Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
UK Confirms US Sites Can Batch Test Drugs in Event of a No-Deal Brexit
The United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) has confirmed it will accept results from batch testing performed in the United States in the event of a no-deal Brexit.
MHRA published the original list of countries authorized to perform batch testing weeks before the UK was due to leave the European Union in March. At that time, MHRA said no batch testing done in the US would be accepted after Brexit because such work was outside the scope of the mutual recognition agreement between America and EU until the assessment of member state equivalence was finished.
The March guidance left the door open for a change in position, noting that the situation “remains under review.” Now, an update to the guidance has added the US to the list of locations authorized to perform batch testing.
Under the new guidance, MHRA will allow most medicines that undergo batch testing in the US into the UK if there is a no-deal Brexit. The exceptions are vaccines, advanced therapy medicinal products and medicinal products derived from human blood or plasma.
The update was part of a wave of revisions to MHRA’s suite of no-deal Brexit guidance documents. In many cases, the changes are limited to little more than what the agency calls the removal of “some outdated background information.” In keeping with other recent changes to no-deal guidance, the most significant revision to these documents is the removal of a statement about the UK prioritizing leaving the EU with a deal.
NICE Gives Downbeat Assessment of Value of Cannabis-Based Medicines
The UK National Institute for Health and Care Excellence (NICE) has recommended against the use of cannabis-based medicines in multiple contexts. NICE’s preliminary position is that physicians should consider synthetic cannabinoid nabilone as an add-on treatment for chemotherapy-induced nausea and vomiting (CINV) but otherwise avoid the use of cannabis-based medicines.
In assessing the value of cannabis-based medicines, NICE looked at the data on the use of multiple products in the treatment of intractable nausea and vomiting, chronic pain, spasticity and severe treatment-resistant epilepsy.
NICE recommended against the use of nabilone, dronabinol and THC, either alone or in combination with CBD, in the management of chronic pain. That position reflects NICE’s belief that the effect of the medicines on pain is modest and the forecast is for high and ongoing costs associated with their use in the indication. NICE thinks CBD can be offered in clinical trials, given the current lack of data.
The cost watchdog reached a similar conclusion about the use of GW Pharmaceuticals’ Sativex in the treatment of spasticity in people with multiple sclerosis. NICE identified benefits to the use of the THC:CBD spray but concluded the cost per pack needs to come down from £375 ($453) to £188 for its use to meet the quality of life gain threshold.
NICE opted against making a recommendation for severe treatment-resistant epilepsy in light of the lack of good quality evidence in the indication.
That left CINV as the only indication to get a positive recommendation. Even that recommendation was equivocal. NICE found evidence linking nabilone to complete and partial reductions in CINV, but the studies that generated those results were “old, of low quality and used outdated antiemetic regimens that do not reflect current practice,” the organization said.
Given those shortcomings and the lack of long-term adverse event data, NICE limited its nabilone recommendation to adults with intractable CINV that persists despite the use of optimized conventional antiemetics.
NICE is accepting feedback on the draft recommendations until 5 September.
Germany Permits Clinical Trial Filings via Common European Submission Portal
Germany’s Federal Institute for Drugs and Medical Devices (BfArM) has begun accepting applications to run clinical trials via the Common European Submission Portal (CESP). Use of the electronic portal will provide an alternative to the submission of paper applications and physical media such as DVDs.
CESP has provided companies with a secure electronic way to communicate with national regulatory agencies for years, but its use in the submission of clinical trial requests remains patchy. The CESP frequently asked questions page states “a number of agencies” accept clinical trial filings through the system. BfArM is now one of those agencies.
Applicants that use the portal to make clinical trial requests to BfArM will not need to submit physical media. However, the paper-based route, supported by information sent via physical media, remains open to companies that do not want to use the portal.
Romania Mandates Five-Fold Increase in Marketing Authorization Fee
Romania has increased the fee applicants must pay when they submit a marketing authorization filing by five times. The new fee is €5,000 ($5,589), up from €1,000 under the old rules.
The increase took place against a backdrop of change for the National Agency for Medicines and Medical Devices of Romania (NAMMDR). Pink Sheet
reported this week that the agency is set to undergo a reorganization to enable it to take on more work stemming from Brexit. The handling of the extra work and associated increase in staff numbers was cited as a reason why industry fees may increase.
NAMMDR is not one of the first nine countries to enter into a memorandum of understanding with the Dutch Medicines Evaluation Board that aims to boost regulatory capabilities in smaller member states, thereby enabling them to take on some of the work previously performed by MHRA. Yet, the broader changes in Europe are affecting the agency.
Outward signs of the change in NAMMDR’s role in the European regulatory landscape are already evident. Last year, Romania served as the rapporteur on two initial marketing authorization filings to the European Medicines Agency and was an assessor in three multinational teams.
That marked an uptick in Romania’s role. In 2017, Romania was co-rapporteur on four filings but did not take the lead on any submissions. Across 2015 and 2016, Romania had no formal involvement in the assessment of initial marketing authorization filings.
, Pink Sheet
Swissmedic Tightens Requirements for Authorization Application Documentation
The Swiss Agency for Therapeutic Products (Swissmedic) has adopted more precise documentation requirements for its simplified approval procedure. Swissmedic now wants separate proof of 10-year authorization of active substances and authorization of reference medicinal products in the EU.
Swiss officials detailed the change in guidance on documentation requirements for the submission and simplified authorization of medicinal products. Swissmedic adopted the guidance at the start of the year when the simplified procedure it describes came into force. The simplified procedure gives Swissmedic the power to streamline the authorization process in certain circumstances.
One stipulation is that the drug in question must have been authorized for at least 10 years in one or more EU or European Free Trade Association (EFTA) countries.
Under the revised guidance, applicants must provide “separate proof of 10-year authorization of active substance and authorization of reference medicinal product in EU/EFTA.” Swissmedic said the change makes the documentation requirements more precise.
The Spanish Agency of Medicines and Medical Devices
(AEMPS) has issued an alert about automatic external defibrillators distributed with fake CE marks. AEMPS learned of the situation from its equivalent in the Netherlands. AEMPS Notice