Mitigating Supply Chain Risk in Clinical Trials

A Business Insider article from March 2015 explores the impact Queen Elizabeth’s passing will have on Great Britain.¹ The author states that “The death of Queen Elizabeth will be the most disruptive event in Britain in the last 70 years.” The article goes on to detail exactly what will happen to the country as it works to recover from this uniformly tragic event. For example, the author states that “For at least 12 days… Britain will grind to a halt.” and “Whatever happens formally… Britain effectively ceases to function.” Additionally, the article points out that the British Monarch is the official head of state for several other countries, including Canada, Australia, and New Zealand. It is not unreasonable to anticipate that the Queen’s demise will also have a meaningful impact in these countries.

For the pharmaceutical industry, a significant amount of drug supporting clinical studies flows through the UK, both directly to clinical sites in the UK and for onward distribution to other countries (see Figure 1 below). Should there be a halt to normal business operation in the UK, the impact to clinical trials could be significant, leading to supply interruptions to potentially life altering clinical therapies. Additionally, because the patients this industry serve are at the core of everything it does, ensuring the supply of clinical drug during a time of crisis is a necessary moral and ethical action to take. To that end, the clinical drug supply team at Biogen, in conjunction with Brizzey, a clinical supply chain management company, developed a decision-making framework that integrates real-world signals with supply planning techniques to proactively reduce supply chain risk and avoid potential supply interruptions.

Project origin

In April 2010, the Eyjafjallajökull volcano erupted in Iceland. The resulting ash cloud wreaked havoc in Europe, resulting in significant and unprecedented interruptions to all modes of transportation. Air traffic was halted over much of the continent. The capacity of the road and rail transportation network was overloaded. At the same time, French rail workers went on strike. In the aftermath of the eruption and with the added challenge of the French strike, moving anything into or out of Europe became enormously challenging. The pace of commerce slowed and, in many cases, supply chains came to a standstill.

Although the 2010 eruption of Eyjafjallajökull resulted in a very challenging period for clinical supply managers, it did present a valuable learning opportunity. Four years later, in late August 2014, the tectonic plates under Iceland were shifting again: earthquakes were being observed in Iceland and, this time, the Bardarbunga volcano was threatening to erupt. Having narrowly avoided supply interruptions due to the Eyjafjallajökull volcano eruption, our team chose to react very differently in 2014 than it did in 2010.

As soon as news broke that the Bardarbunga volcano could erupt, our leadership team put into action a proactive response. First, working with the appropriate CRO partners, the team contacted the clinical trial sites to understand their in-clinic inventory positions. Then, based on the site inventory levels and the assessed potential supply interruption risk, manual shipments were raised to get all European site inventories back up to maximum levels. Additionally, the supply managers worked closely with the quality and distribution partners to prioritize any shipments going into or out of the UK distribution centers. In parallel, the team identified alternate shipping routes (e.g., directly from the US to Japan instead of to Japan via the UK) and contacted vendors to understand courier contingency plans and options. Ultimately, the Bardarbunga volcano did not erupt. However, our clinical drug supply team learned a lot from the exercise and decided to create a project to turn this one-off action into a robust methodology.

At the core of this project is a desire to maximize the action period before potential supply interruptions. The goal of this methodology is to proactively respond to the signals that may precede significant events with the potential to cause supply disruptions. The team believes that, by monitoring real-world information, precursor signals can be identified. Some examples of this principle are: An earthquake in Iceland may predict a volcano; rioting may lead to significant geopolitical unrest; the Queen of England being admitted to hospital may signal that her passing is near (see Figure 2).

A five-step approach was taken to create this methodology:

• The team explored the practice of failure modes and effect analysis (FMEA).

• Both a proactive and reactive response process was defined.

• Key tools and teams needed to support this process were identified.

• Connections to existing Biogen tools and teams were developed.

• The necessary tools and templates than connected all of these business processes together were built.

Failure modes and effects analysis

The first step of this project was to explore common risks to clinical supply chains through the use of FMEA, a systematic tool for evaluating potential risks to a product or project.² The team brainstormed and documented potential risks that might interrupt development and delivery of clinical supplies. For each risk, the team numerically scored the risk based on the following three factors:

• The severity of impact should the risk occur

• The likelihood of the risk occurring

• The ability of the team to detect the signal

Multiplying the number scores for each of the factors above, the team identified the highest priority risks to be addressed through proactive actions when possible.

Defining proactive and reactive response processes

After completing the FMEA analysis, the team developed a framework to guide the proactive and reactive response processes. The proactive process is centered on surveillance, risk assessment, leadership engagement and proactive actions, all of which provided a framework and risk assessment for updates to individual trial plans (see Figure 3 below). For example, drug supply managers aligned on necessary and important quality-focused actions, engaging quality and, if possible, reprioritizing the disposition/release schedules that might address studies or countries facing a potential risk that could interrupt supply. The team also built out supply actions, focused on assessing supply options, such as prioritizing/expediting shipments, executing site-to-site transfers (of supplies or patients). The reactive process is focused on warning and alarm, iterating between triage and response and followed up by recovery actions (see Figure 4 below).

