Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
Ireland Asks Companies to Proactively Discuss Possible Effects of Brexit to Avoid Disruptions
The Irish Health Products Regulatory Authority (HPRA) has asked companies to contact it with details of disruptions that may occur in the event of a no-deal Brexit. HPRA wants to learn of Brexit-related product withdrawals and clinical supply problems ahead of time so it can look into mitigating actions.
Irish officials made the request in the latest HPRA newsletter, around one-third of which is focused on Brexit. The Brexit-related topics covered in the newsletter include the potential for companies to withdraw products from the Irish market as a result of the United Kingdom’s departure from the European Union.
HPRA wants companies in this situation to contact it, as it is open “to discussing regulatory solutions that may avoid the need to withdraw a marketing authorization or registration.” The HPRA offer is open to manufacturers of human and veterinary medicines.
Companies can contact HPRA via their regular touchpoint with the agency. The HPRA contact will then “coordinate discussions in confidence,” enabling companies to share information about possible withdrawals without committing to a particular course of action.
HPRA has extended the offer to the industry to try to prevent product shortages arising as a result of Brexit. The agency published the newsletter before the European Medicines Agency (EMA) released guidance confirming that companies can continue to sell multi-country medicine packs covering the UK market after Brexit, thereby eliminating a possible cause of withdrawals and shortages in Ireland.
If the withdrawal of a product is unavoidable, HPRA wants companies to follow its guidance on the withdrawal of human medicines for commercial reasons or the comparable document on veterinary treatments.
Elsewhere in the newsletter, HPRA addresses the potential for Brexit to disrupt the supply chains that support clinical trials. HPRA is encouraging companies that may face this situation to contact it, too. As with withdrawals, HPRA thinks early engagement with clinical trial sponsors will give it time to “fully explore all available options” and thereby cut the risk of disruption of shipments to Irish study centers.
The newsletter was one of several Brexit-related notices published by HPRA this week. In addition to alerting people to the EMA guidance on multi-country packs, HPRA released a notice about changes to the VPA marketing authorization numbers of veterinary medicines as a result of companies transferring product registrations from the UK to one of the remaining 27 EU member states.
As “the volume of such transfers has increased in recent months as a consequence of Brexit” there will be products on the market that feature the same marketing authorization holder but different VPA numbers. HPRA wants people who handle veterinary medicines to be aware of the discrepancy to avoid confusion.
, VPA Notice
EMA Seeks Feedback on Revised Antimicrobial Categorization Based on Resistance Risk
EMA has proposed a new way of categorizing veterinary antimicrobials based on the risk they pose to human health. The system considers the importance of each antimicrobial class to humans and the likelihood of drug resistance transferring from animals to determine which category is appropriate.
Europe adopted a three-tier system in 2014 that classed antimicrobials as either low-risk, higher risk or not approved for use in animals. The process of moving away from that model began in 2017 when the European Commission asked EMA to reconsider the system in light of reflection papers on aminoglycosides and aminopenicillins in animals and other experience gained since 2014.
In reviewing the system, EMA’s Antimicrobial Advice ad hoc Expert Group (AMEG) has placed more emphasis on the availability of alternative veterinary antimicrobials. AMEG has also added a fourth category and included classes of antimicrobials it left out of the 2014 system.
The four categories are referred to by the words avoid, restrict, caution and prudence. The avoid category features antimicrobials not authorized for veterinary use in the EU. Restrict corresponds to the older higher risk category and as such includes quinolones and other antimicrobials that should only be used in animals when no alternatives are available. Prudence is the old lower risk category.
Caution, also known as Category C, is the new addition to the risk-ranking system. This intermediate category features antimicrobials for which there are alternatives in human medicine but few different options in veterinary medicine. AMEG is also proposing to put antimicrobials that may select for resistance to a substance in the avoid category in this group.
EMA released the proposed new categories for consultation this week and is accepting feedback on the draft until the end of April. Once finalized, the new system of categorization will support the creation of guidelines on the use of antimicrobials in veterinary medicine.
, Draft Categorization
France Creates Procedure for Handling Whistleblower Reports
The French medicines regulator has created a procedure for whistleblowers who have information of serious legal or regulatory violations. Officials have created a dedicated email for the reporting of the information and promised to quickly review and respond to all submissions.
Two years ago, France passed a law intended to support efforts to tackle corruption that featured a section on the protection of whistleblowers. Working within that legal framework, France’s Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) has set up a dedicated email address for whistleblowers and created a process for handling information sent to it.
When ANSM receives information, it will quickly review the materials and get back to the person who submitted it. ANSM may then follow up on a report by conducting an inspection, analyzing products in its laboratories, verifying the authenticity of files or otherwise advancing the investigation.
Throughout the process, ANSM will take steps to ensure the confidentiality of the source of the information, particularly from their employer. French law permits punishments of up to two years in prison and fines of €30,000 ($34,000) for people who disclose confidential information shared by whistleblowers.
EMA Reviews Bleeding Risk of Anticoagulants From Bayer, Boehringer and B-MS
EMA is reviewing the results of an observational study into the risk of bleeding associated with direct oral anticoagulants (DAOCs) sold by Bayer, Boehringer Ingelheim and Bristol-Myers Squibb. The study linked Bristol-Myers’ Eliquis to a lower risk of bleeding than the other direct oral anticoagulants.
European regulators identified the need for more data on the real-world use of anticoagulants in 2015. That led EMA to request a postapproval trial designed to compare the risk of major bleeding associated DAOCs and other oral anticoagulants (AOCs) in people with non-valvular atrial fibrillation (NVAF).
The researchers have now presented the results of their analysis of 251,719 patients in four European countries. In all bar one country, Bayer’s Xarelto and Boehringer’s Pradaxa were associated with statistically significant increases in the risk of gastrointestinal bleeding compared to AOCs. Eliquis, in contrast, was linked to statistically significant reductions in bleeding risk in two of the four countries.
Other parts of the study looked at uptake of the DOACs in NVAF and the extent to which physicians are adhering to recommendations about their use. The study found use of DOACs, particularly Eliquis, rose during the examined period but that adherence to usage recommendations is patchy.
EMA is still reviewing the findings but has already said it may act on what it has learned. The review will look at whether regulatory changes to minimize the risk of bleeding are required.
. Study Abstract