Over the past year, the COVID-19 pandemic significantly disrupted clinical research across the lifecycle including recruitment challenges, protocol amendments and delayed market entry.
At the root of many of these setbacks is disrupted manufacturing and supply chain processes. This holds particularly true for cell therapies, which already required additional considerations when it comes to processing, packaging and shipping compared to traditional biologic drugs.
Because cell therapies are fundamentally “living therapies,” orchestrating the logistics for both source materials and final doses of these therapies requires detailed planning and hands-on management. The end-to-end processes of tracking and tracing the movement and handoffs of these shipments among stakeholders are rife with risk and potential points of failure. With this in mind, cell therapy developers have had to adopt flexible strategies to adapt to the evolving COVID-19 landscape. Here we discuss the unique challenges of manufacturing cell therapies, and how restrictions caused by the pandemic have placed additional pressures on developers.
Exploring the unique challenges of cell therapy development
Part of what makes the development of cell therapies so unique is that they require the use of living cells, either from a donor (allogenic) or from a patient’s own cells (autologous). Using autologous cell therapies often means the manufacturing process must accommodate for the variability in the source patient’s cells to consistently produce a final product that has the desired attributes. With this in mind, it is critical that cell therapy developers maintain the chain-of-identity for each product starting with initial collection to transportation throughout the manufacturing process until the final product is administered. Each handoff must be closely monitored and samples require detailed tracking and tracing.
Moreover, these therapies require highly coordinated schedules for each stakeholder and delivery timelines. For example, because manufacturing capacity can be a critical factor for autologous therapies, schedules need to be coordinated between labs, apheresis centers, specialty couriers and the manufacturing centre to collect the cells and ship them overnight to the manufacturing facility. These refrigerated shipments are time sensitive, requiring the manufacturer to be ready to start the process upon receipt. As such, disruption at any point of this process can pose risks for both the product and the patient.
In addition to shipment scheduling, these trials require a high level of coordination for patients. Cell therapy trials often require patients to travel to specialty centers to receive treatment. As such, close coordination between sites, patients and their caregivers is necessary. Any change in the schedule can affect the entire workflow of the trial, and can result in errors with regards to maintaining the chain of custody of the product.
Additional considerations during COVID-19
Due to the increased demands of cell therapy trials and the delicate nature of these products, restrictions imposed by the COVID-19 pandemic have created a significant threat to these trials compared to traditional biologic products. For example, the closure of borders and reduced air traffic can affect the supply chain to and from clinical research sites, resulting in delayed transport of resources. Shortages of supplies have, in some cases, caused service providers to shut down entirely. Because transport logistics are so critical for cell therapies, closure of clinical research sites can put the viability of entire trials at risk. Moreover, with many of these therapies requiring hands-on management and temperature monitoring, flight delays due to COVID-19 have been a primary concern for cell therapy developers.
To compound the issue of clinical sites being shut down and supply chains being delayed, some apheresis centers chose to reduce schedules or stop operating entirely in an effort to limit the exposure of site staff to COVID-19. For sites concerned about exposing vulnerable patients to the virus, appointments may have been delayed or cancelled. This prevented participants from having access to therapies and negatively affected enrolment and retention of patients. To mitigate this challenge moving forward, restricted access to healthcare facilities as well as new COVID-19 safety and screening procedures should be included in protocols.
Conclusion
The restrictions imposed by COVID-19 have resulted in disruptions to clinical research including changes to site procedures, patient re-scheduling and shipment delays. Until COVID-19 vaccines have been widely administered, these challenges are anticipated to persist. Continuing to find ways to ensure supply chain resilience and keep development programmes on track requires ongoing innovation and flexibility. To learn more about how ICON can help keep your trial on track during COVID-19, please visit: https://www.iconplc.com/solutions/clinical-and-scientific-operations/covid-19/.