Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
MHRA Extends EpiPen Expiry Dates to Mitigate Supply Shortages
MHRA has allowed Mylan to extend the expiry dates on certain lots of EpiPen to mitigate supply constraints. The organizations think delaying the expiry of nine lots of the adrenaline auto‐injectors by four months will help ensure patients can access the products while Mylan stabilizes supply.
The extensions push the expiry dates for the lots of 0.3mg auto-injectors out to between November and March. If all goes to plan, Mylan will have recovered from its production interruption by the time of the revised expiry dates, enabling it to bring new lots to market to replace the out-of-date devices. Until then, supply will be constrained in the UK and elsewhere.
Details of the expiry date extensions emerged the day before MHRA published a supply disruption alert about EpiPen. The alert stated the EpiPen Junior product is out of stock. MHRA expects it and the standard EpiPen to be subject to limited availability for the rest of the year.
To mitigate the effect of the disruption, MHRA is advising physicians to limit prescriptions of the products “to those who truly need them.” Some patients may need to switch from their preferred 300mcg and 150mcg EpiPen devices for the duration of the supply disruption.
, Supply Alert
Ireland Revises Batch-Specific Request Rules to Prevent Shortages
Ireland’s Health Products Regulatory Authority (HPRA) has revised its guidance on batch-specific requests (BSR) for human medicines. BSRs enable companies to ensure the continued availability of their medicines when a product deviates from the registered marketing authorization.
That core focus of the BSR program is consistent across the second and third versions of the HPRA’s guide. However, the regulator has made significant changes that affect when marketing authorization holders (MAHs) can apply for BSRs and what will happen if their request is granted. The revisions to the guide follow broader changes to the management of drug shortages in Ireland.
In a reflection of its recent prioritization of drug shortages, HPRA has amended the guide to permit MAHs to class BSRs as urgent. HPRA wants MAHs to categorize filings as urgent when no alternative medicines are on the market in Ireland and the product is classed as “critical” under the criteria set out by the European Medicines Agency (EMA). Urgent filings will benefit from a “rapid turnaround time” at HPRA. The agency aims to start assessing non-urgent BSRs within five working days.
Elsewhere in the guide, HPRA states the use of BSRs is limited to “critical” medicines — a term absent from the earlier HPRA document — with one exception. In some instances, HPRA will accept BSRs for non-critical, nationally authorized medicines “in order to correct a quality defect or to bring a batch into compliance with its registered MA dossier.”
Other changes to the guide further clarify when MAHs can submit BSRs. The guide now states MAHs can use the BSR procedure to extend the implementation of changes to labels and leaflets that are agreed during renewal. The new text expands on an existing statement that companies can use the BSR procedure when an extension to the implementation time for approved variations is needed. The mechanisms give MAHs a way to obtain more time to implement approved changes.
In this way, BSRs can help to ensure the continued availability of medicines. When used for this purpose, BSRs typically cover enough packs or batches to supply the market for three months. That restriction was set in the earlier guides and carried over into the latest version. HPRA has added some flexibility to the time limit, though. BSRs used to correct quality defects now last indefinitely.
The revised guide also provides more details about what HPRA expects of manufacturers that ship products under BSRs. If HPRA agrees to allow a MAH to perform the “rubber-banding” of leaflets or letters to the outer packing of a product, the attachment of this paperwork does not need to be carried out by an authorized producer under good manufacturing practices. However, HPRA does expect the responsible person at an authorized wholesaler to oversee the process.
Bayer Vows to Appeal UK Court Ruling on use of Avastin in AMD
Bayer has vowed to appeal a United Kingdom court ruling that permitted the use of Roche’s Avastin in wet age-related macular degeneration (AMD). The appeal will seek to overturn a decision Bayer thinks was based on conclusions that are “wrong in a number of key respects.”
Last month, Justice Philippa Whipple ruled against Bayer and Novartis in a case in the High Court in London. Whipple concluded that the National Health Service (NHS) can use Roche’s Avastin to treat wet AMD, despite it not being approved for use in the indication. In doing so, Whipple ruled bodies other than EMA can determine the safety, efficacy and quality of medicines used in the UK.
A week after receiving the ruling, Bayer committed to try and overturn it in the Court of Appeal. The appeal will focus on two issues Bayer thinks Whipple got wrong in her ruling. Bayer will argue that the policy of Avastin use adopted by parts of the NHS “undermines the comprehensive licensing regime for medicines across the [European Union] ... and the role of the EMA and the [Medicines and Healthcare products Regulatory Agency (MHRA)].”
Whipple called the argument that EMA has exclusive competence over safety, efficacy and quality “an absurd proposition” that would “give unbounded power to the pharmaceutical companies to decide which medicines to make available for which purposes.” Bayer sees things differently and plans to find out whether the appeals court will favor its interpretation of the law.
Nordic Countries Postpone Schedule for Joint Procurement Plan
Denmark, Iceland and Norway have delayed the publication of tenders for their joint procurement initiative. The Nordic countries are framing their initiative as a way to improve the security of drug supply while lowering prices.
In a presentation last week, Denmark, Norway and Iceland said they would share tender documents on 3 October and give the industry until 12 October to comment. However, the people behind the proposal subsequently received feedback that persuaded them to delay the plan. A revised schedule that will give suppliers more time to comment is in development.
The rethink defers the signing of deals the countries think will solve some of the problems they face. The initiative is focused on off-patent products that are only provided by a few suppliers, at most. The monopoly power and supply risks this situation creates is a problem in many markets, but the Nordic countries think their small size puts them at particular risk. By teaming up, the countries hope to create a larger market that is more attractive to suppliers.
In their presentation, the countries identified 11 products that are potentially at risk of disruptions to supply. The list includes the antibiotics ampicillin, benzylpenicillin and piperacillin, methotrexate and intravenous paracetamol.
The focus on off-patent drugs sets the Nordic initiative apart from other European joint procurement programs. BeNeLuxA, the growing procurement group that started in Belgium and the Netherlands, is more focused on scanning the horizon for new medicines and cooperating on health technology assessments.
The Danish Medicines Agency
(DKMA) has received a regulatory delegation from China
. DKMA Notice