While the cell and gene therapies approved so far are indicated for rare diseases with small patient populations, the successes of chimeric antigen receptor-T (CAR-T) therapies and expanding interest from biopharma stress the need to rapidly scale the supply chain as these therapies move toward commercial availability for more disease states and larger patient populations.
Hailing the approval of tisagenlecleucel (Kymriah) in 2017, the first gene therapy to receive approval in the United States, then-FDA Commissioner Scott Gottlieb, MD, said, “We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer. New technologies such as gene and cell therapies hold out the potential to transform medicine…”
With cell and gene therapies emerging as innovative treatment options for many cancers and other rare diseases, there are currently thousands of cell and gene therapies in the development and commercialization pipeline. As a result, the FDA is preparing for a wave of experimental therapies, and by 2025, the FDA may approve 10 to 20 new cell and gene therapy products a year.
Based on the potential of this next generation of drug therapies, top biopharma companies have built cell and gene therapy into their strategic growth plans, as evidenced by recent acquisitions and collaborative partnerships. For example, Novartis has led the way in securing approvals for Kymriah and onasemnogene abeparvovec-xioi (Zolgensma), the first gene therapy for children under 2 for spinal muscular atrophy, and the acquisition of AveXis. Other activity has included Gilead’s acquisition of Kite Pharma, Roche’s acquisition of Spark Therapeutics, and Bristol-Myers Squibb’s acquisition of Celgene.
Scaling the Supply Chain for Growth and Broader Impact
While the therapies approved so far are indicated for rare diseases with small patient populations, the successes of chimeric antigen receptor-T (CAR-T) therapies and expanding interest from biopharma stress the need to rapidly scale the supply chain as these therapies move toward commercial availability for more disease states and larger patient populations.
Whether the products are autologous or allogeneic in nature, understanding complex logistical requirements for transportation, storage, and data tracking is critical to maintain access and patient safety. In this article, we will review key limitations to the supply chain that must be addressed to support the growth and distribution of cell and gene therapies for broader impact, including scaling cold chain management, maintaining chain of identity and enabling just in time shipping for the last mile.
Cold Chain Management
As the industry continues to move from small molecule drugs to biologics and cell-based therapies, the need for temperature-controlled storage and transportation increases. Cold chain management has always been a key component of the cell and gene therapy supply chain, but now it’s a matter of scale.
For example, as more therapies come to market and the supply chain expands on a global level, this means new and multiple manufacturing locations, new regions that products are being shipped to and from, and most importantly, new clinical sites and settings. This translates to new pick up points, new drop points, more exchanges and handoffs, all of which add challenges to maintaining a stable, constant temperature throughout the supply chain. What was once a process of monitoring the temperature and status of a single shipping container now requires constant monitoring of each individual package.
To mitigate this risk, biopharma companies can work with third-party logistics (3PL) suppliers to help with everything from order fulfillment and payment to product distribution and delivery, as well as flexible temperature-controlled packaging solutions.
Chain of Identity
It is not enough for biopharma companies to simply optimize supply chain logistics; they must implement patient-centric strategies to ensure patient access and safety. This requires a new mindset that places the patient at the epicenter of everything from clinical development to supply chain management and ongoing engagement and adherence. It’s critical that every person who handles these therapies understands his/her unique requirements and remains vigilant in safeguarding each shipment. This will move cell and gene therapy from an emerging new therapeutic approach to a critical tool for delivering life-saving medications to the right patients at the right time. This as an opportunity to start establishing standards to protect and scale as these therapies come to market, including processing of receipt of the therapy and confirming data—what data should be there, what data to verify, what happens if it is the wrong identifier number, what happens if the package is damaged?
Because autologous cell therapies are personalized products created for each specific patient, biopharma companies must ensure that the chain of identity is maintained and verified throughout the entire supply chain, no matter how complex. Unlike conventional, large batch drugs, each cell and gene therapy patient represents his/her own batch, and with treatments such as CAR T-cell therapy, the patient is literally the first step of the supply chain. Few manufacturers have the systems in place to track the condition of the cells from the moment that the blood draw happens to the time that the therapy is reinfused, so McKesson leverages industry collaborators for robust data tracking and verification capabilities to help preserve chain of custody and identity. However, this is more involved than simply tracking the delivery of a package from an online shopping site. This is about building the infrastructure to track and verify that life-saving medications get to patients safely and efficiently in order to drive the best possible outcomes.
Just-in-Time Shipping for the Last Mile
Some cell and gene therapies have shorter shelf lives than traditional medicines which, when combined with their high cost, makes it impractical to ship these drugs through normal channels. Temperature-controlled drugs are especially vulnerable in what is often referred to as the “last mile” when products can be delayed at the final step along the supply chain—getting from the local distribution center to the patient or to the care facility for administration.
As a result, biopharma companies have to rethink their distribution channels to avoid treatment delays. More products are now managed using a just-in-time approach that utilizes overnight delivery to fulfill next-day service to patients and providers. In addition to developing relationships with parcel companies that can accommodate complex logistics, this requires patient-centric communication and coordination with the care center 24-48 hours before anticipated delivery so they can schedule the patient for an infusion accordingly. All of the efforts to maintain chain of custody and temperature controls are for naught if the package sits on a loading dock beyond its expiration date.
Leveraging Expertise in Specialty Pharmaceuticals
While the cell and gene therapy market is poised for tremendous growth and impact on patient care, the supply chain needed to support this growth is not yet fully formed and scalable. This is very analogous to where the specialty drug market was 20 years ago, which propelled investment in cold chain management and integrated support to drive access and commercial success. As an industry of biopharma manufacturers, suppliers and distributors, we have an opportunity to leverage our expertise with specialty drugs to fuel the transition from small-batches to larger volumes by addressing key limitations through technology, software solutions and customized support services.
Ultimately, this is about the patients and ensuing they have the best possible experience and outcomes. If the patient never knows how much effort it took to deliver their CAR-T therapy, the supply chain is working.