A Master UDI-DI becomes obligatory for spectacle frames and lenses
Commission Delegated Regulation (EU) 2025/1920, which was published on 23 September 2025, has introduced an obligation to assign a Master UDI-DI to spectacle frames, spectacle lenses and ready-to-wear reading spectacles. A Master UDI-DI must be assigned to frames sharing the same design parameters, to lenses with the same combination of design parameters, and to ready-to-wear reading spectacles that products sharing same combination of design parameters. Changes to these parameters will require a new Master UNI-DI. The obligations was introduced through an addition to Annex VI Part C to the MDR.
The new obligations imposed by the Regulation will apply from 1 November 2028. However, in MDCG 2025-7 https://health.ec.europa.eu/document/download/ad6ae143-baa2-451a-8c5e-0c5d22983e88_en?filename=mdcg_2025-7_en.pdf concerning Timelines of the implementation of ‘Master UDI-DI’ to contact lenses
and spectacle frames, spectacle lenses and ready-to-wear reading spectacles, the MDCG urges manufacturers to assign Master UDI-Ds as soon as possible.
The Medical Device Coordination Group (MDCG) has endorsed a new draft Q&A document on trend reporting under the EU Medical Device Regulation (MDR) and the in vitro diagnostics Regulations (IVDR) (Trend Reporting Q&A (MDCG 2025-X)). Article 88 of the MDR and Article 83 of the IVDR provide a framework through which manufacturers should report statistically significant increases in the frequency or severity of incidents that are not serious incidents that could have a significant impact on the benefit-risk analysis.
The draft Guidance, which is in the form of Questions and Answers, complements MDCG 2024-1 on Guidance on the vigilance system for CE-marked devices. It discusses, among other things, how manufacturers should assess what constitutes “a significant impact on the benefit-risk analysis”. The draft provides that, within the context of trending, a “significant increase” should be determined by comparing the foreseeable frequency and/or severity of the incidents with the statistical methodology set out in the technical documentation. The draft includes practical advice on what documentation should accompany trend reporting and how trend reporting is linked to the manufacturer’s Post Market Surveillancec plan and its QMS.
The draft Guidance has been released for stakeholder review. It is not yet clear when the final version of the Guidance will be agreed.
New draft Guidance on trend reporting
Update to the Borderline Manual provides both guidance on product classification and insight into the Working Group thought process.
The European Commission has published an updated version of the Manual on Borderline and Classification for Medical Devices, commonly referred to as the Borderline Manual.
There are six new additions to the Manual, four of which relate to products which the Working Group concludes are not appropriate for classification as a medical device. The route by which the Working Group came to its conclusion concerning the appropriate classification of the products under review demonstrates the Group’s related thought process. Its associated conclusions could, in some instances, be applied in determining the appropriate classification of other products.
The update includes new opinions concerning the following products:
Red blood cell additive solutions containing adenine are to be considered Class III medical devices. The product could have a metabolic mode of action or a pharmacological mode of action (or both) as defined in MDCG 2022-5. As an ancillary medicinal product, red blood cell additive solutions containing adenine fall within Rule 14 Annex VIII of the MDR;
Medical examination table covers are considered medical devices. This is because their intended purpose is to ensure a good level of hygiene and to prevent the transmission of infectious agents, which can be easily transferred from patient to patient through contact with a common surface;
Dual-action cream with menthol and capsaicin is not considered a medical device. The Working Group concluded that both substances have a pharmacological mode of action. In its conclusion, the Working Group recalled that it is the manufacturer that bears the burden of proof for the non-pharmacological, non-immunological, or non-metabolic effect of their product;
A mobile sterile air systems is not considered a medical device. This is because, although the system enables an appropriate environment to perform medical interventions, it does not itself have a medical purpose;
Lactose vaginal tablets are not considered a medical device as they achieve their principal intended action by metabolic means in or on the human body;
Microabrasion dental stain removers (tooth whitening), classification of which has been the subject of some debate in recent years, are not considered a medical device. The Working Group concluded that products used for improving the appearance of teeth do not comply with the legal definition of medical device established in the MDR.
As with previous versions, Version 4 of the Manual underlines that the document represents the view of the EU Member State members of the Borderline and Classification Working Group, a subgroup of the Medical Device Coordination Group (MDCG) and that the views are not legally binding. Experience indicates, however, that the opinions presented in the Manual can influence the approach of both competent authorities and notified bodies to appropriate classification, not only of the products that are the subject of Committee review, but also products that could be perceived to be equivalent.
