Rising complexities of randomization and trial supply management in small, specialized patient populations
Due to smaller patient populations, rare disease patients can be scattered globally for any given trial. This complexity alone is a burden to patients that may not have local treatment options and introduces supply chain logistical challenges to the manufacturers.
Rare disease trials typically involve biologics, or large molecule drugs or increasingly peptides. These newer drugs often don’t have the manufacturing schedule or predictable shelf-live that many of the smaller molecule drugs. Many of these drugs require special handling, temperature control and quick turn-around due to short shelf lives. Because of the nature of the drug and sometimes the severity of the disease, treatment may need to begin within 24 hours of enrollment. Enrollment itself may be unpredictable so the supply chain must be robust enough to support patients when and where they enroll, globally. Given that small patient populations also equate to smaller dose quantities, the importance of an air-tight supply chain is heightened.
To address these challenges, it is crucial for manufacturers to have a robust IRT or randomization and trial supply management (RTSM) system in place.
What are the essential IRT capabilities to support rare disease trials?
1. Complex site initiation and randomization capabilities.
Given that rare disease patients may travel significant distances to participate in a study, the randomization and trial supply management system needs to be ready at all times; because, asking the patient to return isn’t a reasonable option given the effort that they put forth in getting to this point in the study. Adding to the complexity is the drug delivery devices themselves, as some rare products require up to 40 preparation steps prior to administration to the patient.
To ensure randomization can happen at short-notice, in some cases, manufacturers may pre-initiate sites to enable them to finish essential documents and enroll the patient within a 24-hour period. The IRT supports this by being able to stage drug at a significant number of depots around the world so the drug could be overnighted to sites when activated. The IRT systems also need to be able to manage the supplies at both the sites and the depots effectively.2. Flexibility built into the system
Many traditional IRTs are rigid and require added time and resources to allow for adjustments during the study. A modern, flexible IRT is needed to quickly adapt to changes in patient population, enrollment, site location, etc. For example, as patients are dispersed around the globe many will need to travel significantly to get to the study sites. If by chance a new site opens that is more convenient for the patient, the IRT must be able to easily transfer the patient and all their resulting supply needs. Another complexity that requires flexibility is the adding or dropping of countries within the study. Switching countries may mean varying supply regulations and even supported languages.3. Resupply capabilities and supply chain scenario planning
IRT systems are crucial to the overall management of supplies from receipt of the depot to destruction per the manufacturer's instruction. It is becoming an increasingly valuable component of a study's supply chain.
Biologics present many supply logistics challenges from production to distribution and storage. While all supply chain management in the clinical realm has its challenges, biologics manufacturing has even more complexities, including a higher incidence of production issues. The drugs that do make it to the sites have a short shelf-life, sometimes only a few months. This puts an additional burden on the IRT system to ensure that patients are not using any product beyond their intended shelf-life date. To make supply management even more challenging, many of the new supplies don’t have established shelf-life dates and are submitted to site on a stability protocol. At any specific pull-point, the product may be in or trending out of specifications. If it is trending out of specifications, the IRT system needs to quickly adapt to ensure that study drug is returned per the manufacturer’s instructions.
Another supply consideration is linked to enrollment projections. If enrollment outperforms predictions by even an additional 500+ patients, with a rare disease trial, this could double capacity. The complexity of the product may not allow for the speed of turnaround that would be needed. A robust IRT should have advanced supply forecasting and scenario planning functionality.4. Temperature control management
Biologics need to be temperature controlled during transit and storage. Therefore, a robust IRT is needed that reacts quickly to any shipment that has been identified by the site, and confirmed by the sponsor, as being outside of the product’s storage condition.
5. Online drug accountability, returns and destruction
A robust IRT system is needed to track these drugs through a very complex and evolving supply chain. Sponsors are using drug dispensing records from the IRT, from receipt to destruction, to strengthen compliance capabilities in the event the site is audited.
Additionally, tracking the drug may not stop after the close of the clinical trials and the approval of the drug. Once the drug is approved, you may end up with a post-commitment trial. A robust IRT should be able to handle the switch from investigational to marketed drug. The IRT is a critical component to ensuring you have an air-tight supply chain for your rare disease trial. The system needs to handle complex randomization, have the flexibility to adjust with the evolving trial scope and offer significant capabilities in resupply and supply scenario planning.
This article was previously published in Applied Clinical Trials' eBook on Clinical Trials for Rare Diseases.
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