Interactive Response Technologies for IP Temperature Excursions

Q. How can interactive response technologies be used to manage investigational product temperature excursions?

A.Effective and efficient management of investigational product (IP) temperature excursions at each stage of the clinical supply chain is crucial to trial success. The increasingly global nature of clinical trials--and the supply chain that supports them--combined with IP manufacturing, packaging, labeling, and storage constraints, increases the importance of IP temperature excursion management to trial, program, and business success. In fact, a recent report predicted global healthcare cold-chain logistics spending to increase by 4% compound annual growth rate (CAGR) between 2012 and 2016, reaching $10.7 billion by 2017 (1).

• Shipping excursions

• Inappropriate storage conditions

• Fridge/freezer failure at depot or site

• Weather (recent examples including hurricanes Katrina and Sandy)

• Power failure

• Temperature monitoring system failures

• Other factors (such as inappropriate storage by subjects after allocation but prior to administration, or unexpected intervention by customs officials).

Effective temperature excursion management seeks to mitigate the impact of temperature excursions on trial execution in cost, time, and effort. This is accomplished by:

• Ensuring IP that has exceeded its exposure limits is not allocated to patients

• Preventing depot and site stock-outs related to IP temperature excursions

• Avoiding missed or extra subject clinic visits due to excursion related stock-outs

• Mitigating IP wastage and shipping costs

• Eliminating additional unplanned labeling/packaging of supplies due to IP temperature management issues.

Fundamental IRT excursion management approach
Interactive response technologies (IRT) systems have long been used to manage temperature excursions. Typical systems provide functionality for depots and sites to quarantine shipments or individual kits. This functionality prevents subsequent ordering of the affected product to a potential destination or allocation to subjects until IP viability can be confirmed. Another option may be configured to replace IP immediately, or only if the product is damaged. The shipment temperature-logging device is returned to the sponsor for analysis of excursion severity and duration against current stability data. Data loggers that provide downloadable human readable reports eliminate the need to send the device back to the sponsor for analysis. The IRT system can be configured to link individual data loggers to specific IP units in the shipment if required (where there are multiple loggers in a shipment). The output is simply uploaded to a portal with document-sharing capabilities. After IP usability is determined, a further IRT transaction allows the sponsor to release the IP for use or make it permanently unavailable.

Pros and cons
There are many advantages to this approach. It is a relatively straightforward process supported by standard IRT functionality and can be configured to replace IP immediately after the transaction.

There are, however, downsides to this methodology. It does not reduce adjudication cycle time or the time taken to render a decision on usability. It also carries the risk of increased stock-outs and subject resupply issues if IP is not immediately replaced after an excursion occurs. Finally, manual analysis of every excursion is still required before a decision on usability can be rendered.

In practice, it often becomes necessary to pre-emptively replace site IP stock to allow enrollment and resupply of existing subjects to continue. This replacement of stock places further strains on the supply chain in a number of ways:

• Reducing supply chain flexibility as relatively more IP is transferred to sites

• Increasing potential for site stock-outs

• Creating additional overage requirements to compensate for damaged product or delays in usability decisions

• Increasing required effort to gather and analyze temperature excursion data

• Increasing likelihood of additional shipments  

• Impacting site storage constraints due to the need to store quarantined IP until usability is confirmed

• Potentially increasing drug wasted if additional orders are required and the site becomes overstocked in relation to the number of patients

• Affecting overall accountability and reconciliation activities at each impacted location.

So how can IRT systems further automate the process to reduce cycle time, cost, and effort? IRT solutions can actually be designed to automate the adjudication of IP usability. To facilitate this, the IRT must ‘know’ the IP’s storage and excursion parameters. These values can be stored, in most cases, at the IP ‘pack type’ level or ‘packaged lot’ level. Parameters can be pre-selected and stored in the IRT database or updated by an IRT transaction, providing an intuitive modality for data entry, or supplied through data integration if required.

An IRT excursion transaction then allows users to record excursion severity, maximum temperature deviation, and duration. The IRT system will then automatically adjudicate IP usability based on excursion details and parameters previously entered into the system. Decisions can be rendered immediately on IP usability, saving time and avoiding unnecessary additional shipments due to temperature excursion.  Reports provide additional visibility into individual and cumulative excursion details. Additionally, the IRT can be programed to account for cumulative excursions against specific IP units. Excursion reasons and frequency of excursions (by location) can also be reported and tracked for enhanced visibility and metrics.

IRT provides flexible options for the sponsor to manage IP temperature excursions effectively and efficiently. These options include management of shipment and IP unit status, integration with distribution management systems, and inclusion of advanced functionality to automatically adjudicate IP usability. Success factors include careful system design (including impact assessment to other systems/processes), implementation, and adequate reporting of excursion data that includes frequency and distribution. Training delivery, reporting, and compliance monitoring are also important key success factors.

References
1. IMARC, Global Healthcare Cold Chain Logistics Market Report & Forecast: 2012-2017 (November 2012), www.imarcgroup.com/healthcare-cold-chain-logistics-market.
2. FDA, Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance, Section 5.13.2 (Rockville, Md, April 1996), www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073122.pdf.
3. C. Milligan, E. Sadler-Williams, and K. Gram, Pharmaceutical Engineering Vol. 3, No 4 (July 2013).