EMA Unveils ERATO its new AI Tool improving Pharmacovigilance Signal Detection
Among the initiatives discussed by the European Medicines Agency (EMA) in its recently published annual report on 2024 activities was
Its new AI tool Enhanced Review of Abstracts with Transformer models (ERATO). The purpose of ERATO is to reduce by an estimated 80% to 90% the roughly 200,000 abstracts the EMA Pharmacovigilance Office reviews every year. This could save more than 0.5 FTE (full time eqivalent) per week. The tool screens scientific literature publications to detect safety signals, which are new or known adverse events that may be caused by a medicinal product and require further investigation. In a related commentary, an EMA official commented that ERATO had also resulted in the “secondary benefit” of helping the EMA to establish a more robust tracking system for the review of safety signals identified during the screening process.
Swissmedic reduces review times for generic medicinal products
Swissmedic has shortening the procedural time limits for applications for new authorisation of generic medicinal products. This change is part of the continuous development of the procedure under Art. 13 TPA (Changes to the guidance document Time limits for authorisation applications). The new time limits shorten the procedure for applications for authorisation of generic medicinal products to a total of 195 days. The new time limits took effect on 1 September 2025.
The European Commission, the Heads of Medicines Agencies (HMA), and the EMA have jointly developed two new targets for clinical trials, to monitor progress against the ambition of making the EU a more attractive destination for clinical research and to improve timely access to innovative medicines for patients. The aim is that, in the coming five years:
An additional 500 multinational clinical trials are added to the current average of 900 that are already authorised each year (i.e. an estimated additional 100 per year);
Two thirds (66%) of clinical trials should begin recruiting patients within 200 calendar days or less from the date of submission of an application for approval of the clinical trial. This is in comparison to the current 50% of clinical trials.
These goals build on the Authorities’ ongoing efforts to create a more supportive environment for clinical research. A key part of this is the Accelerating Clinical Trials in the EU (ACT EU) initiative which seeks to optimise how clinical trials are designed and run. Although the acronyme ACT is included in its title, ACT EU is not a legislative provision. It is rather an initiative that is intended to support smarter clinical trials through regulatory, technological and process innovation. The regulatory bodies launched ACT EU in 2022 with the aim of creating a more favorable clinical trial environment. It uses recommendations from the EU’s medicines agencies network strategy and the European Commission’s Pharmaceutical strategy for Europe to propose regulatory changes that encourage clinical trial research.
European Commission sets new clinical trial targets for the EU
EMA develops a Concept Paper on the development of guidance concerning use of external controls for evidence generation in regulatory decision making
The European Medicines Agency (EMA) has published a Concept Paper on the Development of a Reflection Paper on the Use of External Controls for Evidence Generation in Regulatory Decision Making (Concept paper). The Concept Paper recalls the current lack of specific regulatory guidance concerning the use of external controls to support regulatory decision making in the EU. It outlines general principles for assessing when external controls could be appropriate for regulatory decision making. These will be included in the Reflection Paper to be prepared. The principles include definition of external controls, appropriate clinical and regulatory setting and minimal requirements for external controls, operational and feasibility aspects, planning, design, conduct, analysis and reporting of studies for which external controls are used, error control, sample size and data quality. The Reflection Paper will not address issues such as use of historical data for contextualisation, external control data used to augment randomised controlled trials, and indirect comparisons using a network meta-analysis. Adoption of the Reflection Paper by the EMA’s Committee on Human Medicinal Products (CHMP) is expected by Q2 2027.
ICH proposal for Guidelines for Extractables and Leachables
The ICH proposal for Guidelines for Extractables and Leachables has been published on the European Medicines Agency (EMA) website https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q3e-guideline-extractables-leachables_en.pdf. The purpose of the draft Guideline is to provide a global framework for managing leachables in pharmaceutical products.
This draft Guideline presents a holistic framework and process for the assessment and control of leachable impurities to further expand the existing ICH guidelines on impurities, including impurities in new drug substances (ICH Q3A) and new drug products (ICH Q3B), residual solvents (ICH Q3C), and elemental impurities (ICH Q3D), as well as DNA reactive (mutagenic) impurities (ICH M7). The framework of this draft Guideline follows the principles of risk management as described in ICH Q9. While the draft Guideline includes materials characterization and process understanding, its primary purpose is to protect patient safety and product quality through assessment and control of leachables in the drug product. Due to rapid advances in materials engineering, device innovations, new manufacturing paradigms and novel therapeutic modalities, the aim is to provide principles and concepts that are forward looking within the scientific and regulatory landscape.
