Very few pharmaceutical companies could claim a fully robust supply chain that can track the full data life cycle of their investigational medicinal product (IMP). In an evolving market, with the increasing complexity of Good Distribution Practice (GDP) and Good Clinical Practice (GCP) regulations (EU GDP Chapter 9; ICH GCP E6), this disparate data means that no sponsor can truly claim 100% visibility and regulatory compliance. Without this oversight, can responsible drug manufacturers assure patients that their products are safe to take? The honest answer is ‘not always’.

With regulations stipulating that manufacturers need to prove the quality and integrity of drug products, and, more specifically, that products must be maintained within specified temperature limits throughout the entire supply chain, current supply chain strategies show an incomplete picture and are insufficient proof of regulatory compliance.

The challenge

The vast majority of products in clinical trials today – investigative, comparator and companion – need to be maintained at a controlled temperature; this is a growing challenge for drug manufacturers. In 2016, 75% of the shipments that Almac Clinical Services managed required temperature controls – up from 25% just five years earlier. Typically, developing a supply chain strategy has been a complex process involving a cascading series of decisions. The usual steps include:

  • Acquiring the product’s stability data from the manufacturer. This will specify the required temperature range and any allowable excursions. Some products are allotted an ‘excursion budget’, meaning they may withstand multiple excursions up to a certain cumulative limit.
  • Identifying the challenges associated with the footprint of countries that will be involved in the trial; the shipping lanes needed; and the different storage facilities required.
  • Comparing the product’s requirements against the capabilities of facilities all along the distribution chain to ensure their ability to be in compliance.

It is a complex journey and, particularly in global clinical trials, every unique shipment makes its way to patients through an array of different storage and handling conditions, including a diverse range of phase-change shippers, temperature monitors, couriers and depots. Each mode of transport, period of storage and change of hands along the way has the potential to expose the packaged product to temperature changes. Even at the clinical site, different storage facilities and conditions make it harder to maintain control over the drug product, and holding all sites to a common standard is very difficult. To add to this complexity, when each of these different stages and locations report and store temperature data across multiple, unrelated databases, there is no complete oversight of the temperature data throughout the product life cycle, resulting in unrelated data silos across the entire supply chain (see below).

It is a complicated business just to address all of the known factors. But, of course, even with the best-laid plans, there is the potential for an unexpected event that can jeopardise the product’s condition. A shipment could be unloaded from an aircraft and sit in uncontrolled conditions for hours. Customs officials could open shipping containers and remove the temperature monitors. Traffic congestion between the airport and site can delay delivery until after a site is closed for a weekend. This list goes on.

So, as supply chain managers plan a product’s path, they must take into consideration the risks and costs associated with the different climates, timelines, and regulatory hurdles presented by different modes of transport (air, sea or land), shipping lanes, package options and storage locations, and must implement a suitable strategy to deal with them. This strategy must be rigorous enough to prove regulatory compliance and drug supply assurance to the patient, while also reducing the strain at sites and allowing improvements to be made in the future.

Data-driven solution

Advances in temperature-controlled shipping systems, courier services, airline infrastructure and services are all enabling significant improvements in temperature control during transit, with the best physical infrastructure for distribution providing the same robust performance and level of assurance to that of the temperature-controlled warehousing that the industry employs today. However, in the same way that the industry would not operate temperature-controlled warehousing without collecting and reviewing the data on a regular basis, so, too, should manufacturers be diligent with regard to the data that can be collected while the product moves throughout the clinical supply chain.

While this physical infrastructure has historically been the best practice approach for drug manufacturers, with increasing regulations in transit and storage, this is no longer solely sufficient to achieve compliance. The only way to prove this is to lead with a data-driven strategy, using a platform that provides a complete view of the physical supply chain, and facilitates robust data collection and analysis across a universal data repository. Moreover, the platform should be flexible in order to support a varied supply chain with numerous stakeholders; for example, insulated shipping systems, temperature monitors, distribution centres, couriers and clinical sites.

By consulting data on the end-to-end supply chain and each touchpoint of the products’ journey, in transit and at the clinical site, it is possible to adopt a proactive approach to distribution that drives improvements and regulatory compliance, lowering the risk of unplanned temperature excursions while providing controls for planned excursions – when products are intentionally removed from ideal conditions to allow processing. A platform that also integrates with interactive response technologies (IRT) will also support an automatic transfer of captured data on spoiled products, triggering an automatic resupply order to the clinical site.

Manufacturers can gain added assurance by working with a team of dedicated temperature experts who can support in-depth data analysis, creating an audit trail of each shipment, analysing problems and ultimately learning from and building on experience. For global trials, this requires having global staff available 24 hours a day, across different time zones. With this data-driven approach, drug manufacturers can create a better global supply chain with full assurance that their physical infrastructure is working and their product is safe to administer to the patient.

The increasing pressures of regulatory compliance are arguably felt most at the clinical sites that could be managing multiple protocols with various sponsors at any one time. Sites are now required to manage increasingly complex clinical trials and, in addition to caring for patients, clinical research associates (CRAs) are expected to complete a host of documentation and other tasks for each protocol, recording and reporting temperature readings being just one. Moreover, as part of the overall life cycle of data, temperature logs are often kept manually or, sometimes, not at all.

Storage compliance of IMP can also be challenging; for example, with validated refrigeration. With this burden comes the associated struggle for the sponsor to execute a successful sitelevel monitoring plan, which is almost always dependent on staff diligence and adherence to agreed expectations.

The answer lies in finding an auditable and GCP-compliant platform that can support and ease the burden on these sites and their staff, and facilitate excursion management and recording of storage temperature history. Combining that with adjudication staff who can provide an immediate response to reported excursions, make decisions about product viability and determine a course of action – especially if the situation will impact patient treatment – is the most suitable strategy for clinical site compliance.

100% visibility

In a constantly evolving market with increasingly stringent GDP and GCP regulations in place to protect the patient, as well as more complex drug products, manufacturers can no longer afford to take the risk of insufficient temperature management of their IMP during distribution and at the clinical site. The best supply chain strategy needs the physical and data components in order for a complete temperature history to be available. Unified on one platform and supported by a temperature expert team, this data-driven strategy will form the foundations for in-depth data tracking and analysis, driving decisions and improvements, as well as management of different stakeholders and the clinical sites. The next step in this evolution is to then extend this best practice to support medication stored at the patient’s home.

When the latest technology is employed as part of a comprehensive supply chain strategy, the product’s integrity is preserved for patients, compliance is demonstrated for regulators, and continuous process improvement is evident to sponsors and sites. Only this unified strategy can provide 100% visibility and regulatory compliance across the full product life cycle and, most importantly, assurance that the IMP is fit for patient administration.