Key Takeaways
- The European Medicines Agency’s innovation network says regulatory changes are needed to give clarity to sponsors on when they can use alternatives to animal testing, known as new approach methodologies (NAMs).
- NAMs intended for regulatory use in medicine development are currently advancing to technology readiness levels sufficient for initial engagement with regulatory authorities and inclusion in weight-of-evidence regulatory submissions and/or in specific contexts of use.
- In a horizon scanning report, the innovation network said that large pharmaceutical companies are less likely to share data on NAMs with regulators than SMEs and academia.
- Regulators must adopt strategies that encourage developers to share data on NAMS, for instance by better communicating existing ways that companies can seek advice on the use of NAMs.
The EU innovation network (EU-IN), which regulators set up to improve regulatory support for drugmakers, says that companies need clearer information around when and how they can use new approach methodologies (NAMs) for reducing or replacing animal studies during drug development.
NAMs refer to methods of testing medicines that are compliant with the 3Rs principles involving the use of animals in research – replace, reduce or refine.
The EU-IN, which was set up by the European Medicines Agency and EU Heads of Medicines Agencies, notes that NAM techniques themselves are not necessarily new, but their application to the regulatory decision-making process is.
“NAMs intended for regulatory use in medicine development are currently advancing to technology readiness levels sufficient for initial engagement with regulatory authorities and inclusion in weight-of-evidence regulatory submissions and/or in specific contexts of use,” the EU-IN said.
The network has published a horizon scanning report that looked at trends in the use of NAMs between 2009 and 2024, and which makes key recommendations for the European medicines regulatory network (EMRN) to consider.
The report was issued shortly ahead of a similar announcement from the US Food and Drug Administration’s newly installed commissioner, Martin Makary. On 10 April, Makary said that the inclusion of NAM data would be encouraged for investigational new drug (IND) products and that the agency would begin to use pre-existing real-world safety data from other countries with similar regulatory standards in its reviews as part of its own push to make animal testing the exception, rather than the norm.
The EU-IN was set up to strengthen the collaboration between national competent authorities (NCAs) and the EMA on regulatory matters relating to emerging therapies. This means that the horizon scanning report could lead to changes in the EU regulatory framework that will benefit industry.
The network also highlighted industry’s move towards “more efficient and innovative approaches in medicine development,” such as platform approaches, as well as “increased political and societal concerns on the use of animals” as reasons for greater support for NAMs.
It said that the EMRN – which includes the EMA, the European Commission and NCA in the European Economic Area – should develop a “clear framework for NAM qualification.”
This framework should include “a clear definition of a context of use, what is expected in terms of comparison to existing gold standards and highlight the importance of translational, clinically relevant endpoints.”
The EU-IN also called for increased clarity on the definition of validation and qualification of NAMs and the expected requirements, and said this should be harmonized internationally where possible.
In addition, it recommended that the EMRN engages with developers and other stakeholders on the use of NAMs and said the EMRN should advocate for “regulatory flexibility” within the network to allow for the successful integration of NAMs.
Big Pharma Needs To Share More Data
Another challenge highlighted in the horizon scanning report was a lack of communication and data sharing between stakeholders and regulatory agencies, particularly from large pharmaceutical companies.
The EU-IN said that much expertise on NAMs “has been developed in-house within industry” and that “large enterprises with large portfolios have pioneered NAMs for internal de-risking strategies in early-stage medicine discovery and development.”
Large companies, it said, “tend to share NAM data with regulators on a more need-to-know, case-by-case basis to support weight-of-evidence approaches, particularly for toxicological assessments.”
An EMA database analysis of regulator-developer interactions found that most requests for regulatory discussions on NAM innovation are made by small and medium enterprises (SMEs), academia and EU-funded consortia, the EU-IN report said.
However, part of the reason why pharmaceutical companies have been reluctant to share NAM information with regulators relates to concerns that this will lead to a negative decision for their regulatory applications, the EU-IN explained.
“Strategies to encourage NAM developers and end-users, including large enterprises, to share their data with regulators should be adopted,” the group recommended.
It said that this could be done by better communicating various options for advice mechanisms and platforms for information sharing at the national and EU levels, and that clarity should be provided on when companies should contact regulators.
Regulators should also provide clarity on how data on NAMs is being used, the report said.
EMA Push Towards 3Rs
The horizon scanning report is part of an increased effort from the EMA and other EU authorities towards encouraging the use of NAMs and providing clarity for companies on when such tests are acceptable from a regulatory perspective.
Earlier this month, the chair of the EMA’s 3Rs working party (3RsWP) asked industry to review an EMA reflection paper that lists various tests used in drug development alongside existing and newly-identified areas where NAMs could be used instead.
Meanwhile the European Pharmacopoeia Commission said in February that it was removing general chapters on pyrogens, histamine and depressor substances from the European Pharmacopoeia (Ph. Eur). These involve testing on rabbits, guinea pigs and cats.