The draft Guideline expands existing ICH impurity guidelines and includes an multifactional risk matrix. The overall risk management process includes hazard identification, risk analysis and an integrated risk evaluation. The draft Guideline applies to the risk assessment and control of leachables in new drug products, including cell and gene therapy products. Drug-device combination products that require marketing authorizations and meet the definition of pharmaceutical or biological products also fall within the scope of the draft Guideline.
Organic leachables are the primary focus of this draft Guideline. Though recommended methodologies for elemental analysis are within the scope of the draft Guideline, the safety assessment of elemental leachables are addressed by ICH Q3D and thus out of scope for this draft. Products excluded from the scope of the draft Guideline include herbal medicinal products and crude non-processed products of animal or plant origin and products used during clinical research stages of development.
The draft Guideline recalls that leachables generally represent a subset of extractables. The concentration of each leachable is typically below that of the corresponding extractable from a well conducted extractables study. Once the extractable and leachable are established the draft Guideline recommends that a qualitative and quantitative correlation between the two be evaluated. Related purposes and procedures are discussed. The draft Guideline recommends incorporation of a Safety Concern Threshold to first establish a study-specific Analytical Evaluation Threshold (AET). This is the threshold at or below which a leachable would have a dose so low as to present negligible safety concerns from mutagenic and non-mutagenic toxic effects unless the leachable is identified as being a leachable of high concern.
Revision to EMA Alzheimer’s Trial Guideline
The European Medicines Agency Guidelines on the clinical investigation of medicines for the treatment of Alzheimer's Disease (AD) were last updated in 2018 (https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicines-treatment-alzheimers-disease-revision-2_en.pdf). The Agency has recently published a concept paper concerning future revision of these Guidelines https://www.ema.europa.eu/en/documents/scientific-guideline/concept-paper-need-revision-guideline-clinical-investigation-medicines-treatment-alzheimers-disease_en.pdf. The revisions are, in part, the result of recent advances in the field of AD, including the recent authorisation in the EU of a medicinal product for treatment of early-stage Alzheimer's Disease (AD) by targeting amyloid plaques, and experience from several marketing authorisation applications for early AD treatments. The Concept Paper includes proposals to include identified elements that would be “helpful in designing state of the art clinical trials in AD, including early AD, and enhancing drug development in the field.when developing clinical trials”. The EMA plans to release a draft CHMP guidance document for consultation not later than Q4 2026.
Updated Guidelines on the Variations Regulation - but not until January 2026
Following adoption of Regulation (EC) No 1234/2008 (the Variations Regulation), which applied from January 2010, the European Commission published related Guidelines in 2013. The Guidelines have not subsequently been updated. As a result, the revisions to the Variations Regulation that occurred in 2021 and 2024 are not reflected in the existing version of the Guidelines.
The new Variation Guidelines that were recently published reflect the 2024 amendment of the Variations Regulation (Commission Delegated Regulation (EU) 2024/1701 of 11 March 2024). This amendment introduced, among other things, procedures according to which marketing authorisation holders may submit “super groups” of the same Type IA variations related to different medicinal products. The 2024 Regulation also extended existing work sharing procedures, with all Type IB and II variations related to different medicinal products belonging to the same marketing authorisation holder required to be submitted with a single application. The Regulation entered into application in January 2025.
The new Guidelines will enter into application on 15 January 2026. Any variations submitted prior to that date, including those based on the 2024 amendment to the Variations Regulation, should, however, follow the 2013 guidelines. This approach is confirmed in related comments on the EMA website which underline that 15 January 2026 represents a single cut-off date for the entry into application of the new Guidelines. While, in light of the recent entry into application of the 2024 amendment to the Variations Regulation, it is tempting to seek inspiration from the new related Guidelines prior to submission of a variation the EMA position is clear. It requires that “Until 15 January 2026, marketing authorisation holders should continue to rely on the current Variations Guidelines and on the specific procedural guidance”. Seeking to rely on the new Guidelines before that date, however practical this may appear, may result in a refusal by the EMA to validate related submissions.
It is anticipated that, to assist marketing authorisation holders with the implementation of the new Guidelines, EMA will publish updated and new procedural guidance by the end of December 2025.
MDGC Publishes Guidance on Performance Studies for IVDs
The Medical Devices (Post-market Surveillance Requirements) (Amendment) (Great Britain) Regulations 2024 entered into force on 16 June 2024. The Regulations, which apply in Great Britain, introduce a new Part 4A to the existing Regulations governing post-market surveillance (PMS) requirements for medical devices. These include in vitro diagnostic (IVD) devices and active implantable medical devices.