Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
 
Ireland Details Efforts to Mitigate Impact of No-Deal Brexit on Device Supply
 
Ireland’s Health Products Regulatory Authority (HPRA) has shared details of its work to mitigate the risk that a no-deal Brexit will disrupt the supply of medical devices. HPRA wants companies to consider their stocking levels and make arrangements to ensure they can replenish their supplies in the run up to 31 October and beyond.
 
In the notice, HPRA highlighted the need for medical device companies to transfer CE mark certificates from notified bodies based in the United Kingdom to groups located in one of the 27 member states that will still be in the European Union after Brexit. HPRA also stated that medical device companies need to relocate European Authorized Representatives from the UK to another member state.
 
HPRA has made these points before, most recently in a newsletter published in June, and other EU regulators, including the European Medicines Agency (EMA), have covered similar ground. However, with six weeks to go until the UK is due to leave the EU, and with little sign Prime Minister Boris Johnson can resolve the impasse, HPRA still thinks it is necessary to state the actions the industry needs to take.
 
The notice is the latest public indication of the work HPRA is doing to prepare Ireland for a no-deal Brexit. Earlier this month, HPRA issued similar notices about what it is doing — and what it wants the industry to do — to cut the risk that a no-deal Brexit will disrupt the supply of human and veterinary medicines.
 
All three notices detailed the same supply chain recommendations. HPRA wants companies that sell drugs and medical devices to “take the necessary steps to ensure sufficient stock levels,” including by “ensuring arrangements are in place to allow for timely replenishment of such stocks.” That could mean adopting custom requirements and allowing for potential transportation delays.
 
Ireland is the second biggest net exporter of medical devices in the EU, after Germany, potentially making it less vulnerable to transportation disruptions than some other countries. However, the Irish supply chain is entangled with the UK and it still imports significant quantities of medical devices. 
 
HPRA Notice
 
FInland Pulls Ranitidine Medicines From Pharmacies Over Carcinogen Concerns
 
The Finnish Medicines Agency (Fimea) has withdrawn ranitidine drugs including GlaxoSmithKline’s Zantac from pharmacies over quality concerns. Fimea’s action follows the initiation of investigations in the United States and EU into the presence of carcinogenic contaminants in the medicines.
 
Authorities on both sides of the Atlantic began looking into whether products that use ranitidine, a heartburn medication, may contain N-nitrosodimethylamine (NDMA) last week. NDMA is one of the carcinogenic contaminants that led to regulatory actions against the sartan class of blood pressure drugs.
 
Fimea followed up on the initiation of the regulatory investigations by withdrawing six medicines from pharmacy distribution. However, Fimea wants patients currently taking the withdrawn drugs to continue doing so until they receive a replacement. That position reflects the belief that NDMA is unlikely to be harmful to humans at very low concentrations.
 
The Finnish agency is now investigating the contamination risk in collaboration with its counterparts in other EU countries.
 
Fimea Notice (Finnish)
 
MHRA, Gates Foundation Team up to Research Medicine Use During Pregnancy
 
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has joined forces with the Bill & Melinda Gates Foundation for a research project. MHRA will work with the nonprofit to assess the efficacy and safety of medicines during pregnancy.
 
Using a $360,000, two-year grant from the Gates Foundation, MHRA will work to predict the level of dosing adjustments needed to ensure medicines are safe and effective, for the mother and fetus, at different trimesters of pregnancy. MHRA researchers will use physiologically based pharmacokinetic models and simulations and other tools to develop recommended medicine dosages for women.
 
MHRA plans to train healthcare professionals to use the models and create a web portal to host its research into interactions between the changes that occur during pregnancy and drug exposure. Research groups will use the portal to upload and share their modelling.
 
“This work provides a valuable launch pad for new developments into, and improved understanding of how pregnancy affects medicine levels. That’s why we are encouraging healthcare professionals, research groups and those looking to supply medicines during pregnancy, to make full use of the prediction models, data and resources we will provide,” June Raine, MHRA’s director of vigilance and risk management of medicines, said.
 
Press Release
 
Spain Creates Process for Reporting Veterinary Medicine Supply Problems
 
The Spanish Agency of Medicines and Medical Devices (AEMPS) has created a procedure to enable marketing authorization holders (MAHs) and other groups to report shortages of animal medicines.
 
MAHs are required under Spanish law to report abnormal restrictions to the supply of their products. Healthcare professionals and other individuals, such as farmers, do not have the same obligation but are well placed to detect and report supply problems. AEMPS wants to help each group report supply disruptions.
 
To do so, AEMPS has created a reporting option within its RAEVET online portal for use by MAHs. The option enables MAHs to attach documents disclosing veterinary medicine shortages. After AEMPS accepts a shortage report, details of the supply disruption will be included on a list on the CIMAVet website.
 
Healthcare professionals and farmers lack access to RAEVET. As such, AEMPS is encouraging these individuals to submit reports via another portal maintained by another Spanish government agency.
 
AEMPS Notice (Spanish)
 
CVMP Recommends Approval of 2 Veterinary Vaccines
 
EMA’s Committee for Medicinal Products for Veterinary Use (CVMP) has recommended approval of two new vaccines. The vaccines are designed to protect chickens and rabbits from certain viruses.
 
The chicken vaccine, which was submitted by Laboratorios Hipra, protects one-day-old broiler chicks and embryonated broiler chicken eggs from the effects of a virulent avian viral infection. CVMP recommended authorization of the vaccine by a majority positive opinion.
 
The committee recommended the rabbit vaccine, Intervet International’s Nobivac Myxo RHD Plus, by a consensus positive opinion. Intervet developed the vaccine to reduce deaths by myxomatosis and two viruses that cause hemorrhagic disease. The rabbit vaccine is classed as a minor use, minor species product, the veterinary equivalent of an orphan medicine.
 
CVMP Notice
 
Other News:
 
The Dutch Medicines Evaluation Board (MEB) has given companies until 1 November to submit withdrawal requests for marketing authorizations. Companies that submit requests after that date will need to pay the annual fee for 2020. If the application is filed on time but the product remains on the market in 2020, MEB will charge the fee but issue a credit note when the drug is withdrawn. MEB Notice
 
Dr. Reddy's Laboratories has begun recalling a batch of aripiprazole from the UK in response to the discovery of small particles of the active ingredient. The small particles could affect the efficacy of the product. Dr Reddy’s took the action after receiving a complaint related to the discovery of a precipitate in a bottle of aripiprazole. MHRA Notice
 
The French National Agency for Medicines and Health Products Safety (ANSM) has published its annual report for 2018. The report reveals a sharp increase in reports of drug shortages, which rose from 538 in 2017 to 871 last year. ANSM reported little year-on-year change in the other metrics tracked in its annual reports. Annual Report