May 24, 2019 PAP-Q2-2019-CL-025
With hundreds of potential products advancing through early into late-stage clinical trials and scaling up to commercialization, the market for cell and gene therapies is expected to grow dramatically in the coming years. While only three cell and gene therapies have achieved FDA approval to date, former FDA Commissioner Scott Gottlieb predicted an approval rate of 10–20 cell and gene therapy products per year by 2025.1 The value of the global market for cell and gene therapies is predicted to expand at a compound annual growth rate of nearly 22%, growing from $6.02 billion in 2017 to $35.4 billion in 2026.2
With autologous therapies, biological material is collected directly from the patient via apheresis. The material is transferred to the manufacturing site, where the cells are genetically modified and produced in large quantities. The personalized therapy is then shipped back to the clinic and administered to the patient. Both the initial material and therapy must be shipped under liquid nitrogen (LN2) or refrigerated conditions in a very short period of time — for the cell collection, the typical door-to-door transport time is 40–50 hours or less. The therapy transfer requires strict temperature and chain of identity monitoring.
The same is true for allogeneic therapies, once the cells have been modified, grown and processed into the final medicinal product. The ability to deliver material to the manufacturing site and/or back to the clinic depends on the location of the two sites and the availability of modes of transport.
Autologous cell therapies create scheduling challenges as well. In many cases, these products are produced at a contract manufacturing organization (CMO). Coordination between the material collection, transport and receiving hours at the CMO is a vital element managed manually in early stages and often supported by IT solutions when scaling up to phase III or commercial stage.
Allogeneic therapies are produced from cells that are collected from a healthy donor, stored under liquid nitrogen at a low temperature and shipped to a clinical site to treat a patient with a successful match. A just-in-time delivery process, including secondary packaging, labeling and QP release (in the EU) is necessary.
Errors along any point of the process or supply chain can be potentially devastating for patients and highly costly for clinical trial sponsors. Analysts estimate that manufacturing of approved CAR-T treatments can cost $200,000–800,000 per dose. Innovative therapies that may not only treat but potentially cure cancer and genetic diseases are promising, but if those therapies cannot be distributed to patients (or the patients cannot be brought to the therapies) they have no value.
The development of smart packaging is a critical element of the supply chain solution. Monitoring and tracking systems embedded in the shipping solution allow real-time access to shipment data such as location, temperature, shock and orientation. If activated, predefined alarm points trigger automated messages, allowing interception of the shipment and the initiation of actions required to keep everything under control. Using GPS, data locations, such as airports or clinics, can be geo-fenced. When shipments enter or leave geo-fenced areas, automated notifications can be sent, assuring that defined individuals are aware of arriving shipments and notified of any excursions.
The challenges and needs for cell and gene therapy supply chains are creating demand for more advanced IT solutions. For many of these drug products, and particularly for autologous cell therapies, logistics are a crucial element in ensuring that the right medication reaches the right patient within a highly specific time frame.
Many factors must be considered in the cell and gene therapy supply chain, such as when the patient should come to the clinic, how long the apheresis collection will take, when the material can be picked up from the clinic, the opening hours for the manufacturing site, the duration of the production process, when the drug product can be picked up and the locations of the two sites, among others. This information is used to identify the best mode of transport and to achieve lane mapping and lane verification.
One of the biggest challenges in autologous therapies is the fact that each batch is produced for one patient. Scaling up does not involve producing more volume in terms of quantity, but rather in terms of the number of batches. Scheduling is also dramatically different when moving from early to late stage and commercialization. At early development stages, scheduling is typically handled with manpower; planners coordinate requests coming in from clinics with available manufacturing capacities and manage the logistics interfaces that connect the various elements of the supply chain. When scaling up, adding more resources does not offer much benefit. The complexity is too great; effective IT systems are essential. When properly linked to the logistics systems, available data can be utilized to automate and forecast upcoming requests.
