Euro Roundup: EMA seeks feedback on approaches to qualifying novel, non-mutagenic impurities

The European Medicines Agency (EMA) has begun a consultation into the principles and methods for qualifying novel impurities.

EMA’s draft reflection paper focuses on non-mutagenic impurities in chemically synthesized medicines. The agency said the principles and methods should primarily be applied to impurities “arising from changed manufacturing processes, discovered after safety studies have been concluded or when higher levels need to be qualified and existing data from safety studies are not sufficient for qualification.”

Existing International Council for Harmonisation (ICH) guidelines address how to qualify non-mutagenic impurities. However, EMA said little guidance is available for qualifying impurities that fall outside the scope of those guidelines. The lack of advice is especially true when companies find novel impurities that were not present in batches used in development, according to the agency.

The paper lists key considerations for qualifying impurities, starting with a general outline for assessing the risks and continuing with ways to determine an impurity's toxicological properties. EMA wants companies to consider in silico, in chemico, and in vitro approaches to impurity qualification that use existing data or non-animal models. In vivo studies are “generally discouraged,” EMA said, but the reflection paper describes how to run animal studies when necessary.

EMA is accepting feedback on the draft until 30 April.

Reflection Paper

MHRA shares guidance on UK regulation of digital mental health technologies

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published guidance to help developers of digital mental health technologies navigate medical device regulations.

For the past three years, MHRA has worked with the UK National Institute for Health and Care Excellence and other organizations to understand how regulations can facilitate the use of safe and effective digital mental health technologies.

Technologies that qualify as software as a medical device (SaMD) must have UKCA or CE certification to show compliance with the regulations. MHRA will treat technology as SaMD if it has a medical purpose and “sufficient functionality.” The guidance explains how to determine if the technology meets the criteria.

The guidance notes that technologies have a medical purpose “if they are intended as part of the broad process involved in the management of mental ill health,” including because they help assess risk, diagnose or treat mental health conditions. A product that supports treatment of subclinical poor sleep does not have a medical purpose but a device used to treat insomnia would meet the SaMD definition.

The sufficient functionality requirement differentiates between devices that only perform computational tasks, such as data storage, and those with more advanced data processing capabilities. MHRA said devices with the more advanced capabilities are typically classified as SaMD.

Press Release, MHRA Guidance

EMA answers questions about mitigating the risk of diethylene and ethylene glycol

EMA has updated its guidance on good manufacturing and distribution practices to answer questions about glycerol and other excipients at high risk of diethylene and ethylene glycol (DEG/EG) contamination.

The agency added three questions to the guidance last year in response to incidents of contamination in 2022 and 2023 in countries including Gambia and Indonesia. The newly added questions cover what EMA is doing to prevent contamination in the EU and how the actions affect manufacturers and importers.

EMA recommends companies consider glycerol, propylene glycol, and certain macrogols as higher-risk materials when designing supplier assurance and incoming goods control programs. The agency expects manufacturers, especially importers, to “be able to exhibit a good knowledge of the supply chains and apply this knowledge and principles of quality risk management to their programs.”

The document acknowledges the difficulty companies may face when trying to perform the recommended limit test for DEG and EG, which involves a gas chromatographic method, on large numbers of containers. EMA said alternative tests are under consideration, but the existing limit test is still the official method.

The document also covers the implications of worries about DEG and EG for marketing authorization applications. EMA said applicants should provide excipient specifications that ensure the risks are mitigated and discuss and evaluate the mitigation “in the context of the overall control strategy for the finished product.”

EMA Q&A

EFPIA joins call to withdraw artificial intelligence liability directive

Pharma and medtech trade groups have joined with representatives of other industries to push for the withdrawal of the artificial intelligence liability directive.

The European Commission published a proposal for the directive in 2022 “to improve the functioning of the internal market by laying down uniform rules for certain aspects of non-contractual civil liability for damage caused with the involvement of AI systems.” However, 12 organizations from a range of sectors see problems with the proposals.

EFPIA, MedTech Europe and other industry groups said the directive would “add unnecessary legal complexity and uncertainty to an already intricate and novel legal framework impacting AI in Europe.” They also questioned the value the proposal provides given the EU already has frameworks on liability and consumer protection.

The groups said the “proposal would harm EU competitiveness by increasing the regulatory burden, impacting costs and disincentivizing investments in AI innovation.” By withdrawing the plan, EFPIA and its co-signatories believe the EU can drive its regulatory simplification and better regulation agenda while supporting “the development and roll-out of innovative products and services.”

The trade groups want the EU to implement and test the new product liability directive before considering any changes or additional liability frameworks. The directive entered into force late last year, and EU countries have until December 2026 to transpose the requirements into national law.

Joint Letter

Other news:

The Swiss Agency for Therapeutic Products (Swissmedic) and Health Canada have expanded their approach to mutual recognition. The new approach covers the recognition of good manufacturing practice extra-jurisdictional inspection outcomes, plus human blood or human plasma ingredients and products. Reliance processes now include on-site evaluations and pre-approval inspections. Swissmedic Notice

The European Commission’s in vitro diagnostic panel has provided scientific advice on SARS-CoV-2 tests, stating that the virus can still cause serious illness but “no longer poses a life-threatening risk with a significant mortality rate for the general European population.” The Medical Device Coordination Group updated its own COVID-19 advice in light of the reduced risk. Press Release

The Biosimilar Medicinal Products Working Party plans to consider revising the EMA guideline on similar biological medicinal products this year. Changes to the guideline on nonclinical and clinical issues linked to biosimilars that contain biotechnology-derived proteins as an active substance are also on the plan. The working party outlined the activities as part of its work plan for 2025, 2026 and 2027. Work Plan

The EU Clinical Trials Regulation (CTR) has become fully applicable. More than 5,000 trials have moved to the CTR over the past three years, EMA said. The sponsors of studies that were still on the old system after 30 January may face corrective measures and penalties. Press Release

Euro Roundup: EMA seeks feedback on approaches to qualifying novel, non-mutagenic impurities

Related topics

Recommended content

Welcome to the new RAPS Digital Experience