By Joy Aho, PhD, Senior Product Manager, Be The Match BioTherapies
We’re living through unprecedented times, both as individuals and as a nascent cell therapy field. The pandemic has had negative implications for manufacturing and shipping across nearly all industries, including very pronounced negative implications on the specialized, time-sensitive supply chain that supports cell therapies. Meanwhile, the pandemic’s effects on health care have shifted priorities at the point of care, impacting basic services for clinical study launch and existing study continuity.
We at Be The Match BioTherapies® have been coordinating closely with hospitals, apheresis centers, cell and gene therapy developers, and logistics vendors among others to navigate this uncertain environment. And though it’s a distressing time, our teams and our industry are rising to the challenge, knowing that the therapies we support have never been more critical and we cannot lose sight of the patients who need access to these therapies to survive.
Assessing the Impacts on Cell Therapy
The impact of the COVID-19 pandemic on the cell therapy industry was immediate and drastic. The cell therapy supply chain, already logistically complicated, has faced new challenges each day that have only increased as the disease has spread.
According to the latest stats from FlightAware, an average of 30–50% of flights into, within, or outside of the U.S. are canceled daily, amounting to more than 10,000 delays or cancellations each day. A significant proportion of cell therapy transports are conducted by commercial flights, so these cancellations have had far-reaching effects on the movement of time-critical cell therapies. Additionally, many couriers are being prevented from traveling internationally due to border restrictions in various EU countries, which can change very rapidly, as we saw with President Trump’s Europe travel ban in mid-March. Couriers whose underlying conditions and age put them at a greater risk for COVID-19 infection have been further deterred from travel. More effort and expertise are required to minimize risk within the supply chain.
Additionally, biopharmaceutical companies, including major players like Pfizer and Eli Lilly, are announcing clinical trial delays. The impact on allogeneic cell therapies, or cell therapies derived from a healthy donor, has been particularly acute. Due to social distancing restrictions, allogeneic donors are less likely — and often unable — to donate their cells. This has caused delays in cell collection that ripple throughout the entire allogeneic cell therapy supply chain.
Autologous cell therapy, which utilizes cells collected directly from a patient, is being impacted in different, but still challenging ways. The cell collection process involves multiple steps that require human-to-human interactions, including a visit to an apheresis center and interaction with one or more apheresis technicians. Additionally, there are often pre-therapy treatment regimens that can put patients at risk by compromising their immune systems. Further, autologous cell therapies quite often rely on the shipment of non-cryopreserved cells to and from a centralized manufacturing facility within very tight timeframes. Disruptions to travel itineraries puts those shipments at risk. Patients and clinicians are having to make difficult decisions about the safety and timing of administering autologous cell therapies in a high-risk environment, and increasingly are opting to delay the administration of these therapies whenever possible.
As continued evaluation of COVID-19 cases underscores that people with underlying conditions are disproportionately affected by the virus, many patients whose therapeutic need is not immediate are choosing to wait rather than risk exposure. Some of them do not have a choice, as over time more apheresis centers are advocating to close their doors, both to minimize risk of infecting workers and patients and to deploy more healthcare personnel to help fight the virus.
In short, treating and abating COVID-19 has become everyone’s top priority. However, critical health care needs like treatments for cancer and rare genetic diseases still remain essential — and it’s our responsibility in the cell therapy industry to formulate the processes to deliver them.
Adjusting to Keep Therapies Accessible
We and others in the cell therapy industry have rapidly implemented contingency plans to ensure that essential medical treatments are still being produced and delivered. Because the pandemic has had ramifications on many different elements of the cell therapy ecosystem, we have been actively problem-solving on many different fronts in collaboration with our wide network of apheresis centers, clinical sites, logistics vendors and biopharmaceutical partners.
One of the bigger shifts we’ve made is in donor collection processes. We are working to put processes in place to minimize risk to potential donors. This includes minimizing donor travel by evaluating donor selection based on location and aligning that with current apheresis capabilities. Every allogeneic donor is being evaluated on a therapy-specific and donor-specific basis to ensure donor safety.
As some of the apheresis centers in our network, especially in hard-hit areas, have temporarily suspended operations, we are coordinating with other nearby facilities to redirect donors. We’re maintaining daily contact with our network of 84 apheresis centers to understand the clinical and regulatory challenges that are being faced regionally. It’s a testament to the strength of our network, our collaborative partners, and the consistency of adherence to our protocols that we are able to quickly reassign collection from one facility to another and still be assured that the end product will be of equally high quality.
Of course, this flexibility in collection location also means we have to be agile in the management of shipping logistics. Factor in the widespread flight cancellations and travel restrictions in the EU and in some U.S. cities, and there are a lot of challenges to plan for in parallel. We and our parent company NMDP/Be The Match have worked with the CDC to get a waiver on travel restrictions for those foreign nationals who are transporting life-saving cell therapy products to the U.S., and we’re working with overseas authorities to implement the same protections in their countries. To contend with the flight cancellations, our Logistics Management specialists and dedicated team of travel agents can reschedule travel in real-time to adjust to changing circumstances. And at the highest level, our strong relationships with marrow donor registries around the world mean that we have local allies who can help advocate for policies that ensure the free movement of cell therapy couriers.
Looking to the Future
At some point, this pandemic will end. Though these next few weeks and months will be difficult, we hope to learn from this experience and apply those learnings to our work of getting life-saving therapies to patients.
One of those learnings might have to do with broader use of cryopreservation. In future periods of disruption to collection centers, cryopreservation may be a way to ensure continued patient access to therapies by banking cellular material over time. And utilizing this process more broadly, even outside of emergency situations, may allow cell collection nearer to patients, minimizing the complications that transit presents even in the best of times. As an industry, we will have to learn more about the clinical implications of freezing cells for allogeneic cell therapies. There may be particular impacts on therapeutic efficacy for some products undergoing cryopreservation, and we should work to gain a better understanding of those consequences.
Another means of optimizing the cell therapy supply chain, and making it more resilient to disruption, is to have a broad base of donors. Early-stage allogeneic companies today are often relying on a small number of so-called “super donors” from which to source their cell therapies, but this approach is far from fail-safe. We believe that as the industry grows it will need to exponentially widen its donor pool; doing so will serve as an additional insurance policy against future disruptions.
Once we are through this period, we expect that the industry as a whole will continue to retrospectively assess where other strains on the cell therapy supply chain materialized and what lessons we can learn from our response.
But in the meantime, we plan to keep problem-solving, keep rolling with the punches, and without fail, keep delivering these therapies to the patients who need them most.