Euro Roundup: EMA posts guidance on preventing microbial contamination of non-sterile products
The European Medicines Agency (EMA) has released guidance on technical and organizational measures that companies should consider to prevent microbial contamination of non-sterile products.
For non-sterile treatments, opportunistic microbes in the final formulation or multi-antibiotic-resistant microbes can pose a hazard for the product or the patient. Manufacturers’ processes, particularly related to ensuring adherence to cleaning and gowning protocols, are closely linked to the risk of non-sterile medicinal products being contaminated by microbes.
That fact led EMA to create a question-and-answer document about measures to minimize the risk of product quality defects. The agency stressed the importance of cleaning equipment in accordance with validation principles. Manufacturers should explain critical cleaning procedures thoroughly in standard operating procedures and document them properly during execution, EMA said.
The Q&A, which EMA added to broader advice on following good manufacturing practices (GMPs) and good distribution practices, features two questions. One question covers organizational measures, giving EMA an opportunity to explain how the outcome of the risk management process should inform policies on the use of gloves and face masks, as well as the disinfection of gloves before entering critical areas.
Potential specific policies include regular, practical training and assessment of employees who perform gowning and cleaning, as well as education about correct behavior during production and other critical activities. Personnel hygiene and health status should be closely monitored and reviewed, EMA said, and environmental monitoring should be in place.
EMA’s other question covers further measures that manufacturers should take into consideration. As well as implementing organizational measures, manufacturers should consider factors such as the design and use of the facility and equipment, material flow, and microbiological control process characteristics in relation to established limits.
The agency’s advice is built on GMP guidance. EMA highlighted a section of GMP guidance that stresses the significance of protecting products and materials from microbial and other types of contamination at every processing step. That section lacks specific details. EMA also cited the quality risk management principles in the GMP guide as a touchstone for preventing contamination.
European Commission updates Q&A on safety features for human medicinal products
The European Commission has updated its Q&A on safety features for human medicinal products, adding a question about access to end-user information and revising its responses to several existing queries.
Safety features are unique identifiers and anti-tampering devices put on packaging to show that a drug is authentic and has not been interfered with along the supply chain. The Commission created a document to answer frequently asked questions about safety features.
Version 22 of the document, which the Commission published late last week, features a new question about whether national competent authorities (NCAs) should have access to all end-user information in the audit trail, including the names and addresses of end-users in another Member State.
The Commission confirmed that NCAs should have full access to all audit-trail data upon request. The data accessible by NCAs includes “information such as the corporate name and address of wholesalers and persons authorized or entitled to supply medicinal products to the public, who are involved in verifying the authenticity and decommissioning of a unique identifier,” the Commission said.
Other changes include the expansion of the Commission’s response to a question about the mandatory specifications for anti-tampering devices. The integrity of the device “should indicate whether the packaging has been opened or altered since it left the manufacturer, thereby ensuring that the content of the packaging is authentic,” the Commission said.
Swissmedic publishes eCTD implementation guide ahead of switch to new standard
The Swiss Agency for Therapeutic Products (Swissmedic) has released an implementation guide for the electronic Common Technical Document (eCTD) in preparation for switching to a new standard.
Swissmedic aims to complete the technical implementation of eCTD v4.0 by the end of 2026 and, after performing pilot tests, to start using the standard in 2027. The new standard will support compatibility of Swiss requirements for authorization applications with other regulatory authorities, Swissmedic said. The agency will continue to support the current eCTD v3.2.2 standard alongside v4.0 for several years.
To support the transition, Swissmedic has published a guide that covers the technical requirements and how to develop software applications for generating valid submissions in Switzerland. The package includes an implementation guide, lists of the required controlled vocabulary, and validation criteria.
Swissmedic plans to continuously refine and update the texts as it develops its eCTD review solution. The agency aims to release the final version by the start of next year at the latest and respond to frequently asked questions in spring 2027.
European authorities address concerns about missing clinical trial results in CTIS
EMA and other European authorities have responded to a report that compliance with the Clinical Trial Information System (CTIS) reporting requirements is “weak.”
Last month, Health Action International (HAI) publicized a preprint paper that found sponsors of half of the 234 clinical trials legally required to report results failed to comply with the requirements. Problems included incomplete and late submissions. HAI published recommendations for how EMA and NCAs can improve compliance.
Responding to a letter from groups including HAI, EMA, the Commission, and the Heads of Medicines Agencies outlined how they are trying to “further increase and monitor compliance with the publication requirements.”
The actions, some of which address HAI’s proposals, include using CTIS to alert sponsors of obligations to submit results and layperson summaries. European authorities recently supplemented the alerts with email notifications to CTIS users. Other actions include developing enhanced monitoring capabilities and revising training materials for sponsors.
EMA releases guidance on showing bioequivalence to Novo Nordisk’s semaglutide
EMA has published guidance on how developers of off-patent versions of the GLP-1 receptor agonist semaglutide can show bioequivalence to Novo Nordisk’s blockbuster branded products.
The agency provides product-specific bioequivalence guidance to help applicants meet the expectations of European regulators, particularly for generic applications. Off-patent versions of semaglutide, which could be classed as generics or biosimilars, have begun to come to market in parts of the world, and the drug is expected to lose exclusivity in some European countries by the end of the decade.
EMA’s guidance covers how to show bioequivalence to injectable semaglutide delivered at doses up to 2.4 mg using pre-filled pens and Novo’s FlexTouch device. The newly approved 7.2-mg semaglutide dose is missing from the list of formulations covered by the guidance.
The guidance details EMA’s expectations for the design of bioequivalence studies and the situations in which it will waive the requirement to run a pharmacokinetic bioequivalence study.
Other News:
EMA and the European Innovation Council and SMEs Executive Agency (EISMEA) signed a letter of intent about helping innovators better understand EU regulatory requirements. EISMEA, which manages the European Innovation Council, has worked with EMA since 2021 to support life science innovation. The cooperation covers training, awareness-raising, outreach, and support services. Press Release
The German Parliament passed a bill to control spending on health insurance. EFPIA, a trade group that represents large pharma companies, said the healthcare reforms “send a concerning signal about how Germany values its role as a leader in pharmaceutical innovation and the significant benefits it enjoys from a thriving industry.” EFPIA Notic
