Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
France’s ANSM Issues Warning About NSAIDs Following Safety Review
France’s National Agency for the Safety of Medicines and Health Products (ANSM) has published a warning about the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients suffering from infectious diseases. ANSM issued the warning after analyzing almost 20 years of real-world safety data on the use of the NSAIDs ibuprofen and ketoprofen.
Ibuprofen and ketoprofen are used to treat fever and mild-to-moderate pain and, as such, may be considered for use by patients and healthcare professionals in the management of symptoms caused by infections. The use of NSAIDs in these contexts is associated with complications, though, such as the severe bacterial skin conditions that can occur when the painkillers are given to people suffering from chickenpox. To assess these risks, ANSM reviewed adverse event reports going back to 2000.
ANSM selected 337 cases of infectious complications linked to ibuprofen and a further 49 cases tied to ketoprofen for analysis based on their severity and the lack of risk factors and comorbidities. The selected cases included reports of infections of the skin and soft tissue, blood, pleuropulmonary and neurological systems and other parts of the body. Some of the infections led to patient deaths.
The infectious complications were mainly associated with Streptococcus
and occured after two to three days of treatment with NSAIDs, including when they were given with antibiotics. The NSAIDs were given by healthcare professionals or self-administered by patients to treat conditions including fever, insect bites and other benign inflammatory skin lesions and respiratory conditions. ANSM also found people with chickenpox continue to take NSAIDs, despite them being contraindicated.
ANSM emerged from the analysis with concerns that existing infections are exacerbated by the use of NSAIDs. In response, the French regulator has issued a reminder about the safe use of NSAIDs to patients and healthcare professionals and passed the findings on to its counterparts across Europe. ANSM hopes to spark a European Union-wide analysis of the safety of NSAIDs.
UK Trials Remote GDP Assessments of Secondary Distribution Facilities
The Medicines and Healthcare products Regulatory Agency (MHRA) is trialling remote assessment of some distribution facilities. MHRA thinks the office-based inspection program will increase oversight, reduce burdens on some companies and free up regulatory resources for assessing high-risk sites.
The program, called the Office Based Evaluation and Risk Assessment (OBERA), will target companies that have large head offices that perform most of their wholesale activities and a number of smaller sites that perform a limited range of tasks regulated under good distribution practices (GDPs). These small satellite sites are the focus of OBERA.
For the pilot, the United Kingdom’s MHRA plans to contact companies with more than 100 sites. Through gateway inspections similar to the standard GDP review, MHRA will assess whether these companies are eligible to participate in OBERA. The criteria assess the activities and independence of satellite sites.
“The Gateway Inspection performed at the head office site is designed in such a way that a company has the opportunity to demonstrate to the inspector(s) that the Responsible Person has good control over the GDP activities being performed at the remote satellite sites and that these sites are compliant,” MHRA wrote.
If a company meets the criteria, MHRA will ask it to complete questionnaires for around 25% of its sites. MHRA will inspect selected satellite sites as a safeguard, but most facilities will be cleared by a remote assessment.
Once the pilot is complete, MHRA plans to expand OBERA to cover companies with fewer sites but similarly centralized operating models.
Germany Approves Cultivation of 7,200 kg of Pharma-Grade Cannabis
Germany’s Federal Institute for Drugs and Medical Devices (BfArM) has approved the cultivation of 7,200 kg of pharmaceutical-grade cannabis. The regulatory clearance is intended to lessen Germany’s reliance on imports of medicinal cannabis.
BfArM put out a tender for 10,400 kg of cannabis — 58% more than originally planned — last year and spent the first few months of 2019 evaluating the 79 bids it received. The agency split each 2,600 kg annual allocation into 13 lots of 200 kg. BfArM previously said offering 200 kg lots would enable small producers to enter the market and prevent over reliance on a small number of companies.
However, so far, BfArM has awarded almost 70% of the allocation to two companies. Aurora Produktions has won the contract for five lots, while Aphria Deutschland has picked up a further four. The agreements clear the two businesses to produce 7,200 kg of cannabis in Germany over four years.
BfArM is yet to award the remaining four lots because an unsuccessful bidder requested a review of the decision. As the case is ongoing, BfArM cannot share details or commit to a resolution date.
The agency expects the first harvest to happen in the fourth quarter of 2020. Cannabis will continue to be imported into Germany once internal production begins, but the country will be less reliant on external sources.
Finland on Track to Complete Transfer of Medical Device Oversight in 2019
The Finnish Medicines Agency (Fimea) is on track to take on supervision of medical devices and other health technologies by the end of 2019. Fimea is set to take over the work from Finland’s National Supervisory Authority for Welfare and Health (Valvira).
Responsibility for medical device oversight in Finland has moved around over the past decade. The National Agency for Medicines (NMA) — the old name for Fimea — used to monitor the marketing of medical devices and their compliance with laws and regulations. That changed in 2009 when NMA transferred responsibility to Valvira.
Now, Valvira is transferring the responsibilities to Fimea. The transfer is underway and Fimea is on course to take charge of the work and related staff by the end of the year. In parallel, Finland is reforming the register for health care devices and equipment and expects to finish that process this year, too.
Once the device reform program is complete, Fimea plans to undertake similar initiatives involving the biobank and gene technology registers. These registers are part of the transfer of responsibilities for health technologies that is now underway.
EMA Fields Criticism of Preclinical ICH Guidance From Animal Protection Group
The European Medicines Agency (EMA) has fielded criticism of an International Conference on Harmonisation (ICH) guide to preclinical safety testing to support pediatric development. EMA will pass the negative feedback on to ICH for consideration in the revision of the document.
In the guide, ICH outlines when it thinks companies should perform juvenile animal studies (JAS) to provide safety data to inform the development of drugs for use in pediatric patients. Most of the comments sent to EMA when it released the guide for consultation broadly support ICH’s stance on JAS, but it also received some pushback.
“Considering that one of the stated key objectives of the guideline is to promote a reduction in the use of animals in accordance with the 3Rs principles, we have some serious concerns regarding ... the unsubstantiated support for JAS as a standard approach, rather than as a last resort option,” the International Council on Animal Protection in Pharmaceutical Programs (ICAPPP) wrote.
ICAPPP thinks the routine use of JAS may provide false assurances about the safety of medicines and cause unnecessary suffering of animals. The organization wants ICH to advise companies to consider non-animal tests before performing JAS.
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