The main challenges for companies ahead of Brexit surround the uncertainty of the outcome of negotiations and the complexity and cost of moving operations and licenses, said Parastoo Karoon, PhD, principal consultant, Parexel Consulting.
“Such a move is not only a regulatory action, it also involves financial, logistic, staff relocation, tax brackets and more,” she told Outsourcing-Pharma.com. “This is because any pre-emptive large scale, costly move that may prove unnecessary at a later stage will have to be justified to their boards of directors and shareholders.”
Brexit marks the United Kingdom’s (UK) departure from the European Union (EU). The move is expected to occur March 29, 2019, providing there is no extension of negotiations.
Ahead of this date, Karoon said most large companies have formed a Brexit Task Force and are participating in EMA workshops and following EMA guidelines closely. “Medium to small size companies without internal task forces follow Brexit related events closely,” she added.
Most noticeably, Karoon told us there seems to be a trend of companies avoiding MHRA/UK for new product applications, though no statistics are available.
The MHRA (Medicines and Healthcare products Regulatory Agency) regulates medicines, medical devices, and blood components for transfusion in the UK.
Ensuring standards are maintained
The industry needs to plan to transfer the Reference Member State (RMS) to another EU National Competent Authority in cases where the MHRA acts as the Reference Member State, explained Bridget Heelan, vice president-technical, Parexel Consulting.
“If planning a study with a reference product (e.g. a bioequivalence study) then the reference product will need to be an EU marketed product,” Heelan told us.
Additionally, Karoon said companies should be closely following EMA, Coordination Group for Mutual Recognition and Decentralized Procedures-Human (CMDh) and MHRA guidelines in addition to following the EU Commission.
“Also, the companies should try to finalize any ongoing variations and avoid submitting new ones that the time table may clash with official Brexit date,” added Karoon. “In case of doubt then liaison with the relevant regulatory authorities is recommended.”
Outcomes of the negotiations and the future of UK relationship with the EU will become clearer by October 2018, Karoon explained.
The clinical trials supply chain
The EU requires the “gateway” for a Qualified Person (QP) release and distribution of investigational product to be sited in a member country, explained Tony Street, head of global portfolio leadership and account development, clinical trial supplies and logistics, Parexel.
“If a clinical trial sponsor or their contract manufacturing/logistics provider is using the UK as that gateway, then that currently approved supply route is at risk,” he said.
The requirement applies to all global pharmaceutical companies conducting studies with sites in EU countries. Guidance has been provided to give marketing authorization holders of centrally authorized medicinal products some initial direction, said Street, though many details remain unresolved.
According to the guidelines issued jointly by the EMA and the European Commission, the UK will become a “third country” beginning March 30, 2019. Though the guidance is for commercial drug releases, Street said it is a “strong indicator” of what will be applied to investigational medical products (IMPs).
“The implication of the guidance is that if a clinical trial sponsor’s QP release and clinical trial distribution to sites in EU countries is currently located in the UK, they are likely to have to relocate it to a remaining EU member country,” he explained.
“Although there are uncertainties, we do know enough to assess potential risks to the clinical trial supply chain and take actions to mitigate them,” said Street.
“Parexel’s advice is don’t wait,” he added, “the clock is counting down fast towards March 2019, and the risks are compounded by many QPs being located in UK based facilities today, which could lead to competition for those scarce resources.”
Clinical trial supply 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? If so, Street explained companies will need to transfer release from the current UK-based site to a location in the European Economic Area (EEA) and submit an amendment to the clinical trial authorization.
If the UK is the current location of the QP, Street said the person will need to relocate to the EU, or the company will need to appoint a new QP named on an appropriate license 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,” said Street. However, he explained companies should expect a potential increase in tax and duty expense, in addition to increased costs for a UK-specific release, if required.
The post-Brexit GMP import process into the UK remains to be defined, Street added.