April 11, 2019 PAO-M04-19-CL-002
Cell and gene therapies make up the advanced therapeutic medicinal products (ATMPs) market. Like conventional pharmaceutical supply chains, the ATMP supply chain consists of suppliers, manufacturers and clinical teams, but the cell and gene therapy supply chain introduces one additional unique component: the patient. Factoring in the patient places added pressure on the supply chain and requires companies to create logistics platforms that connect therapies with patients at both clinical and commercial scales.1
The process requires supply chain stakeholders to identify potential challenges early in the cycle to ensure that the distribution channel is robust and efficient. Particular attention must be paid to demand cycles, short delivery windows, storage and temperature requirements, track and trace and the myriad regulations governing the storage, handling and transport of these advanced therapies.
The global cell and gene therapy market is projected to exceed $35.4 billion in 2026, up from $6 million in 2017.2 And while only three such therapies have been approved for sale to date, departing U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb expects the agency to approve anywhere from 10 to 20 new cell and gene therapy products a year by 2025.3 The unique logistics challenges for ATMPs reflect the fact that cell and gene therapies are typically developed for specific, small patient populations. Predicting the demand cycle can be daunting for supply chain members, but they should work together to identify the patient population, location of manufacturing sites, the geographic areas of the clinical studies and the treatment sites for final drug delivery to patients.
These therapies are shipped “fresh” to provide better cell viability, creating a timing issue relative to the products’ end of validation (ranging from hours to a couple of days). This means that the shipping window is constrained by the duration of time that the cells remain active. The restricted viability demands that the therapy be collected/distributed within a certain distance from the manufacturing center; therefore, multiple manufacturing sites are necessary.1 Providers with larger networks are able to provide a higher degree of customization to address the unique needs of a given therapy and its specific supply chain.
In addition to strategically placed manufacturing sites, storage locations are as important to a strong supply chain. With autologous therapies, the patient and location are known from the outset, making distribution decisions more concrete. However, allogeneic therapies may be distributed to patients across a wide geographic area, and, often, the point of care for a commercial allogeneic therapy is in a different location than the clinical trials sites. This poses the challenge of determining where to place product inventory and distribution channels for the most efficient delivery, as well as determining the delivery models, including modes of transportation. A central challenge is delivering the final therapies to patients — given the complexities of the supply chain and the short window of viability of these products — in a form that is easy to administer to patients and without placing undue burdens on patients with regard to timing and location of administration.
There are also temperature constraints associated with cell and gene therapies, which require an even greater degree of temperature control than conventional biologics. Temperature must be maintained while in transport to ensure that the therapies retain their viability and potency. Thus, protecting them from extreme conditions and adverse temperatures is critical. The temperature can range from ambient to cryogenic to frozen, so it is important to define and precisely maintain the temperature control requirements throughout the supply chain.4
People are an essential part of the cell and gene therapy supply chain. Specifically, cell therapies involve administering healthy, living cells into a patient. Those cells either originate in the patient ultimately receiving the therapy (in the case of autologous therapies) or from another individual (for allogeneic therapies). For autologous therapies, the patient marks the beginning and end of the supply chain. Gene therapy involves modifying gene expression to repair abnormal genes via the therapeutic delivery of targeted nucleic acid constructs, rather than the infusion of live cells. As such, the supply chain itself is less complex than for cell-based therapies, but there are analogous traceability requirements for these therapies.5
The challenge with both therapies is that a therapy must not be administered to the wrong person; if that happens, the results could be catastrophic. Thus, a chain of custody is paramount, as the therapy changes hands among supply chain participants. The stakeholders of a cell and gene therapy supply chain are interdependent and must communicate and share data to provide transparency along the channel, while also assuring that sensitive patient data is appropriately protected.
Both the FDA and the Office of Biotechnology Activities at the National Institutes of Health maintain oversight of cell and gene therapies in the United States.6 Gene therapy protocols are reviewed by the Recombinant DNA Advisory Committee (RAC). To conform to FDA requirements, manufacturers should provide information about the supply chain to ensure the quality and safety of the final therapy product. To add to the complexity, each U.S. state requires a pharmaceutical distribution license,7 however, applying for these licenses can be costly and time-consuming. Globally, manufacturers and distributors need to conform to unique regulations in their respective countries, such as China, Europe, Singapore and Canada.
It is critical for logistics providers in this space to respond to these challenges by shifting their logistics decisions to the front of the supply chain. One such approach is logistics by design (LbD),8 which identifies risks and creates a distribution channel that guarantees the right therapy reaches the right patient at the right time –– either at the clinical or commercial scale. An LbD approach requires a collaborative effort among all supply chain stakeholders, appropriately located manufacturing and distribution capabilities and requires the ability to scale from clinical to commercial distribution.
Yourway is an integrated biopharmaceutical supply chain solutions provider that makes those front-end decisions and collaborates with stakeholders. Yourway’s full range of services for cell and gene therapy distribution includes primary and secondary clinical packaging, temperature-controlled logistics, storage and distribution services for the global pharmaceutical and biotech industries. The logistics experts at Yourway understand the complexities of the supply chain for ATMPs, have access to the necessary innovative technology needed for temperature control of these products, and manage an agile and responsive network that can ensure on-time and on-spec delivery of cell and gene therapies to the patients who need them.
Fiona has been with Yourway since 2015. As Vice President of Client Services, she has wide-ranging responsibility for aligning people and systems across the organization to keep projects moving forward and advance corporate objectives. Fiona also leads a number of strategic growth efforts to expand Yourway’s customer base and increase capacity utilization.