Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
Ireland’s HPRA Floats Fee Increases as Brexit Creates Challenges
Ireland’s Health Products Regulatory Authority (HPRA) is planning to introduce new fees and increase existing charges. HPRA framed the fee increases in light of the increasingly challenging environment in which it operates, pointing to Brexit, new medical device rules and an increase in the complexity of the regulatory model and the products it oversees.
If HPRA’s proposals go ahead, the agency will apply a general 3% increase to all human medicine, compliance, blood, tissue and organs and medical device fees in 2020. HPRA is also planning to create some new fees and increase the payments for some services by more than 3%.
The new fees include the introduction of supplemental charges for mutual recognition procedures that are applied for within six months of the national procedure ending. HPRA wants to create the new fee, which could be as much as €15,450 ($17,000), to bring its rates in line with decentralized outgoing fees for new products.
Many of the fees HPRA wants to increase by more than 3% relate to medical devices. The agency is planning to charge companies €600 to appeal a determination decision. In the event of arbitration between a medical device company and notified body over determination, HPRA will charge €5,000. HPRA currently lacks an arbitration fee.
HPRA also plans to increase the fee for devices using starting materials for which a transmissible spongiform encephalopathy certificate of suitability has been submitted by 150%, arguing that the review process has become more complex since it last set the rate.
The agency cited rising complexity of the global supply chain and the resulting oversight challenges to justify a 20% increase in the manufacturing annual maintenance fees. HPRA also addressed the broader trend for greater complexity in its comments about the operating environment in 2019.
“The regulatory model is becoming more complex, there are more complex medicines and the pharmacovigilance legislation has led to an increase in the number of referrals and regulatory action arising from the outcome of these referrals. Public scrutiny and the role of the regulator in relation to medicines such as the HPV vaccine has increased, and compliance activity, particularly outside of Ireland, is also increasing,” HPRA wrote.
HPRA is contending with the changes at a time when, in its words, “Brexit has brought considerable uncertainty to the regulatory framework.” Brexit accounted for most of the increase in regulatory activity at HPRA in 2019. With the trends identified in the report likely to continue into 2020, HPRA plans to increase its headcount.
A separate consultation document on proposed veterinary medicine fees covered similar ground, while also zeroing in on the effect of incoming animal medicine rules. HPRA said the legislation will “significantly” affect its veterinary medicinal product regulatory program and “increase requirements for compliance monitoring, changes to the data requirements, transparency and further controls.”
, Veterinary Fees
Scottish Government Sketches Out Regulatory Fears About No-Deal Brexit
The Scottish government has outlined the potential impacts of a no-deal Brexit and the actions it is taking to mitigate them. Scottish authorities think a civil contingencies response to the change in the regulatory framework will be needed on day one of a no-deal Brexit.
In the 30-page overview of its no-deal Brexit preparations, the Scottish government outlines some of the regulatory and trade concerns that the industry has discussed since the United Kingdom voted to leave the European Union.
The Scottish government has some devolved powers, but the authority to take many of the actions it thinks are needed rests with the UK government. As such, the overview of the Scottish government’s preparations for no deal is a mix of actions it is taking and steps it wants the UK government to take.
Many of the powers required to mitigate the regulatory implications of a no-deal Brexit rest with the UK government. The Scottish government wants its UK equivalent to “ensure that the regulatory and licensing arrangements are in place to ensure continued access to medicines, medical supplies and medical radioisotopes” and to share data on the continuity of supply.
The Scottish government has more power to mitigate some of the logistical problems that may arise from the change in rules on cross-border trade. Notably, the Scottish government has plans to use ports in the country to bypass the potential bottleneck at the Dover-Calais crossing between England and France.
Those plans reflect a belief that the supply of medicines is “likely” to be disrupted. The UK government is more optimistic, with one of its representatives telling Parliament this week that its efforts “should ensure the uninterrupted supply of medicines.”
, UK Statement
PRAC Recommends Limiting Use of High-Strength Estradiol Creams
The Pharmacovigilance Risk Assessment Committee (PRAC) has recommended capping the duration of use for high-strength estradiol creams at four weeks. PRAC proposed the restriction to minimize the risk of side effects including blood clots, stroke and breast cancer.
Estradiol creams are applied topically to treat symptoms of vaginal atrophy in women who have been through menopause. However, data reviewed by the European Medicines Agency’s (EMA) PRAC link use of the creams to blood estradiol above normal postmenopausal levels. That finding led PRAC to conclude the creams could have similar side effects to hormone replacement therapy (HRT).
Given the severity of the side effects linked to HRT, and in the absence of long-term safety data, PRAC is proposing to limit use of high-strength estradiol creams to four weeks. PRAC is also advising physicians not to prescribe high-strength estradiol creams with other HRT medicines.
The European Commission triggered the review of the creams in the wake of the ruling by the Court of Justice that partially annulled the findings of a review PRAC conducted in 2014. The annulment was driven by procedural matters.
MHRA Asks Manufacturers to Quarantine Ranitidine Medicines
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has asked manufacturers to quarantine all ranitidine products that may be contaminated by N-nitrosodimethylamine (NDMA).
GlaxoSmithKline is recalling all unexpired stock of four types of its ranitidine medicine Zantac from the UK in response to the contamination concerns. In parallel, MHRA is investigating whether other ranitidine medicines may be contaminated by the carcinogen NDMA. MHRA wants manufacturers to quarantine products at risk of contamination while its investigation is ongoing.
The quarantined products could ultimately be recalled depending on the outcome of the MHRA investigation. MHRA has asked companies to support the process by testing potentially affected batches as part of assessments of the risks they pose.
MHRA issued its notice days after Ireland’s HPRA provided its own update. The update disclosed the expansion of the Irish Zantac recall to cover all in-date batches of 150mg film-coated tablets. HPRA asked GSK to exclude intravenous and syrup formulations of Zantac from the recall as it has seen no evidence NDMA has harmed patients and there is a lack of authorized alternatives for the products. The UK recall included injectable and syrup versions of Zantac.
, HPRA Notice
has revised its guidance on post-orphan medicinal product designation procedures. The changes to the document relate to the submission of the report on the maintenance of the orphan designation after the marketing authorization is validated. EMA Guidance