Cell & gene therapy (CGT) companies have faced unique challenges due to the nature of their therapies. This has been especially true for autologous cell therapies, where the pandemic’s impact has challenged the intricate and complex supply chains coordinating patients, practitioners, and manufacturers. These autologous therapies, such as Adaptimmune’s SPEAR T-cells, generally start with the collection of leukocytes (white blood cells) from patients being treated for various types of cancers. The cells, collected by a process called apheresis, are shipped to a centralized manufacturing site. In the case of Adaptimmune’s therapies, the T-cells are then isolated, genetically-modified, and expanded in cell culture to produce engineered SPEAR T-cells. These engineered SPEAR T-cells, with enhanced functionality to recognize and attack the patient’s specific type of cancer, are then infused back into the patients.
This “one patient - one batch” manufacturing strategy requires a broad range of specialized raw materials and consumables, flexible manufacturing capacity, and a highly skilled workforce for cell processing, testing, batch release, and product logistics.
Unique Considerations for Autologous Cell Therapy Companies
While CGT companies have remained committed to manufacturing and delivering these critical life-sustaining therapies during the pandemic, several challenges require proactive and intensive mitigation. Foremost is the greater volatility in patient’s ability to travel in conjunction with access to clinical sites, both for the initial apheresis and for the subsequent infusion of the engineered cells, due to very real concerns regarding potential exposure to COVID-19 while in travel or at the treatment center. Patient scheduling can also be disrupted by the availability of healthcare professionals who may have been re-deployed to support their colleagues on the front line of the pandemic. Even when patients and their healthcare providers can keep their appointments, disruptions to commercial airline schedules can put the timely transport of cell materials between the clinic and the manufacturing site (and vice versa) at risk.
The volatility in patient scheduling leads directly to higher variability in manufacturing scheduling, which may already be challenged by the fluctuating availability of the workforce or by shortages in critical raw materials, components or even PPE supplies.
Mitigating the Uncertainties
It is essential for autologous CGT companies to find solutions to these and other issues, while at the same time protecting the safety and health of their own employees. At Adaptimmune, we have taken several steps to ensure the uninterrupted supply of our SPEAR T-cells under these challenging conditions as well as mitigate risk – both of which are in a process of continuous improvement. Though these steps have been effective to mitigate the risks and uncertainties known to us in the current global supply climate, we continue to take proactive steps to ensure we can continue to deliver life-sustaining therapies to people with cancer.
For example, we are exploring alternate apheresis centers (separate from the treatment sites) that may be closer to the patient and not as heavily impacted as the large hospitals where treatment steps for our therapies are typically performed. This may make the patient journey easier in a way that also mitigates potential exposure to COVID-19 at large treatment centers. We are also decoupling the initial collection of T-cells from the subsequent re-infusion of engineered T-cells by manufacturing and storing cells to be infused later, when the clinical site is better able to accommodate the patient and procedure.
To address potential disruptions to air transportation routes, we are utilizing ground transportation in the Eastern United States, whenever possible. When this is not feasible, or the distances are too great to ship the materials safely by ground, we have established contingency plans with our logistics partner to transport cells via chartered flights if commercial flights are unavailable.
To mitigate potential shortages in raw materials and components, we began increasing our inventories as early as February 2020 for critical materials. This action, in conjunction with our secondary source planning, has enabled us to significantly increase our safety stock levels to carry us through intermittent disruptions.
Finally, to keep our employees safe we implemented a work-from-home policy for all employees not directly necessary for product supply; thereby reducing the risk of COVID-19 transmission for those employees required to be on-site. For those employees on-site, we adapted our procedures to be consistent with the CDC/OSHA/WHO guidelines, including enforced social distancing, increased frequency and extent of cleaning for all areas, requiring the use of masks at all times, implementing temperature checks upon entering the facilities, and rapid tracking/tracing of any employees with potential symptoms to enable broader, temporary self-quarantines to stem any potential viral transmission.
Being Prepared for Anything
Like many other companies, we are adapting our supply chain planning processes to ensure we have everything needed for manufacturing, and we are increasing communications with respect to operations to keep our facilities and transportation running safely and effectively.
The COVID-19 pandemic has challenged all supply chain professionals to do what is required to maintain critical operations during unprecedented, global disruptions. At Adaptimmune and across the CGT industry, CGT professionals are finding ways to provide critical therapies to people with cancer. Ultimately, we will emerge with stronger supply chains and the confidence that these complex manufacturing processes can continue to operate in the most trying of circumstances.
Mark Stielow is the Senior Director of Cell Manufacturing & Technical Operations at Adaptimmune. Mark holds a Bachelor’s degree in Chemical Engineering from the University of Wisconsin, and a Masters of Management degree from the Northwestern Kellogg Graduate School.