking to reach patients in remote or rarely accessed regions where a fully developed infrastructure is unavailable. As these treatments grow in popularity and their safety profile is better understood and managed on an outpatient basis, we find more community hospitals and the rural clinics administering them. The major hospitals no longer have capacity to treat more patients in the advanced therapy space, thus enabling opportunities to reach patients in rural areas that require an even more white glove approach to ensuring the therapies can be shepherded to patients in critical need.
In one recent example, CGT shipments to southern Italy fell into a strict time window and required unique packaging. For this area, special courier expertise is necessary for overcoming a challenging ground journey to local hospitals in the countryside on the island of Sicily. Given the exacting timeline and treacherous driving conditions, Marken continuously hones contingencies and protocols to streamline shipments through complex geographies to deliver life-saving medicines in rural areas. Leveraging a vetted network of local specialty couriers who understand the nuances of last-mile delivery in this area, as well as experts who understand the delicate nature of the therapy, ensures the cold chain remains unbroken even in the most challenging geography.
Logistics excellence endures the most severe tests through external disruption and the current geopolitical landscape in the Middle East also has demonstrated that a complex web, composed of closed airspaces, sudden regulatory shifts and heightened security protocols, is now the new norm in all war-torn regions. For CGT manufacturers, these disruptors threaten the viability of entire regional clinical programs. This hasn’t been insurmountable for Marken’s Advanced Therapy Logistics division, which navigates regional closures with reliable lane mapping and dedicated flights for shipments, as well as knowledgeable, established drivers and robust contingency planning.
Consider Marken’s deft response to recent shipment of apheresis leaving two patients in Israel. On the daily update call the Marken CGT team had routinely held for months, a client mentioned an apheresis shipment dropped by another carrier. After several calls within the UPS network and an assessment of customs requirements, the shipment was back on track within a couple hours and on its way to the manufacturer in the EU. Even with the challenges surrounding Israel and the Middle East, Marken CGT operations was able to get the shipment moving again and provide hyper care updates while navigating regional disruption.
These instances illustrate Marken’s 24/7 risk management and the relentless drive to deliver what matters to patients in need. When a first round of options is exhausted, layers of pre-planned alternative routes were put into action, utilizing strategic gateways in Europe, Africa and Asia to bypass closed airspace when necessary. Deep relationships with civil aviation authorities and other stakeholders help expedite documentation and prioritize regulatory clearances, ensuring life-saving therapies do not experience delays.
A partnership of trust
The highest caliber of precision in logistics is necessary to advance the field of CGTs. It is far from simply an administrative function; it is a clinical necessity. With the technology and network capabilities, operations teams control shipments relying on pilots and couriers who physically handle and transport the package, demanding a team of professionals to oversee each aspect of every CGT shipment. Our mission provides the infrastructure to allow lifesaving, hypersensitive medicines to reach the patients who need them most anywhere in the world. Through a combination of dedicated air freight, real-time monitoring and expert crisis management, we ensure that the future of medicine is never left to chance.
