The time-sensitive, temperature-sensitive supply chain for cell-and-gene therapies (CGT) requires a highly coordinated, highly choreographed dance under the best of circumstances. Against the backdrop of the global COVID-19 pandemic, 2020 is creating anything but the best of circumstances.

COVID-19 emerged quickly but now defines the landscape throughout the pharmaceutical industry and is creating unique challenges throughout the CGT arena. In particular, COVID-related issues are creating disruptions in three particular areas of the complex CGT manufacturing and care-delivery model:

• By creating health risks and obstacles for how patients and clinics are able to carry out their normal procedures and protocols. This makes it harder to reliably collect blood and stem cells from patients and third-party donors in the upstream clinical setting, and to administer the resulting manufactured CGT therapies to the immunocompromised patients who are eagerly awaiting them in the downstream portion of the process
• By creating delays, interruptions and other complications in transportation and delivery, throughout the tightly controlled cold chain that is utterly essential to safeguard and maintain the integrity of the biological source materials and lifesaving bioengineered CGTs at every step of the process
• By creating future competition (and inevitable bottlenecks) in the capacity and capabilities of the overall global cold chain, as all stakeholders in the cold chain prepare to meet the swift, global demand that will arrive soon, to deliver unprecedented volumes of COVID-19 vaccines (likely at cryogenic temperatures), once they are approved

Upstream challenges

The upstream process to both harvest blood and stem cells from patients, send those biological materials to dedicated biopharma facilities to create the custom CGT, and deliver them back to the clinical setting where the therapy will be infused into the patient relies on reliable, predictable, tightly integrated operations being carried out in hospitals, apheresis centers and other clinical settings. COVID-19 has created considerable risk and disruption to all clinical settings, undermining their ability to carry out normal activities as planned.

Whether the donor is the same patient who will ultimately receive the resulting CGT therapy at the same clinic (the autologous or “vein-to-vein” pathway), or is an approved third-party donor whose blood or tissue will be used to produce CGT therapies that will ultimately be administered to multiple patients in disparate locations (the allogeneic pathway), a variety of factors are upending regular operations in such clinical settings. These include:

• Increased concern on behalf of patients, in terms of whether travel to the clinical setting and time spent there may increase their risk of infection
• Reallocation of clinical space or practitioners’ attention to focus on COVID-19 patients
• Changing norms and requirements related to reduced scheduling and increased social distancing, travel restrictions and more

(Even further upstream, the clinical trials already underway to advance promising investigational CGTs are also being slowed down as trials have been suspended or postponed and trial enrollment has been challenged due to COVID-19. These disruptions will further delay potential commercial availability of these lifesaving therapies, but that is beyond the scope of this .)

Downstream challenges

The downstream processes in CGT (once the blood or tissue samples have been collected) require that painstaking efforts be undertaken to safeguard the temperature- and time-sensitive materials throughout their multi-step journey, as they move to the biopharmaceutical company’s centralized manufacturing site and ultimately back to the clinical setting for infusion into the patients. This highly coordinated cold-chain storage and transport process typically requires the time- and-temperature sensitive cargo to remain in transit for several days.

With countless flight delays and cancellations, and other pandemic-related disruptions, COVID-19 interruptions increase the risk of temperature excursions that would jeopardize the integrity of both the starting biological materials and the bioengineered therapies, creating extreme clinical and financial implications as these therapies are both vital and extremely extensive. As such, there is very little room for error here.

Moving from “white glove” to “smart shippers” can reinforce the CGT supply chain

Efforts to safeguard CGT shipments by relying on a “white glove” approach to chain-of-custody management have been a hallmark of the early years of the CGT industry. Such herculean efforts often rely on the use of dedicated human “couriers on board” who work to ensure the timely movement and door-to-door delivery of these high-value packages. Such efforts have, on occasion, required chartering.

Instead, stakeholders throughout the CGT arena should increase their reliance on technology-based solutions, which can help them to address delays that can arise as a result of COVID-19 and other challenges. Smart technology-based options include the use of sophisticated, long-duration packaging and shipping options that are able to maintain refrigerated and deep frozen temperatures using state-of-the-art insulation and other design advances.

Long-duration shippers also benefit from payload-condition sensors and integrated telemetry devices inside the packaging. Such smart devices provide tracking and notifications that allow stakeholders to monitor the condition of the shipment in real-time and intervene more quickly, if needed. The ability to keep a close eye on the location and condition of the package supports the strict overall chain-of-custody requirements that are so critical within the CGT arena.

Advanced shippers with state-of-the-art monitoring devices help CGT packages to avoid potential damage from travel and delivery delays by maintaining the biologic materials at the required refrigerated or deep frozen temperatures and helps to reduce the dependence on historic “white glove/courier-on-board” approach. Systems designed with these devices can provide real-time alerts for extended idle time, geofencing of routes, open alerts, shock and vibration alerts and more. Such advanced shipping containers and the data-driven insights they offer can help to maintain both precious CGT raw materials and high-value CGT finished products at the desired temperature for longer periods of time, allowing them to remain safe even in the face of travel and delivery delays.

Similarly, to safeguard the CGT cold chain in the face of COVID-19 (and other) delays, CGT producers should focus more heavily on contingency planning and strategic partnerships that enable rapid workaround solutions and fortify the supply chain allowing high-value cargo to weather the delays that can threaten to break links in the chain and still arrive intact and on time.

For example, when CGT stakeholders partner with larger carriers — such as those that have more redundant assets in place — these service providers are often able to quickly reroute shipments or in some cases the actual trucks, ships and planes as needed in the event of travel disruptions. This has the potential to give the cold chain “self-healing” attributes that can greatly reduce risk, safeguard the time- and temperature-sensitive cargo, and allow for more flexible and scalable solutions.

Closing thoughts

COVID-19 may be the first global pandemic to impact the nascent CGT industry, but it is not necessarily the last global event to strain the system. The lessons learned today, and the resulting upgrades in technology advances related to monitoring, data analytics, temperature-controlled packaging and more, along with more comprehensive strategic planning and modeling of “what if” scenarios and workaround solutions will create stronger, more resilient supply chains for these high-cost, lifesaving therapies. Implementing the upgrades. The need for improved real-time visibility and the importance of planning and partnerships that allow stakeholders to intervene quickly and effectively cannot be overstated. COVID-19 has underscored the need for all CGT stakeholders to invest in a paradigm shift that can both improve cold chain reliability and reduce risk.

Despite the impact of COVID-19, the maxim “It’s not a package, it’s a patient,” remains an absolute guiding principle throughout the CGT arena. At the end of the day, there is an actual immunocompromised patient waiting anxiously for the therapy to arrive safely, without incident, and with no temperature excursions that could compromise the integrity of the lifesaving therapy. Getting it right the first time is the only option, despite the added layer of unpredictability imposed by COVID-19.