There are instances where a lane-mapping exercise will lead to the conclusion that no route is available by which the successful delivery of material and/or drug product can be guaranteed within the acceptable time frame. In some cases, the problem can be overcome by collecting the patient sample at an earlier time, or requiring the CMO to offer more flexibility in accepting/dispatching material in order to make it possible to meet existing flight options.
As more cell and gene therapies reach the market, patients may need to be brought closer to the manufacturing site, or a decentralized supply chain approach may need to be implemented. As manufacturing technologies continue to evolve and allow easier control and implementation of modular facilities, the latter option will become more feasible.
As the field of cell and gene therapy expands to address aging and other general conditions, there will be even greater demand for decentralization to enable the delivery of these remedies to the wider population.
The fate of millions of patients and billions of dollars thus rests on the biopharma industry’s ability to master the complex supply chains that underpin the development of advanced therapies. The promising nature of advanced therapeutics and the challenges they pose makes it necessary to choose a supply chain provider that has track record of managing these logistically complex clinical trials.
One of Marken’s core services is collecting and delivering biological samples. We are now leveraging that experience and sophisticated technologies for the collection of apheresis materials and the delivery of novel cell and gene therapy products. Clinics can use our Allegro portal for data entry and shipment requests. Marken’s new Smart Box, a custom-designed thermal box, provides the best protection available for high-value shipments of clinical drug products, clinical drug substance and cell and gene therapies, combined with 24/7 tracking visibility using any one of three different GPS tracking devices. It is the first truly configurable container capable of utilizing any GPS tracking device available, including Marken’s own SENTRY device, which reports location, temperature, movement and shock as often as once per hour. The box can also accommodate Bluetooth technology for temperature monitoring and identification.
Marken also recently introduced an automated closed-loop packaging solution that allows materials to travel at any temperature to any destination with an integrated and automated packaging returns process. The new service allows critical drug shipments traveling in reusable and valuable packaging to return to their point of origin for reconditioning and repositioning with much greater efficiency.
As the clinical supply chain subsidiary of UPS, Marken’s access to UPS’s expansive airline and fleet networks increases Marken’s ability to source appropriate shipping lanes. Shipments are collected by Marken, placed on UPS flights and then carried to their final destination by Marken. The hybrid solution, which covers Europe and the Americas, gives Marken end-to-end oversight and offers more flexibility and resources. In Brazil, the introduction of the service extended the latest pickup times by up to five hours, giving more time to prepare and package samples.
Marken is actively working to develop advanced solutions that facilitate scheduling within the cell and gene therapy supply chain. We are collaborating with a leading supply chain software company, which has developed integrated software technology that effectively and easily orchestrates the cell therapy supply chain for autologous and allogeneic therapies. The interface between the operating systems allows users to automatically schedule or amend material collections in line with manufacturing capacity, and each healthcare provider’s treatment schedules. Clinicians are then able to view the progress of therapies through each stage of the supply chain with a single, integrated system.
Marken utilizes historical data to forecast shipment times and requirements, optimizing the demand planning and scheduling process.
The implementation of smart technologies, along with our extensive network, has given Marken the opportunity to address cell and gene therapy supply chain issues before they occur. Marken is focused on not only providing supply chain logistics for the transport of these advanced, life-saving therapies, but also on providing comprehensive solutions. Marken is continually growing and expanding to meet the complex and ever-changing needs of these and other industry therapies as they evolve. They are a committed and global supply chain partner for those organizations on the cutting edge of developing patient-centric treatments and therapies for diseases.
Sascha Sonnenberg has been with Marken since March 2011 and is the current Vice President Cell & Gene and CTS services, supporting Marken’s strategy for growth in the cell and gene industry. He is an active member of the APV Knowledge Group for Pharmaceutical Packaging and is engaged in the ISPE Community of Practice on Investigational Products. Sascha studied economics at the University of Kassel in the field of marketing and completed his MBA at the Kassel International Management School with an emphasis on international business and management