By Ravi Nalliah, CEO, and Tim Cleary, associate director, TrakCel
Orchestrating a modern cell and gene therapy supply chain involves enormous complexity. As a result, simplicity and standardization — in effect, plug and play — is demanded by the industry, especially for IT systems that track and guide personalized therapies from collection to infusion. However, there are often overlooked variations within the cell and gene therapy supply chain that inject additional complexity and obstacles to this idealized one-size-fits-all solution. While the necessity for tracking is now well known in the industry, there are lesser-known aspects that need consideration. In this article, we’ll examine four of these and explore ways to minimize or overcome these obstacles.
1. Variation In Technology, Starting Materials, And Collection
It’s not often appreciated by the wider market how diverse the cell and gene therapy field is, specifically in terms of technology, starting materials, and sample collection processes. Current products in development could be classified as autologous or allogeneic. However, even these terms don’t always neatly fit, with, for example, patient-specific allogeneic therapies. Then there are separations in terms of the technology used, with a myriad of different approaches and tools being developed to leverage the immune system to target and eliminate offending cells. There are, for example, hematopoietic cells, endothelial cells, mesenchymal stem cells, T cells, NK (natural killer) cells, and dendritic cells. To obtain specific targeted cells, there is a need to identify and collect the right starting material. Some examples of these include skin (fibroblast), tumor tissue, whole blood, apheresis/leukapheresis and bone marrow. Further differentiation of product types can be done based on disease indication, as the timing of treatment itself can vary greatly. Some will be treated as soon as possible, while others require careful orchestration with adjacent therapeutic regimes or even organ transplant.
Systematically, this variability in technology, starting materials, and collection procedures present a significant obstacle to a simplified orchestration solution. Looking solely at starting materials, each potentially has unique collection cycles, processes, shipping/temperature/storage requirements, and even healthcare professionals completing the collection; requiring rules and structures built into the software specific to that product. Autologous immunotherapy products may appear similar at a high level, but they only bear a passing resemblance at a detailed workflow level.
2. Variation In Patient Scheduling And Managing Capacity
Scheduling patients in a timely and efficient manner is vital at commercial scale. As many know, this is not an easy task in an extensive, highly constrained cell and gene therapy supply chain. In addition to the differences in starting material and products discussed above, a company’s overall approach to managing collection, logistics, and manufacturing resources also adds variability and further influences how software solutions are developed. Products may have unique scheduling constraints to support timing of preconditioning or parallel treatments, as well as shipping temperature / expiration requirements (fresh or frozen). For example, Dendreon’s Provenge product shipped fresh on the inbound side with an expiration of 18 hours post-collection, but more recent fresh products are validated for 72 hours. When using external collection centers to get apheresis samples, a company must decide how to integrate and schedule against this additional resource. A common strategy is to contractually reserve apheresis capacity by date/time/site. This makes scheduling easier and quicker for the patient as they can get a finalized schedule at the time of request. The disadvantage of this approach is it can be expensive, inefficient, and challenging to align reserved capacity with geographic demand. The alternative is to contact to a collection resource each time a tentative schedule is formed and request confirmation, but this adds additional delays and results in a poor customer experience.
Manufacturing is another element differing from one company to another. It can be done in-house or contracted out, to one facility or many, nationally or internationally. The manufacturing process itself will be entirely product-specific. If a company has multiple facilities, even the process of receiving drug product at one facility could differ from another. In addition, the suite configuration, quantity of equipment, and resources will vary, resulting in different capacity models that the orchestration system should recognize. For some indications, drug product is released once all release assays are complete, while others have a conditional release, allowing the delivery of the drug product to the clinical site while lengthy assays — such as sterility — are still awaiting completion. Companies must maintain capacity for available resources and schedule patients from collection to treatment. However, no two companies will have identical scheduling requirements.
3. Variation In User Groups And In-System Notifications
Another important and complex aspect in a cell and gene therapy supply chain lies in the user groups and in-system notifications. In our experience, every company could have different user groups that are responsible for performing specific tasks. Individuals responsible for tasks like managing capacity, scheduling patients, uploading documents, and ordering couriers can vary in the supply chain. There is no set, consistent model that can be easily adopted without custom configuration. Especially during clinical development, people undertake many roles, with some functions either understaffed or yet to be initiated (e.g., logistics, case managers, etc.). Workflows for these younger companies may be more malleable but as they mature, legacy operating procedures become more and more challenging to bend. Beyond workflows, how the system notifies involved parties and orchestrates the characters internally varies with each company. Basic rules can be created to prompt alerts for important delays, such as a late courier or treatment failure, but the specific timing and triggers will be unique.
4. Variation In Clinical Sites
An astute understanding of a clinical site is critical to configure a cell orchestration platform. Many processes that work flawlessly at one site may not work with others. One often-overlooked part of the supply cycle is the physical touchpoints at clinical sites. Basic questions to ask are: What is the physical layouts of the pharmacy in relation to the cell therapy lab and the point of administration? How far apart are those places? They could be in close proximity or on a different campus requiring an additional distribution step. Furthermore, where does a clinical site store the frozen drug product? Is it held in the cryoshipper or moved to temporary storage until infusion? Building a systems that perfectly aligns workflows to a few clinical sites may not scale due to the variability in how clinical sites operate. For a clinical site to adopt a new system it must simplify procedures to facilitate adoption. It is imperative to understand how these sites operate to design a system that will fulfill unmet needs and streamline clinical activities.
These are a few examples of the lesser-known challenges that need to be addressed within the fast-moving and evolving cell therapy field. We are working closely with the National Health Service in the UK to create a single and coherent model to address challenges such as these by modelling processes at centers of excellence with different therapeutic products. This aims to standardize processes across multiple products and make it easier for the providers to administer these curative therapies to the wider population.
About The Authors:
Ravi Nalliah is CEO at TrakCel, a clinical orchestration platform company designed to efficiently safeguard patients and orchestrate processes across regenerative and cell-based therapies. Prior to joining TrakCel, he was finance director at PCI Services Inc, a provider of drug development services. Nalliah was also a key member of the team that, in 2010, led the management buyout of Biotec Services International, a clinical trial services and supply group specializing in clinical trial services for Phase 1 to 4 trials. Ravi is a qualified chartered accountant and also holds a B.Sc. in biochemistry and molecular biology. You can reach him at email@example.com.
Tim Cleary is associate director of customer solutions at TrakCel. Prior to joining the company, he worked in the cell and gene and consumer DNA industries for eight years, primarily focused on cold chain logistics and supply chain. The majority of that time was spent at Dendreon, soon after the company gained FDA approval for the first CAR T-cell therapy for prostate cancer. Cleary left Dendreon in 2015 for Arivale, where he led the design of and implementation of the company’s supply chain. Cleary holds a B.S. in global supply and operations management from the University of South Carolina. You can reach him at firstname.lastname@example.org.