Got a robust process for managing site storage temperature compliance? This sponsor thought they did too…

Picture the scene, you’re running a clinical trial. It’s going well. The supply chain’s optimised, enrollment is exceeding projections and study results are looking promising. All is going well.

Cut to an FDA clinical site audit. While reviewing the site storage temperature logs, the auditor frowns – their demeanour shifts. They’ve just uncovered 12 excursions. Excursions that have been left unreported for a period of two years. Excursions that could have compromised drug products, patient safety and research validity.

You’re stunned. You ask, “how could this happen?” Afterall, you have a robust process to manage site compliance, right? As you piece together where it went wrong and uncover the extent of the problem, one thing’s clear: this can’t happen again.

So what went wrong?

This story isn’t a work of fiction. It happened in the real world. But how did multiple temperature excursions go unreported for two years? Well, like most sponsors, this large pharma company utilised a manual process to manage site compliance.

While Almac manages adjudication for transit and site-based excursions, via the TempEZ platform, the CRO was responsible for ensuring sites complied with the approved reporting process. Despite regular visits, the CRA failed to detect the 12 unreported excursions.

Factors that contributed to this outcome included:

• Retrospective review – the CRA would visit sites periodically and review compliance retrospectively, making it difficult to catch instances of non-compliance in a timely manner.
• Broad remit – the CRA was responsible for more than just temperature management and would divide their time and focus at clinical sites between multiple functions and processes. This made it easier for the unreported excursions to go unnoticed for so long.

Sarah McAliskey, Temperature Services Manager at Almac Clinical Services, explains: “As you move through the clinical supply chain, the likelihood of a temperature excursion occurring increases, while the detectability plumets. Site storage compliance is a real blind spot for sponsors and demands proactive management to mitigate risk and ensure site excursions are adjudicated in a timely manner.

“Unfortunately, for this client, the flaws in their manual approach caused unreported excursions to go unnoticed for years, which could have resulted in study drug being administered to a patient that was stored outside of the labelled conditions. Not only did this sponsor need to quickly establish if drugs that should have been rejected were inadvertently assigned to patients, they needed to ensure it couldn’t happen again.”

Uncovering the truth

Under pressure from the FDA, the sponsor reported the 12 missed excursions to Almac, who prioritised the project and fast-tracked the review process. A team of dedicated temperature experts meticulously sifted through a significant amount of data . This included looking at kits in timeline order to assess the cumulative impact and whether they had been subject to more than one excursion. Thorough, expert adjudication was completed in just 24 hours and determined that no kits involved in the unreported excursion events were classed as needing to be rejected.

Although it demanded urgent attention and significant resource, the sponsor was able to demonstrate that the safety and efficacy of all compromised supplies was upheld. However, this scenario could have unfolded very differently, with significant patient risk and regulatory impact.

Picking a better path

Determined to prevent a repeat occurrence, the sponsor instructed Almac to take over site compliance management. This would involve dedicated focus and monthly reviews of site temperature logs – drastically reducing the window of risk for excursions to occur and go unreported. Temperature data logs would also be stored in the Site Compliance module of TempEZ, increasing visibility of temperature data and improving the chances of detecting unreported site storage excursions faster, while minimising risk to patients.

Putting patients first

Sarah comments: “We proactively collect temperature data each month and harnesses the latest technology to create better visibility over site compliance, track performance, assess trends and flag issues. Because we have eyes on the data sooner, we can act faster to increase compliance and ensure excursions are identified and reported quickly and effectively.

“This new approach will help to avoid any regulatory fallout following site audits in the future and ensure patient safety remains at the heart of this sponsor’s clinical trial.”

The lesson from this cautionary tale?

You may think you have a robust process for managing site compliance for your temperature sensitive supplies but without a dedicated, pro-active process for keeping sites in check, you too could fall victim to site-based temperature excursions slipping through the cracks.

Need to get on top of site compliance? Speak to us.