Quarantines, Complaints, Temperature Excursions & Other Debacles: Mitigating the Impact of Clinical Supply Disruption

By Steve Sinclair

Managing through Clinical Supply Disruption

While the best way to avoid clinical supply disruption is through careful planning and setting up a robust supply chain, the reality is that eventually something goes wrong. This happens to even the most carefully planned supply chains. Taking an approach that prioritizes addressing short-term impact first and then quickly addresses longer-term implications can guide you to an effective response.

There are degrees of severity and urgency to supply disruptions. A short-duration temperature excursion caused by a site employee leaving a refrigerator open too long usually has less impact than quarantining an entire lot at a depot. A single functional group can clear up some occurrences, while other instances require rapid cross-functional teamwork. The faster you stabilize the supply chain, the better.

Minimizing Patient Impact is the Top Priority

Considering your response ahead of time can help you address issues effectively when problems arise.  While no one wants to solely be reactive, the first priority needs to be avoiding patient impact. Considering implications on patient visits next month is important, but it is less critical than the patient who is currently at the clinical site and the patient who is scheduled for a visit tomorrow. Work through supply chain disruption by looking at the short-term impact first and then expanding your view over longer time horizons. We encourage our clients to address disruptions in the following sequence:

1. Take immediate actions: Evaluate patient impact and perform damage control to limit additional impact. Review upcoming patient visits and verify that the appropriate transactions are made in the IRT to prevent dispensing the affected drug. Adjust supply settings or shipping schedules appropriately (i.e., if a site’s refrigerator is broken and causes a temperature excursion, do not immediately trigger a replacement shipment that they also cannot store. If a lot has been recalled entirely, confirm that it will not be pulled into new orders).
2. Make near-term adjustments: Evaluate additional inventory availability at the depot and lead times to support a replacement shipment. Review stability data to determine if you can still use the material after evaluation. Determine whether you can reschedule upcoming patient visits without risking patient safety, causing undue inconvenience to the patient, or deviating from the protocol visit windows.
3. Update longer-term supply strategies & plans: Adjust batch production or packaging and labeling schedules. Accelerate or decelerate depot resupply shipments for different lots. Revise enrollment timing.

Field Example #1: Clinical Supply Disruption at a Single Site

Temperature excursions are one of the most common causes of drug quarantine though the impact may vary widely. In a recent client engagement, a site reported a temperature excursion that initially appeared as if someone had accidentally reported the temperature in Fahrenheit instead of Celsius – the log showed a peak temperature of 34.4° C for drug that should be kept between 2-8° C. Based on the site location and time of year, it seemed unlikely that the reading was accurate, so we proceeded cautiously.

First, we checked the patient visit schedule in the IRT and were relieved to find that no patient visits were scheduled for several weeks. However, there was still a chance for unscheduled visits in the protocol, so we verified that the suspect material was properly quarantined in the system.

Satisfied with this immediate triage, we then reached out to the site to investigate. The refrigerator had indeed catastrophically malfunctioned. 34.4°C was in fact the true temperature reached inside, and the drug was hot to the touch when moved to a second fridge. While the confirmation of additional storage capacity allowed for the possibility of resupply, we wanted to avoid wasting the quarantined drug if it was still usable. This product had considerable ambient temperature stability, so we reached out to Quality to check if higher temperature stability was known.  It turned out there was stability data supporting up to 40° C, so the material was acceptable for use with no patient impact or need for extra shipments.

Field Example #2: Clinical Supply Disruption across a Global Study

At the other end of the complexity scale, we recently experienced a situation with a global study where several factors coincided to create a potentially critical shortage. A resupply shipment to an international depot arrived without temperature monitors, while the existing product lot in the field had barely a month left on its labeled expiry and the lot staged to replace that expiring material was quarantined due to a product complaint. This disruption had the potential to impact 24 sites and four depots across six countries with more than 100 patient visits scheduled within one month of the existing lot’s expiry. Also, our lead times for depot replenishment were just about one month.

The resolution required a cross-functional team effort involving Quality, Clinical Operations, and Clinical Supply working closely together. First, we focused on the immediate needs – prioritizing shipments to sites that had active patients and pausing new patient screening to avoid increasing demand.

Then, to further conserve the existing inventory, we adjusted the IRT settings to reduce site buffer stocks and free up as much inventory as possible at the depots. Clinical Operations accelerated patient visits earlier into the visit windows to make as much use of the available material as possible before expiry. Clinical Supply worked to keep the sites stocked just-in-time for each visit, while Quality and Clinical Operations coordinated expiry overlabeling at the sites themselves to extend the useful life of the existing material where possible. Shifting attention to the replacement lot, we also notified the for our European depot, who were able to provide an expedited release.

With near-term plans coming together, we examined longer-term implications. Pausing patient screening meant we needed to revise enrollment projections and create a new demand plan. We accelerated the next packaging and labeling runs to make up for lost material and consolidated the remaining expiring lot at a depot that could perform expiry update labeling.

Despite the complex global supply network and a huge number of moving parts, we avoided any impact on patients. By careful management of the usable supply and superb teamwork from all parties, we stretched the dwindling supply out long enough to cover study needs until new material was introduced.

Key Takeaways

• Even the most carefully planned clinical supply chain can experience problems that may cause supply disruptions and impact patients.
• Some clinical supply chain disruptions are easy for the Supply Manager to resolve quickly by adjusting IRT settings with information from peers in Quality, Clinical Operations and the sites, shared live or by exchanging a few emails. More complex situations, however, will require working actively across functions and with external partners such as the CRO or CMO to fully address issues.
• Focus first on triaging the immediate patient impact and then on addressing longer time horizons. Prioritize the urgent while balancing the long-term impact.
• Patient safety and reducing disruption to trial operations should be the main priority when considering mitigation actions.

For help avoiding clinical supply chain disruptions and general clinical supply chain management support, contact the Converge team at info@convergeconsulting.com today.