In a time of crisis vendors will be trying to support all clients. The team also believe that, by having this proactive response, being in a constant state of “ready” and having our response plans already 80% developed, the supply mangers will gain a competitive advantage by A) responding to a disaster before it happens and B) being first in line when a disaster actually occurs. The proactive risk mitigation procedures the team created require trial-specific plans that need to be consolidated and prioritized into a single plan.

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Defining key tools and teams

To aid in the response and recovery efforts, the project team needed to establish action-oriented teams and build tools to allow the team to better plan for and respond to potential supply interruptions.

• First, and most importantly, the Early Action Response (EAR) Team was created. Its responsibility is to sift through various signals and data sources to highlight events and situations that may impact our supply chain. This activity is carried out by existing members staff. The EAR Team’s sorting efforts are enhanced by reports provided by the company’s global security team. Once these issues are identified-through our security team, monitoring news sites, weather information, social media and upcoming events-the EAR Team distributes information to a larger group for general awareness or action.

• A seasonal calendar was developed. This is an Outlook resource used to track and communicate upcoming events and potential impacts. The seasonal calendar is updated by the EAR Team and discussed during regularly scheduled meetings. This tool provides visibility to weather patterns, world holidays or major events and is intended to raise awareness of potential supply chain risks.

• A site geography tool was created. The tool allows for quick identification of sites located in a target region-where a risk event has occurred. It is used when the EAR Team dispatches an alert requiring action regarding an event posing supply risk in a certain geographic location. The tool is primarily used by the clinical supplies manager as a framework for subsequent discussions with stakeholders.

• An emergency contact for clinical sites tool was created, which serves as an escalation and hub-and-spoke communication pathway from clinical sites (through CROs) to the sponsor company and back out to sites. After initial notification of an event, the CRO business continuity team assesses impact to patients, active trials and personnel in affected region(s). This tool is used after initial assessment is made of the impact of event in particular region(s); CRO would notify the sponsor company of issues and next steps.

• Finally, an impact assessment matrix and decision tree was created. The matrix classifies events as A) high impact, short duration B) high impact, long duration C) low impact, short duration and D) low impact, long duration (see Figure 5). Once an event has been classified, a corresponding decision tree aids the crisis manager in formulating a proactive avoidance plan or a reactive recovery plan.

Exploration of existing Biogen tools and teams

A key part of this effort was to leverage existing tools and business processes.

• The team identified a database, developed and used by our clinical operations team, that stores information on the geography of our clinical site and which studies are running at those sites. The team chose to leverage this tool and repurpose it for our initiative. So now, in a time of crisis, supply mangers can determine, in a matter of minutes, the exact location of each site and the trial in which they are participating.

• The team agreed that all EAR Team updates would flow through a regularly scheduled (weekly) meeting between supply management leadership, internal/external quality, internal/external manufacturing and other support functions. The desire was to connect the EAR updates into an existing forum rather than creating a new meeting.

• A supply chain summary table was created, which was folded into the existing supply manager peer-review process: a regular, informal review of the supply chain and supply plans for our clinical programs. This template is intended to document the supply chain vendors used for a given study and alternative vendors that can be used in the event of a disaster.

Bringing it all together

The team developed a four-step rollout, implementation and training plan. The first step was to communicate the development of this proactive risk-monitoring plan to all of our stakeholders. The second step was training. Training included A) staging mock events to pressure test the methodology, B) including outside vendors and clinical operations and C) performing training in waves across all invested parties. The third step was implementing the methodology into our day-to-day business operations. The final step was garnering feedback and using it to drive continuous improvement. The team recognizes that this effort will be an evolution and expects to improve with each event.

In summary, partners Biogen and Brizzey believe that this decision-making framework, which integrates real-world signals with supply planning, will allow Biogen to proactively reduce supply chain risk. The supply management organization has a team in place that is monitoring data sources for signals to identify potential supply chain impacts. The companies have built a tool that gives line of sight to major geopolitical events or natural disasters that may have potential supply chain impact.

Chad Presher is Associate Director of Clinical Drug Supply, Biogen; Adam Sheriff is Senior Director of Clinical Drug Supply, Biogen; Lorna Briddick is managing Partner, Brizzey LLC

* The authors wish to thank Rob Pizzie of Brizzey LLC and a native son of the U.K. for his participation in the development of the process and construction of this manuscript. Thanks also to the members of the Biogen Clinical Drug Supply organization who participated in this project (Doug Meyer, Melissa Fortin, Bruce Chafee, Tala Kayyali, Meagan Ruffen, Paul Larochelle, Katie Vallone, Marissa Martinez del Campo, John Jordan, and Kate Woodcock).

References

1. Price, Rob. “This is What Happens When the Queen Dies.” Business Insider. Published online March 6, 2015, http://www.businessinsider.com/what-happens-when-queen-elizabeth-ii-dies-2015-3?r=UK&IR=T

2. Quality-One. “Failure Mode and Effects Analysis (FMEA)." http://quality-one.com/fmea/?gclid=CjwKEAjw8ZzHBRCUwrrV59XinXUSJADSTE5kj0sigU__P-NNaBK7uaHc8qjIbwDrA1-bpAFcUzDCQBoC6LTw_wcB