How do you efficiently and safely mass produce a time-sensitive therapy for which the patient is part of the supply chain? This is the fundamental question that Novartis and others developing cell therapies are wrestling with as these novel treatments begin their uncharted path to commercialization.
Novartis’ Kymriah, the first gene-modified cell therapy approved in the US, is a CAR-T autologous therapy trained to attack cancer cells.  The supply chain complication? This therapy requires T cells be extracted from a patient’s blood, re-engineered or ‘trained’ in a lab to recognize and kill cancer cells, and then re-infused back into the patient, a process that may require 5 different shipments of 3 different materials at 4 different temperatures [Fig. 1] .
Digitalization crucial for managing manufacturing capacity
Given the convoluted manufacturing and shipping process, strict quality and safety requirements, and T-cells’ short shelf-life, the structure and logistics of the supply chain will be particularly complex. Of key importance will be capacity management. Hospitals and providers will need to be given advanced notice of when a patient’s cell needs to be collected and this must be conducted at a time when capacity is available for all other stakeholders responsible for downstream activities (e.g., manufacturers must be alerted when material is on its way to set aside necessary capacity). 
Unlike typical drugs that can be mass produced based on estimated demand, cell therapy production will be heavily dependent on patients’ highly variable schedules. Additionally, as more cell therapy treatments are approved and marketed, the supply chain will become significantly more complicated and competitive. The numbers of patients, samples and treatment centers will rise, and the steps along the chain may be magnified as hand-offs increase from nurses to couriers, expanding the risk for mistakes or losses. 
Today’s pharmaceutical supply chain is too siloed across different stakeholders to effectively manage this complexity, resulting in an open-ended system that provides massive room for error. Technology in the pharmaceutical supply chain will need to evolve and digitalization will be key. Processes must transition towards a fully connected and closed system in which every aspect of the drug, from sample collection to manufacturing to infusion are tracked from end to end. 
Deep pockets allow for an end-to-end solution
Novartis, with its existing in-house manufacturing capabilities and access to significant capital, has taken steps to build a system that anticipates potential supply chain challenges.
Reimagining the supply chain into healthcare service
Novartis believes its ability to build a sustainable manufacturing process and supply chain is one of its key differentiators against competitors . It has focused on providing an end-to-end solution that is more akin to a healthcare service than traditional drug delivery. At its 180,000 sq-ft facility in Morris Plains, NJ, Novartis has designed “a robust, reproducible and scalable manufacturing and supply chain platform to provide this individualized treatment approach on a global scale”, encompassing facilities, equipment, personnel, and logistics rolled into one. A digital solution will employ end-to-end tracking as well as integrated planning and execution systems, logistics visibility, and advanced analytics to properly monitor the manufacturing pathway and anticipate fluctuations or variability in demand. 
Cryogenic support and premium couriers
Novartis has also contracted with 35 treatment centers for distribution of Kymriah in the US and signed a 3-year deal with Cryoport, a cold chain logistics solutions provider, for cryogenic support. “This partnership personalizes the process for Kymriah and will help facilitate a more efficient and straightforward process between Kymriah’s manufacturing facility in Morris Plains, New Jersey to its 35 treatment sites in the US.” With this deal, Novartis will be able to access Cryoport’s shipping containers, digital condition monitoring system, and advanced logistics management platform. Additionally, cryopreservation can prolong the shelf life of cellular material and provide physicians and patients with flexibility when considering treatment sequencing. 
Considerations for the future
Novartis should also consider ways to connect and manage data flow. Potential solutions include the ability to monitor shipments with real time, GPS-enabled data as well as consolidation of multiple variabilities in the system such as temperature, location, equipment qualification, and validation in order to have a robust quality management system. Partnerships with major digital players will also be important in the mid-term, and special consideration should be given to companies such as GE Healthcare’s Cell Therapy Technologies, which has built digital platforms (e.g., Vitruvian network) and developed software and tools to solve data problems specifically related to digital supply chain management of complex therapies. 
Key questions – Can Novartis increase the number of treatment centers significantly beyond 35, or will maintaining sustainability and efficiency on a large scale be impossible with this type of therapy? How will the supply chain be impacted as this drug expands internationally and faces geographical shipping challenges and regulations?
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