Euro Roundup: EMA seeks feedback on reducing the use of non-human primates in safety testing

The European Medicines Agency (EMA) has released a draft reflection paper on ways to minimize the use of non-human primates (NHP) when testing the safety of human medicines.

A 2010 European Union directive aimed to limit the use of NHPs. EMA’s draft reflection paper reinforces the directive's message. Citing the directive, the limitations of NHP data and alternative ways to evaluate risks to humans, EMA said the use of NHPs in non-clinical safety testing should be a last resort based on a sound justification.

The number of animals used must be limited to the absolute minimum to allow characterization of the risk to clinical trial participants. EMA said existing guidance documents support that objective by providing multiple ways to reduce, refine, or replace, the 3Rs of animal testing, NHPs in safety testing.

Currently, the 3R opportunities presented in the guidance are underutilized, EMA said. The agency is recommending that applicants make full use of the existing guidance documents and consider compiling a weight of evidence (WoE) to justify deviations from general regulatory guidance when needed.

The WoE approach entails using non-animal methods and other available information on a drug candidate to assess the risk of a molecule without running tests in NHPs. EMA listed the role of the pharmacological target and drug specificity data as examples of evidence that can be used to make a WoE case.

Pharmaceutical and assay developers that want to use novel methods that are not yet addressed in regulatory guidance should engage with EMA, the agency said. EMA is urging companies with novel methods to talk to its Innovation Task Force and use its scientific or qualification advice procedures.

Similarly, the agency is encouraging pharma companies that are considering using NHPs for non-clinical safety studies to engage with regulators early in the development process. Engagement should include seeking regulatory alignment, EMA said.

The guidance features advice specific to a range of modalities. EMA said rodent data is generally considered sufficient to evaluate the developmental and reproductive toxicity of small molecules. Developers of biologics should run repeat dose toxicity studies in rodents when suitable species are available.

EMA is accepting feedback on the draft until 31 January.

Draft Paper

EMA shares draft guideline on quality aspects of phage therapies

EMA is seeking feedback on draft guidance intended to clarify regulatory expectations for the quality documentation of bacteriophage active substances and finished products.

Bacteriophages’ potential to kill bacteria that are resistant to antibiotics has fueled interest in the therapeutic use of the viruses in recent years. However, while researchers began studying the approach decades ago, there is a lack of regulatory precedents for developing and making the therapies. Agencies worldwide have responded with regulatory proposals to support the emergence of the sector.

EMA’s draft guideline reflects its classification of phages as biological medicinal products and recognition of how the viruses differ from the rest of the class. While biological guidelines apply to phages, the viruses’ high specificity, self-propagation, potential for evolution, and risk of horizontal gene transfer mean specific advice is also needed, EMA said.

The draft guideline covers regulatory expectations for the development, manufacture, characterization, and control of phages. EMA has proposed that companies sequence the entire bacterial genome and plasmids in their master cell banks. The characterization should include an analysis of genes encoding for potential detrimental factors such as antibiotic resistance determinants and toxins.

EMA also expects companies to evaluate the capacity of a phage to transfer detrimental factors to the bacteria in a patient. Some phages can package bacterial DNA alongside their own DNA and transfer it to a receiving cell. Random packaging of host DNA can occur in a process called generalized transduction. EMA wants companies to address the capacity of phages to mediate that process in their applications.

Phages are also subject to the requirements that apply to all biological medicines. That could constrain phage developers. The ability to adapt multi-phage formulations to changing bacterial pathogens is one potential benefit of the modality. However, the EU biological medicine framework does not address products with a flexible composition.

Under the biological framework, companies must file a marketing authorization extension to change the composition of an authorized product. EMA could require clinical data showing that the safety and efficacy of a replacement phage active substance are not significantly different from the previous one.

Changing the composition is outside the scope of the draft, but EMA used the document to offer high-level advice. Requests for marketing authorization extension will be assessed on a case-by-case basis and in light of the specific requirements for phages, the agency said. EMA is advising applicants to seek scientific advice to address the specific concerns and regulatory pathways for their products.

EMA is seeking feedback on the draft until 30 April.

Draft Guideline

MedTech Europe backs creation of CGM standard harmonized against medtech regulations

MedTech Europe has backed the creation of an internationally recognized standard for continuous glucose monitoring (CGM) technologies.

The trade group outlined its views in a position paper. MedTech Europe welcomed the International Standardisation Organisation’s (ISO) development of a standard that is harmonized against the European Union medtech regulations and called for industry and other groups to engage in the process. That call reflects a belief the full range of views is needed to ensure standards are practical and implementable.

MedTech Europe shared its view on the process, calling for all diabetes standards to follow four key principles. One principle covers alignment with existing regulatory frameworks and processes. The trade group wants standards to complement, rather than duplicate or conflict with, existing EU regulations.

Another principle covers MedTech Europe’s desire to avoid unnecessary barriers that could limit access to technologies. The trade group said any additional standards should set “meaningful benchmarks that support device performance and reliability without imposing overly prescriptive or narrowly defined technical criteria.” MedTech Europe wants the EU to adapt to ISO standards to minimize burdens.

“Any proposed EU-specific quality standards should be future-proofed to ensure that, in the event they are either superseded by or used in conjunction with future internationally approved standards ..., manufacturers do not face duplicative requirements that could slow innovation and limit access,” the trade group said.

Position Paper

EMA seeks feedback on molecule-independent device bridging approach

EMA is holding a consultation into its draft qualification opinion for a molecule-independent device bridging approach (MIDBA).

The approach is designed to simplify clinical bridging from a manual subcutaneous injection via a syringe to an autoinjector. Specifically, MIDBA could eliminate the need to generate molecule-specific pharmacokinetic comparability assessments for new monoclonal antibodies for device bridging when switching to Ypsomed’s YpsoMate autoinjector.

EMA is considering allowing the use of MIDBA under certain conditions. Companies would need to provide a justification confirming that the specified conditions have been met in regulatory submissions to EMA.

The agency is seeking feedback on its draft opinion until 19 December.

Draft Opinion

Other News:

ABPI and the UK government have agreed to give companies another two weeks to decide whether to leave the 2024 voluntary scheme for branded medicines pricing, access and growth. The second delay pushes the deadline to November 14. ABPI Notice

EFPIA director general Nathalie Moll has said swift EU reforms could make 2026 a turning point for clinical trials in the region. Cautious optimism is in the air, Moll said, and proposed reforms such as the EU Biotech Act present opportunities to maintain the momentum. Blog Post

Euro Roundup: EMA seeks feedback on reducing the use of non-human primates in safety testing

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