Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
UK Plans to Add 5,000 Pallets of Refrigerated Storage to Mitigate Hard Brexit
The United Kingdom government expects to expand cold chain storage capacity ahead of a potential no-deal Brexit with refrigerated space for 5,000 pallets. Government officials also expect to add 53,000 pallets of ambient storage and 850 pallets of controlled drug storage.
Efforts to add storage capacity began last year after the government learned the medicine industry had insufficient space to comply with a request to stockpile enough products to last six weeks. Faced with the prospect of border checks stopping the flow of medicines into the UK, the government put out an appeal for storage to enable companies to stockpile more medicines ahead of Brexit.
Writing in response to questions from an opposition politician, Stephen Hammond, minister of state at the Department of Health and Social Care, sketched out the progress of efforts to increase the UK’s storage capacity.
Hammond expects the additional ambient, refrigerated and controlled drug storage to come online by the start of February and remain in place for 12 to 18 months. The money offered by the government, which could run to “low tens of millions of pounds,” is being made available on the condition that the capacity is ready by the start of February. The additional refrigerated capacity will cost the government around £1 million ($1.3 million).
As it stands, it is unclear whether the UK will need the additional capacity. The government is seeking the storage to facilitate the creation of stockpiles capable of mitigating disruption to trade that could occur in the event of a no-deal Brexit.
That possibility remains alive as a result of Parliament's rejection of the withdrawal terms UK Prime Minister Theresa May agreed upon with the European Union. May now has until Monday to present an alternative exit agreement to Parliament, which is scheduled to vote on this plan B before the end of the month.
If Parliament accepts a deal or the UK delays its departure from the EU, the extra storage capacity will be surplus to requirements. However, the government “will be liable for some capital costs already incurred by the contractors,” Hammond said.
EMA Floats Expansion of Biomarker Section of Oncology Clinical Trial Guidance
The European Medicines Agency (EMA) is planning to update guidance on the clinical development of cancer drugs. EMA only brought the current version into force in April, but thinks further changes are needed to bring the guidance in line with recent changes in the use of biomarkers in oncology and hematology.
EMA’s Committee for Medicinal Products for Human Use adopted the current, fifth revision of the guideline on the evaluation of anticancer medicinal products in September 2017 and brought it into effect the following April. Despite that relatively recent revision, the pace of change in cancer drug development has persuaded EMA that further changes are already needed, leading the agency to publish a draft concept paper setting out its plans.
“Since the adoption of the guideline, the use of biomarkers in oncology and hematology has evolved and progressed considerably.” EMA wrote. “This has resulted in novel development strategies as well as new definitions of therapeutic indications based on biomarkers. The current guidance does not adequately address these new aspects.”
The divergence between the guidance and clinical development practices centers on the shift in how diseases are defined. Whereas cancer indications were once defined by anatomy or histology, they are now increasingly divided up on the basis of biomarker status. The shift recognizes that diseases once seen as homogenous, such as lung cancer, are in fact made up of many molecularly defined subgroups. Some subgroups can be vulnerable to the same drugs even if they affect different organs.
A landmark event in the shift occurred in May 2017, one month after EMA’s Oncology Working Party adopted the current version of the text, when the United States Food and Drug Administration approved Merck’s Keytruda for use in any solid tumor with a certain genetic feature. The approval was the first time a drug had been cleared based on a biomarker, not a tumor location.
With other drugs now in development against biomarkers shared by multiple types of tumors, EMA wants to update its guidance to reflect the current landscape. The concept paper sketches out EMA’s reasoning ahead of an anticipated rewrite of the guidance that would expand the biomarker section. EMA foresees the expanded section addressing the evolving scientific concepts, the role biomarkers play in drug development and the main questions that sponsors need to address.
EMA also plans to use the update process to discuss new study designs, such as basket and umbrella trials, that are not addressed in the current document. These biomarker-based designs enable drug developers to test different candidates on different mutations in a single form of cancer, or assess the effect of one or more drugs on mutations in a range oncology indications.
Umbrella and basket trials have grown in popularity in recent years as sponsors have tried to identify and treat biomarker-based subpopulations. However, as EMA thinks “regulatory experience is limited in this field” it plans to limit its revision of the guidance to the “main aspects and principles.”
EMA is accepting feedback on the draft concept paper until 14 April. The agency is aiming to have a first draft of the new guideline ready for consultation by the second quarter of the year.
Dutch Regulator Braces for Brexit by Identifying Critical Drugs Linked to UK
The Dutch Medicines Evaluation Board (MEB) has outlined the work it is doing to prepare for a hard Brexit. MEB’s latest initiative is focused on identifying critical medicines with supply chains that are vulnerable to disruption in the event the UK leaves the EU without a deal in March.
With the UK shipping 45 million packs of medicines to the rest of the EU each month, the supplies of many products could be disrupted if cross-border trade breaks down for a time after Brexit. In some cases, European countries will have access to alternative drugs or will otherwise be able to mitigate the impact of the supply disruption, but there may be products for which this is impossible.
To ensure it is forewarned about these dangers, MEB is identifying drugs with supply chains involving the UK that are used by patients in the Netherlands. MEB is particularly interested in critical drugs, such as life-saving medicines for which no alternatives are available.
MEB’s notice comes four months after it published a statement about its preparations for a no-deal Brexit. Back then, MEB highlighted how it was using temporary financial support from the Ministry of Health, Welfare and Sport to add to its internal capacity in anticipation of a Brexit-related increase in its workload.
’s Committee for Medicinal Products for Veterinary Use
has adopted guidelines on DNA-reactive impurities and inactivated vaccines. The impurities guideline, which comes into force next year, covers the steps manufacturers of veterinary medicines should take to assess and control the risks posed by mutagenic substances. EMA’s inactivated vaccine guideline, which comes into force in July, addresses the data requirements for products against diseases including avian flu. Impurity Guideline
, Vaccine Guideline