Immuno-oncology (I-O) studies are very specific to the patient being treated, and this individualization directly affects the handling, workflow, and shipment of the drug product and patient specimens.
“For example, for most cell-based therapies, only those cells that are being processed for a patient can be used for that same patient,” explained Dr. Chris Learn, program manager, oncology and hematology at Icon.
This means the therapy cannot be replaced with an existing, quality controlled supply if lost or damaged – as opposed to a traditional oncology study in which one specific drug is used across various patients.
Additionally, because the drug product is labile and unstable, I-O trials typically require many supporting players in the supply chain.
“Close coordination and communication across all stakeholders is a requirement, as one misstep anywhere in the supply chain may result in delay or permanent loss of patient sample, along with opportunity to treat,” Learn told us.
Adding to the complexity are numerous handoffs of the drug product and patient samples.
For the purposes of cellular manufacture, Learn said blood product transport in I-O trials typically involves 10 or more steps, including collection and shipment of the unprocessed drug product to a cell therapy laboratory for processing, manipulation, production, quality control, and QP release. The product must then be frozen before shipment back to the trial site.
“To support such logistics, a team of couriers, vendors, site team members, and sponsor personnel are involved in the various steps to ensure chain of custody and chain of identity at all times,” explained Learn.
While the process also is supported by systems such as interactive voice response (IVRS) to monitor and manage patient enrollments, Learn said manual tracking has been the primary system for control and compliance of I-O logistics.
“As these types of trials elaborate over time, there will be effort to reduce manual tracking in preference for automation,” he added, “However, for now, manual tracking ensures the most timely follow up and delivery of drug product.”
Additional requirements: Companion diagnostics, GMOs
To participate in an I-O clinical trial, patients must be prescreened for a genomic profile or expression of a particular receptor, which Learn said adds logistical complexity in terms of the patient work up.
“Compliance with standards, for example where companion diagnostics are in development, needs to be taken into account,” he added, noting that patient management also is a factor, “not least because screen fail rates can be higher.”
Also to be considered because of the personalized nature of I-O therapies are genetically modified organism (GMO) requirements, which industry groups, such as the Alliance for Regenerative Medicine (ARM) have met with concern.
According to ARM, the GMO application and clinical trial approval (CTA) process in some European Union (EU) member states places a “significant burden” on gene therapy medicinal product (GTMP) clinical trials, ultimately delaying patient access to “potentially transformative medicines.”
Learn explained, “Most competent authorities and regulatory agencies require that the patient pathway to treatment is mapped out prior to first patient activities to ensure that process, form, and function of the supply chain are validated.
“This cannot happen without detailed step-by-step analysis of the logistics path your protocol will take.”