Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA Refines Paper on Frailty of Senior Trial Participants After FDA Feedback
The European Medicines Agency (EMA) has refined its reflection paper on the frailty of senior clinical trial participants after receiving feedback from regulators in the United States. EMA’s final version of the paper incorporates significant changes proposed by the US Food and Drug Administration (FDA).
Members of EMA’s Geriatric Expert Group released the document for consultation back in 2015, at which time its scope covered all forms of frailty. The goal was to encourage sponsors to assess the baseline frailty characteristics of trial subjects. That done, sponsors could assess whether frailty parameters correlate with outcomes and, in doing so, follow ICH advice on generating safety and efficacy data tailored to specific subpopulations in the real world.
The consultation closed in 2016, but the process of getting a final text approved by the Committee for Medicinal Products for Human Use (CHMP) has progressed slowly. Now, though, EMA has finalized the document and shared the feedback that influenced its revisions.
FDA submitted the feedback behind some of the headline changes, including the decision to narrow the focus to trial participants aged 65 years and older. One goal of the reflection paper is to recognize that frailty only loosely correlates with a person’s age, and therefore more refined assessments of baseline characteristics are needed. However, with FDA questioning whether other age groups need to undergo baseline frailty tests, EMA has limited the scope of the document to seniors.
EMA also heeded FDA’s advice about the effect the reflection paper will have on investigators and participants in clinical trials. FDA noted each frailty assessment will take 10 to 15 minutes. If several frailty assessments are required, that could add significantly to the burden on subjects and sites, potentially deterring both from participating in studies. The deterrent will be even greater if sites are unfamiliar with the assessments.
“Additional training likely will be needed for the clinical investigation staff because many of the instruments require specific training to properly perform the assessments. For example, the [short physical performance battery] is currently only included in geriatric fellowship training, but not other specialties,” FDA wrote in its feedback.
The final version takes these concerns into account. EMA included ease of use, time required and ease of investigator's training on a newly added list of criteria for choosing the right assessment tool. That change goes some way to appeasing the concerns raised by other respondents, including Regeneron. The drug developer said it found the “concept and recommendation of applying baseline frailty status ... challenging and not practically applicable in both clinical research.”
Regeneron’s concerns are based, in part, on the feasibility of asking investigators to use assessment tools they are unfamiliar with, such as if cardiovascular researchers had to use neurocognitive scales. Another big change in the final document addresses that specific concern by narrowing the focus of the reflection paper to physical frailty only.
EMA said the change improves the focus of the paper but it goes against feedback received from other respondents, including the FDA. The US agency praised EMA for including “other domains of frailty beyond physical” in the document, calling it a “notable strength” of the reflection paper.
, Collated Feedback
MHRA Posts Warning After Manufacturer Ignores Withdrawal of CE Mark
The Medicines and Healthcare products Regulatory Agency (MHRA) has warned that a company is continuing to supply nebulizers despite losing its CE mark. MHRA is advising people to stop using the Aquilon Medical nebulizers immediately, as they are not subject to required regulatory oversight.
AFP Medical, the manufacturer of the nebulizers, used to hold a CE mark but it was withdrawn. At that point, the company should have stopped supplying the products in the European Union. Officials in the United Kingdom have evidence AFP continued to sell the devices, though, resulting in more than 8,000 products coming to market without the necessary regulatory clearance and oversight.
“We cannot guarantee they have been manufactured to an appropriate standard. These devices deliver potential life-saving treatment and it is vital they operate correctly when needed. We are taking action, as a matter of priority, to make sure people are aware the CE mark has been withdrawn and that these devices should not be used and should be disposed of,” John Wilkinson, MHRA’s director of medical devices, said.
MHRA wants people with affected nebulizers to stop using them immediately and dispose of the device. Products that came to market as far back as 2015 are affected by the MHRA warning. The packaging for the devices carries the CE mark, but MHRA said AFP had not been subjected to the regulatory oversight needed to obtain this clearance.
France Shares Recommendations on Naming of Medicines
France has released recommendations about the naming of medicines. The national drug regulator posted the advice to cut the risk of one medicine being confused for another and other errors.
Officials fear ill-considered names can cause errors in target populations, indications and other areas, while also resulting in mixups in drug selection. To mitigate these risks, France’s National Agency for Medicines and Health Products Safety (ANSM) has published an eight-page document explaining the steps applicants for approval should take to ensure their products have appropriate names.
The basic advice is to avoid names that could be confused with those of other drugs, medical devices, cosmetics and food supplements. ANSM provides specific details about how to achieve this goal. The agency expects applicants to consider whether a proposed name could resemble another brand when written by hand or spoken. If so, the name should be avoided.
ANSM is also seeking to guard against deliberate bad naming practices. The advice includes a section on the importance of avoiding names that give a misleading impression of the qualities, properties or composition of the product, either when written or spoken. Similarly, words such as “strong” and variants on them are prohibited, both in French and English. ANSM prefers one-word names.
The recommendations refer to naming practices adopted by the World Health Organization and are designed to complement EMA guidance on the topic. ANSM established its position after running a consultation.
The Federal Institute for Drugs and Medical Devices
(BfArM) has issued a warning about fake versions of Roche
’s CellCept. Pharmacies and wholesalers discovered the counterfeit copies of the drug to prevent acute transplant rejection reactions. BfArM and Roche later learned the counterfeits feature genuine batch numbers. At least one of the batches contains genuine CellCept imported from elsewhere in Europe and repackaged in falsified German-language packaging. BfArM Note
is recalling inhalers from the UK. The recall affects two batches of Ventolin Accuhaler
inhalers that may fail to deliver the full number of doses owing to a manufacturing fault, MHRA
said. The agency is concerned the inhalers may not provide emergency relief of asthmatic symptoms. GlaxoSmithKline is also recalling a lot of Seretide Accuhaler
. MHRA Notice
has warned consumers about a “natural” Chinese medicine that contains an undisclosed steroid and two antifungal ingredients. The agency wants people to stop using the product, Yiganerjing Cream, immediately. The product is marketed for the treatment of eczema, psoriasis, rosacea and other skin conditions. MHRA Notice