EU Regulatory Roundup: EMA Starts Revising Guidance on Clinical Trials in Neonates
Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.EMA Starts Revising Guidance on Clinical Trials in Neonates
The European Medicines Agency (EMA) has published a draft concept paper on the investigation of medicinal products in neonates. EMA is revising its stance on testing drugs in newborn babies after interactions with sponsors identified shortcomings in the guidance it published on the topic in 2010.
In its 2010 guidance, EMA set down general principles for the investigation of medical products in term and preterm neonates. The guideline was in development for several years and underwent a public consultation before being finalized. Yet, in the years since the guideline was adopted, the same questions have come up again and again in EMA’s assessments of pediatric investigation plan (PIP) filings for products destined to be investigated and used in neonates.
The draft concept paper is the first step in an effort intended to address these questions and bring the text into line with current thinking about neonatal research and standards. In the draft, EMA lists 14 critical aspects it plans to address in the update to the guideline.
Some of the planned changes affect fundamental aspects of EMA’s position. Notably, EMA is planning to revise how it defines “neonate.” The current guideline defines neonates as “the group of children from birth up to and including the age of 27 days, including term and preterm neonates.” However, that definition is outdated. Today, a system based on postmenstrual age (PMA) that addresses enzyme and organ system development in preterm neonates is more widely used. In this model, the “neonatal age for preterm neonates is considered the age period up to 44 full weeks of PMA.”
Aspects of the rethinking of the neonate classification are reflected in other changes planned by EMA. The agency wants to see more focus on the differences in the maturation of organ and enzyme systems between neonatal subgroups, such as term, preterm and extremely preterm neonates. That subdividing of neonates is evident in another planned change to the assessment of differences in pharmacokinetics (PK), pharmacodynamics (PD) and dose finding between subgroups of newborns.
The way EMA wants sponsors to approach these activities is influenced by broader changes to the thinking about neonate research that have happened since the 2010 guideline. As EMA notes, dose selection, extrapolation of efficacy, modeling and simulation and PK/PD extrapolation have “evolved significantly over the last years and must be correctly addressed.”
Other planned changes include the placing of greater emphasis on the study design. EMA wants sponsors to design clinical trials that try to differentiate between the effect of the treatment and the various confounding factors common in neonates. The agency is planning to tackle challenges related to excipients, the need for long-term outcomes data and the validation of biomarkers, too.
EMA is accepting feedback on the draft until 16 December.
Concept Paper
Scotland Stops Transvaginal Mesh Procedures With Immediate Effect
The Scottish government has stopped the use of transvaginal mesh to treat pelvic organ prolapse and stress urinary incontinence. With one exception, the action bans procedures involving transvaginal mesh until a protocol that limits their use to rare circumstances is in place.
Scotland has been at the forefront of efforts to restrict the use of tranavaginal mesh in the United Kingdom. In 2014, the government asked the National Health Service to stop using the devices. Two years later, another 400 women had undergone transvaginal mesh procedures, prompting Scottish politicians to criticize how the UK Medicines and Healthcare products Regulatory Agency’s (MHRA) was handling the situation.
Politicians in Westminster have since followed the lead of their peers in Scotland, leading to strong temporary restrictions on the use of vaginal mesh in the treatment of stress urinary incontinence across the UK.
Scottish officials have decided the UK-wide action does not go far enough, though, leading them to ban use of the implant in pelvic organ prolapse and stress urinary incontinence procedures. The only exception to the Scottish ban are women who are currently awaiting treatment with mesh under “the treatment time guarantee.” Provided these women give clear informed consent, their treatments can go ahead.
In all other cases, use of transvaginal mesh is on hold until a new protocol is in place. The protocol is expected to restrict the use of transvaginal mesh to exceptional circumstances and otherwise impose limitations that mean use of the implants is likely to be limited even after the ban is lifted.
“Should the halt be lifted, transvaginal mesh would be available in the NHS in Scotland only under the restricted use protocol, which would require the health board’s medical director ... to consider and agree each case individually, taking account of the clinical evidence, and would be subject to evidenced, informed and voluntary consent being obtained from the woman,” Jeane Freeman, the Scottish cabinet secretary for health and sport, said in a statement to parliament.
Government Statement
Denmark Improves Score on Regulatory Agency Benchmarking Initiative
The Benchmarking of European Medicines Agencies (BEMA) has scored the Danish regulator 4.5 out of 5 in its latest assessment of the performance of national competent authorities (NCAs). BEMA gave the Danish Medicines Agency (DKMA) a score of 3.9 when it last assessed it in 2014.
Since 2004, the Heads of Medicines Agencies have periodically benchmarked NCAs against indicators related to management systems, the assessment of marketing authorization applications, pharmacovigilance activities and inspection services. BEMA began its latest cycle of assessments in 2015 and expects to have visited 47 agencies by the end of the month.
The timelines of the previous three cycles of BEMA assessments suggest there will be a lag between the end of the visits and the publication of the final report. However, DKMA already knows its score and is promoting its improvement over the prior assessment.
“The BEMA top score given to the Danish Medicines Agency is a sign that Denmark possesses good assets in an area that is developing rapidly, for example with the use of big data in the development of new medicine, precision medicine tailored to the individual citizen and a new framework for more efficient clinical trials,” Ellen Trane Nørby, the Danish health minister, said.
BEMA’s third and fourth assessments span a period of change for DKMA. Late in 2015, Denmark re-established DKMA and set out to turn it into a leading European drug regulatory agency. That led DKMA to make multiple changes, including the hiring of leaders with international experience and the initiation of a scientific advice service.
DKMA Notice
Other News:
EMA has published a summary of its third industry stakeholder platform on research and development support. At the event in May, EMA and the industry discussed orphan drugs, the review of digital technology proposals in medicine development programs and a framework for the co-development of therapies and companion diagnostics. EMA Summary
EMA’s Committee for Medicinal Products for Veterinary Use (CVMP) has adopted two scientific advice reports. The reports provide initial advice on safety and efficacy issues related to medicinal products for cats and dogs. CVMP also agreed to extend the marketing authorizations for Chanelle Pharmaceuticals Manufacturing’s Inflacam and Rheumocan. EMA Notice
MHRA has issued a notice about Cadiasun Pharma’s Caspofungin 70mg powder concentrate for solution for infusion. The notice relates to an error on the patient information leaflet. MHRA Notice