Upholding product integrity is mission critical to protecting patients and achieving safe and compliant clinical trial outcomes. It also has a pivotal role in controlling study costs and promoting timely trial completion; both essential components for making breakthrough therapeutics available to patients sooner and maximising a sponsor’s return on investment. However, upholding product integrity is becoming increasingly challenging for sponsors dealing with complex biologics that demand stringent temperature control to maintain drug stability through each stage of the supply chain.
Mitigating the risks requires sponsors to implement preventative measures to both reduce the likelihood of excursions and maximise detectability. Increasingly, it also requires sponsors to embrace digital transformation: to replace existing manual approaches to temperature management with automation that has the potential to lower the likelihood of an excursion occurring, while increasing detectability and promoting fast and accurate adjudication. Integration of core supply chain technology – including forecasting, ERP, IRT and temperature management systems (TMS) – can promote end-to-end drug temperature data visibility and help mitigate risk.
Mitigating the Risk of Temperature Excursions 101
Before exploring the opportunities that system integration can present, it’s important to understand the fundamentals of mitigating the risk of temperature excursions. This starts with identifying the risk and outcomes if those risks are realised. If a drug is exposed to adverse temperatures, one of two scenarios will unfold. The excursion event will either be reported, or it won’t. Each presents its own ultimate risk.
If excursions occur and are reported, drugs are rejected, and the patient cannot be dosed and is possibly lost from the trial – increasing trial costs in both product rework and recruitment. Meanwhile, if excursions go unreported, the compromised drug remains available and patient safety hangs in the balance. Both scenarios can have a significant impact on the patient (their experience and their safety) and the trial; delaying timelines and introducing further cost.
A Preventative Approach
Key to mitigating the risks associated with each scenario is taking preventative action. It’s necessary to consider how the level of control sponsors have over their supply differs throughout the supply chain. Risk assessing each stage, from production line to patient administration, to understand what mitigations can be used and where (prior to study start-up) will facilitate fewer excursions and enhance detectability. The audited facilities of sponsors and CMOs represent a relatively low risk for temperature excursions. However, once temperature-sensitive supply begins its journey to sites and patients, the likelihood of temperature excursions increases, while detectability plumets. Drugs in transit are at the mercy of third parties, making it harder for sponsors to know if an excursion has occurred and, if it has, whether it has been appropriately reported in line with defined processes. This typical lack of visibility and control extends through global distribution to storage at clinical sites and within patients’ homes.
The question sponsors need to ask at this point is how visible are excursions that happen and what facilities will be responsible for reporting, and how? Whereas CMOs operate audited facilities with validated processes to identify and report excursions, processes are typically less robust further along the supply chain. The further from the sponsor products travel, the more difficult detectability becomes.