Euro Roundup: EMA seeks feedback on planned changes to guidance on biosimilar efficacy studies
The European Medicines Agency (EMA) has released a draft concept paper on planned changes to its guideline on similar biological medicinal products.
Last revised in 2015, the guideline outlines general principles for biosimilars. The document provides an overview of what biosimilars are, plus information on the choice of reference product and principles for establishing biosimilarity. Under the guideline, companies must run comparability studies to “generate evidence substantiating the similar nature, in terms of quality, safety, and efficacy.”
Major progress in the analytical sciences and regulatory field of biosimilars has prompted EMA to rethink its requirements. In March, EMA’s Committee for Medicinal Products for Human Use adopted a reflection paper on a tailored approach to biosimilar development. The paper reflected experience that comparative efficacy studies (CES) generally do not add pivotal information for biosimilarity assessment. That experience led EMA to outline scenarios in which it could waive the need to perform CES.
Building on the reflection paper, EMA’s Biosimilar Working Party (BMWP) recommended revising the guideline on similar biological medicinal products to provide updated high-level guidance on CES. The update will cover the necessity and utility of CES, taking into account the scientific considerations addressed in the reflection paper, the international M18 guideline, and recent regulatory experience.
Because the reflection paper is available “with several regulatory procedures following immediately,” EMA does not expect the updated guideline to have a major scientific impact on biosimilar development. Rather, the update will align the guideline with the reflection paper and strengthen the regulatory basis for biosimilar development while taking global harmonization work and experience of CES-free approvals into account.
The reflection paper is one of two primary triggers for the update. The other trigger is the European Union’s proposed pharmaceutical law, which will change the legal-regulatory definition of a biosimilar. EMA wants to update the guideline to reflect the new legal definitions and associated high-level data requirements for biosimilars.
EMA is seeking feedback on the draft concept paper until 31 October. BMWP aims to publish a draft revision of the guideline in the second quarter of 2027 and to adopt the final document in 2028. EMA sees the need to evaluate updated definitions in the pharma legislation as the main risk of delay.
Coordination group posts principles on using AI to create clinical assessment dossiers
The Coordination Group on Health Technology Assessment (HTACG) has published general principles on using artificial intelligence (AI) to prepare dossiers for joint clinical assessments (JCAs).
Under the HTA Regulation, health technology developers create and submit dossiers used by European authorities in JCAs to evaluate the relative effectiveness and safety of new medicines. In recent months, authorities have completed JCAs of drugs from Amgen, Ipsen, and PharmaMar. Two JCAs have been withdrawn because of incomplete dossiers, while other assessments are ongoing.
Last week, HTACG published general principles addressing the potential for AI use to compromise “the completeness, methodological quality, and rigor of a JCA.” The coordination group acknowledged that AI could make JCA processes more efficient, but the risks led it to offer advice on using the technology.
“AI should be used in an accountable way and transparently to ensure its outputs are accurate and reliable, thus upholding the scientific quality of all the steps that lead to a JCA,” HTACG said.
Health technology developers are accountable for decisions about when and how AI is used, the impact it has on the evidence synthesis, and the validity of any output resulting from the technology, HTACG said. Responsibility for ensuring AI use complies with the law, including on copyright and data protection, falls on health technology developers. Human oversight is essential.
“It is the understanding of the HTACG that human oversight should be maintained throughout any steps which are assisted by AI in the preparation of the JCA dossier,” HTACG said. “None of the steps in the dossier preparation or analysis process should be fully automated without a human being ultimately responsible for the quality and accuracy.”
HTACG expects applicants to clearly document AI use in their dossiers, including by specifying all steps that were assisted by the technology. Outputs or judgments that are either AI-generated or AI-informed should be identified. HTACG wants to know the name, version, and date of the AI tool the applicant used, the developer of the technology, and the specific purposes it was used for.
European Commission publishes expert decision on dual-chamber leadless pacemaker
The European Commission has shared an expert decision on a notified body’s review of a dual-chamber leadless pacemaker.
Because of the risks posed by the device, independent experts reviewed the notified body’s clinical evaluation assessment report. The expert panel confirmed that the notified body had performed a thorough, adequate, and sufficiently detailed review, including by assessing qualitative and quantitative aspects of clinical safety and confirming that the manufacturer’s evidence matched its intended purpose.
The panel agreed with the notified body that the manufacturer’s clinical evidence is consistent with the post-market clinical follow-up (PMCF) plan. The experts added the proviso that safety and performance threshold values and acceptance criteria must be reviewed constantly during the PMCF activities. All the experts agreed with the consensus reached by the panel.
Special consideration should be given to certain serious adverse events during post-market surveillance, the expert panel said. Available data suggest atrial fibrillation and dislodgement may be more common for the dual-chamber device than for a single-chamber pacemaker. The expert panel accepted that the complication rate could be compatible with the state of the art for leadless pacemakers but recommended surveillance.
The adverse event data come from the AVEIR DR i2i study. The clinical trial evaluated AVEIR DR, Abbott’s dual-chamber leadless pacemaker system. Abbott received a CE mark for the medical device, the first of its kind, in 2024.
UK MHRA approves first lower-carbon beclometasone inhalers for asthma patients
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has claimed the world’s first authorization of pressurised metered-dose inhalers (pMDIs) using a next-generation propellant.
Chiesi updated 100μg and 200μg doses of its Clenil Modulite inhalers to use HFA-152a as a propellant. Like the older versions, the inhalers deliver beclometasone dipropionate for the maintenance treatment of asthma in adults and children. The change affects the propellant used to deliver the inhaled doses.
Older versions of the Clenil inhalers contain the propellant HFA-134a, which has a high global warming potential. Inhalers account for 3% of the UK health service's carbon footprint. Recognizing that propellants such as HFA-152a have a lower global warming potential, inhaler manufacturers, including Chiesi and GSK, are implementing changes to reduce their products’ climate impact.
MHRA approval of the updated Clenil inhalers positions Chiesi to start providing the revised pMDIs in the UK this year. Chiesi calculates its propellant transition will cut the carbon footprint of its beclometasone products by up to 90%. In December, the company said it intended to fully transition its pMDI portfolio in the UK to the new propellant by the end of 2027.
Other News:
EMA published a signal assessment report on neurodevelopmental disorders with paternal exposure to valproate and related substances. The report covers the evidence and debate that informed EMA’s position on the risks posed by the medicines. EMA Report
