No matter what you may think about the United Kingdom’s plans to leave the European Union, there is one aspect that bears no controversy: Brexit will have a major impact on the pharmaceutical and biopharmaceutical industry worldwide, and there is no uncertainty that all participants in the supply chain for investigational medicinal products (IMPs) will need to prepare to meet the impending challenges. Any company with existing facilities in the UK, regardless of where it is headquartered—U.S. included—will need to make significant adjustments in its operations and contractual agreements.
The need for supply chain continuity
Most sponsors rely heavily on contract manufacturing organizations (CMOs) to pack, label and, more importantly, distribute IMPs from a depot. In most circumstances, the shipment arrives at the clinical site one business day after dispatch. This rapid delivery is key to the resupply strategy for current clinical trial practices, and will be essential for business continuity when Brexit becomes reality.
What we do—and don’t—know now
To summarize briefly, the UK and EU will negotiate terms for the split by March 2019. While a great deal is unresolved at this point, the European Medicines Agency (EMA) has provided strong guidance to give marketing authorization holders of centrally authorized medicinal products some initial direction. According to guidelines issued jointly by the EMA and the European Commission, the UK will become a “third country” beginning March 30, 2019. This has significant repercussions relative to the manufacturing facilities, batch release sites, and qualified persons (QPs) currently located in the UK:
- Beginning March 30, 2019, medicinal products manufactured in the UK will be considered by countries within the EU as imported products. The marketing authorization holder will therefore need to specify an authorized importer established in the European Economic Area (EEA), and a control site where each production batch can undergo a full quantitative analysis to ensure its quality.
- For centrally authorized medicinal products, the marketing authorization holder will need to change the location of the current UK-based site of batch control to a location established in the EEA, and submit the corresponding variation.
- The EMA has made clear the expectation that batch certification will be required within the EU. As of March 30, 2019, the QP, who is legally responsible for certifying that each batch meets EU requirements, will need to reside and carry out his or her tasks in a member state of the EEA. The QP must either change residence, or a new QP in the EEA must be appointed.
While this guidance is specific to commercial releases, it is a strong indicator of intent for IMPs. Although it is possible that some special arrangements will be made between the UK and the EU for IMPs—a Mutual Recognition Agreement, for example—the movement of supplies between the UK and the EU will be far more challenging than it is today. Tax and import duties will almost certainly apply, a matter that has yet to be determined.
Your own impact assessment
Notwithstanding the many unanswered questions, we do know enough to enable companies to begin assessing their own circumstances and the potential impact now. Consider the following contingencies:
- Is the UK your current point of batch release to the EU? If so, do you have, or plan to have, study sites in the EU? In that case, you will need to make plans to transfer release from the current UK-based site to a location in the EEA, and submit an amendment to your clinical trial authorization.
- Is the UK the current location of your QP? If so, you will need to make plans for that person to relocate to the EU, or to appoint a new QP named on an appropriate licence for a facility based in a member state of the EEA.
- If your current point of batch release to the EU is not in the UK, but you have, or plan to have, study sites in the UK, the way ahead is less clear. But you should expect a potential increase in tax and duty expense, alongside increased costs for UK-specific release if that should be required. The post-Brexit GMP import process into the UK remains to be defined.
These are daunting prospects, and complicating matters considerably is the current demand on resources—both facilities and people. The fact is that a sizable proportion of available QPs in the EU are presently associated with facilities in the UK, which will very likely result in a severe shortage and considerable competition for QP and operational capacity. To ensure supply chain continuity in EU clinical trials, sponsors simply cannot afford to wait for negotiations to end before taking action.
As the clock ticks toward 2019, the only way to mitigate the impact of this disruption is to begin planning now.
Important criteria for a partner to support your current and future needs
Perhaps the most important question you will need to answer is whether your current CMO can support you going forward—which will depend on both trials underway and your future plans. Does your current vendor have facilities in the EU (outside the UK), and importantly, the capacity to support all your requirements?
You may determine the need to bring on additional sources. In this case, the following checklist can help you begin the evaluation process. A best-in-class vendor will offer the following.
- GMP facilities located in the EU: A “Brexit-ready” global depot network with robust and proven supply management distribution capabilities for clinical trials and EU QP resource.
- Comprehensive, integrated services, encompassing:
- Clinical trial supply—project management, inventory forecasting and planning, packaging, labeling and distribution
- Randomization and trial supply management—blinded clinical trial management, with services to design and manage real-time recruitment, randomization, treatment allocation, closing, dispensing and site supply management
- Ancillaries and devices management—centralized management to reduce shipments and thereby, logistics costs
- Lab logistics services—access to a broad spectrum of market-leading analysis and assays, with data entered directly into a single system in an integrated process
- Global trade compliance—an organization responsible for pre-screening of documentation to prevent compliance issues that could result in reputational or financial damage, with a team that stays apprised of ongoing changes in tax and trade tariffs
- Advanced technology: an integrated platform for maintaining full visibility into supplies, logistics and randomization, including state-of-the-art functionality such as active tracking for temperature-controlled substances
In a period of significant uncertainty within the EU and global markets, it is critical that as an industry, we plan ahead, focusing our decision-making on what we do know and keeping a watchful eye on what we do not. One thing certain is that change is coming, and taking early action to manage this change through robust supply chain continuity planning is essential to post-Brexit success.