Personalized Medicine, Personalized Supply Chain?
How will digitalization help manufacturing of Car-T cell therapies scale when patients are part of the supply chain?
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. [1] 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] [2].
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). [3]
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. [4]
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. [5]
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 [6]. 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. [6]
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. [7]
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. [5]
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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[1] Novartis.com. (2017). Novartis receives first ever FDA approval... [online] Available at: https://www.novartis.com/news/media-releases/novartis-receives-first-ever-fda-approval-car-t-cell-therapy-kymriahtm-ctl019 [Accessed 15 Nov. 2017].
[2] Bioprocessintl.com. (2015). The Cell Therapy Supply Chain. [online] Available at: http://www.bioprocessintl.com/manufacturing/cell-therapies/the-cell-therapy-supply-chain-logistical-considerations-for-autologous-immunotherapies/ [Accessed 15 Nov. 2017].
[3] BioPharma-Reporter.com (2017). Dude where’s my Car-T? [online] Available at: https://www.biopharma-reporter.com/Article/2017/09/01/Novartis-must-prove-it-can-handle-complex-CAR-T-supply-chain-TrakCel [Accessed 15 Nov. 2017].
[4] Nature, Cancer Gene Therapy. (2015). Towards a commercial process for the manufacture of genetically modified T cells for therapy [online] Available at: https://www.nature.com/articles/cgt201478 [Accessed 15 Nov. 2017].
[5] Bio Insights. (2016). Visualizing the cell and gene therapy supply chain of the future. [online] Available at: http://insights.bio/cell-and-gene-therapy-insights/?bio_journals=visualizing-the-cell-and-gene-therapy-supply-chain-of-the-future [Accessed 15 Nov. 2017].
[6] BioWorld. (2017). As Novartis ‘CAR Ts’ Kymriah to market, race for next-gen winners moves into high gear. [online] Available at: http://www.bioworld.com/content/novartis-car-ts-kymriah-market-race-next-gen-winners-moves-high-gear-0 [Accessed 15 Nov. 2017].
[7] BioPharmaDive. (2017). Novartis taps Cryoport for CAR-T logistics support. [online] Available at: https://www.biopharmadive.com/news/novartis-cryoport-car-t-logistics-shipping-cryopreservation/448060/ [Accessed 15 Nov. 2017].
This is an interesting example of digitization in the supply chain. End-to-end control and visibility of the supply chain provides benefits to industries as basic as beer production and distribution, but it makes sense that the high tech medical treatment companies are leading the charge given their price per product, low shelf life, and specific transportation needs. I find it interesting that one central location in the US is responsible for all manufacturing, and that the plant is on the east cost instead of a more central location. Perhaps the plan is to build a west coast location when demand warrants a 2nd facility.
Thanks a lot for this article. I had no idea such treatments were being developed.
I am wondering whether it would make sense to have a more decentralized supply chain, with most of the activities being performed inside hospitals in their current labs. Of course, many things could prevent that: lab capacity, the availability of the right equipment, the willingness of the pharmaceutical industry to send lab workers to the hospitals. It is also unclear to me whether such a model would be scalable, and at what price.
This impressive new technology has led to unprecedented supply chain complications. As the author and other comments have pointed out, it seems that a key challenge may be expanding this model past 35 treatment centers, and additional points of manufacturing may be needed. Perhaps an even bigger challenge will be how to manage such a system as customized cell therapies and other forms of personalized medicine become more commonplace. How will a hospital be able to track and coordinate many different therapies with many different manufacturers? This could require hospitals to build an entirely new digital infrastructure to coordinate logistics in order to ensure that the time-sensitive therapies are delivered to patients on time.
I think the promise of personalized medicine really puts pressure on the traditional healthcare supply chain. As you pointed out, the time-sensitive, personalized and critical nature of this product makes the problem very difficult to solve. It seems like Novartis has taken the approach of integrating and controlling more of its supply chain, which makes scaling hard – particularly as one things about internationalization. Novartis may also want to consider A/B testing a part of its supply chain where it does not adopt an end-to-end model but rather develops a playbook for delivering this treatment. There may be optimal ways to educate current members of the supply chain on the requirements of this new system, software that can make information sharing easier and best practices / policies to implement.
As we enter the period of more personalized medicine such as CAR-T and more genomics sequencing, the problem of production comes more and more into play. The question I have regarding this is: are there enough patient demand for a need to scale? We’ll need to know the future demand and whether it’s a wise idea to scale if there are frequent switches in the technology. Second question I have is whether patient sampling is really the bottleneck. The drug delivery process is inevitable coupled with hospital operations, which involves clinic booking, which often also takes time. Therefore, I think it is important to simplify and enable a more efficient drug production, while it is also prudent and forecast future demand both in patients and changing in technology that may make CAR-T less relevant.
Thanks Author for bringing attention to these leading-edge cancer treatments. It’s no question that immuno-oncology and gene therapy have become a massive area of research and development for big pharma [1], but I wonder if there are other players than Novartis who are better equipped to handle the supply chain and logistics piece of this puzzle? For example, McKesson, who has been doing drug supply chain for decades, acquired two businesses in the oncology space in February 2016, one of which provides rapid and traceable oncology pharmaceutical delivery solutions [2]. In addition, there are several life science cold-chain logistics players such as CSafe and Envirotainer that also have some expertise in time and temperature sensitive shipments. It seems critical to either decentralize production, as others have pointed out, or leverage existing industry players who have the manufacturing and distribution lines already established in order to expand beyond the 35 treatment centers. Novartis appears to have taken such a hard stance on developing the capabilities internally that it is unlikely they try that route, but nonetheless I think it will be a particularly difficult road ahead to accomplish their vision. Finally, while Cell-T and other treatments like it are exciting to consider, it is still very early days in the approval and efficacy process for many of these treatments and a wholesale investment in a sophisticated and robust supply chain may be premature.
[1] QuintilesIMS, “Global Oncology Trends 2017, Advances, Complexity and Cost”, June 2017. , Accessed November 2017.
[2] McKesson Expands Oncology Expertise with the Acquisitions of Vantage Oncology and Biologics
February 25, 2016
[3] Rodríguez Fernández, Clara, “A Cure for Cancer? How CAR-T Therapy is Revolutionizing Oncology” Labiotech.eu, posted on July 3, 2017. , Accessed November 2017.
The supply chain challenges that plague CAR T cell therapies are an example of how manufacturing and logistical constraints can fundamentally impact the focus of research and development. In this case, a high-functioning supply chain is not simply a question of system optimization; it’s a gating issue for sustainable commercialization. If Novartis is unable to maintain an efficient supply chain at a large scale, as the author suggests, this has the potential to shift research at the company toward more easily deliverable alternatives.
Despite the challenges that Novartis faces in developing the infrastructure to support novel therapies, the pharmaceutical industry is broadly seeing rapid digitalization and increases in supply chain efficiency that will benefit the company. Heightened expectations of responsiveness from patients, medical specialists, and suppliers alike have increased interconnectedness and transparency across the supply chain. This provides the groundwork for the high-functioning system that Novartis demands [1].
1. Champagne D, Hung A, Leclerc O. The Road to Digital Success in Pharma.; 2015. https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/the-road-to-digital-success-in-pharma.