Translating Disruptive New Approach Methodologies (NAMs) Into Practice

This Challenge supports ambitions to maintain and strengthen the health sector in Europe. It will:

• Accelerate the development and validation of disruptive NAMs for biomedical applications, including medicinal products and medical technologies
• Support regulatory innovation by providing evidence-based recommendations for the assessment of safety, efficacy, and quality of human health products using NAMs.
• Enable citizens to benefit from novel technologies that have been assessed through rigorous NAMs that have been validated to can predict potential effects in humans, and
• Provide industry with a harmonised and standardised NAM-based assessment toolkit that is faster and more flexible.

Specific Objectives

This is a two-stage Challenge competition with the ultimate ambition to deliver robust, validated NAMs that constitute a representative model or prototype system i.e. achieve TRL 6 after Stage 2. Applicants should apply to Stage 1 only where there is an outlook of the potential impact in the longer term.

Stage 1 – Solution validation and benchmarking

Applicants should:

• Take forward preliminary engagement with regulatory authorities, notified bodies and industry stakeholders
• Map regulatory, clinical, standardisation (where applicable) and industrial needs, and use this to develop a roadmap for adoption
• Develop a methodology for performance assessment
• Deliver small-scale feasibility experiments or modelling
• Conduct initial performance benchmarking (human relevance, reproducibility, transferability of the approach)
• Assess ethical, data governance and scalability considerations, as applicable to the given NAM under development.

The following milestones need to be achieved at the end of Stage 1:

• Evidence that the NAM is viable for human relevant biomedical innovation, and addresses the needs of the identified use cases, and
• Clear commitment from industrial end-users and a well-defined regulatory plan to further develop the NAM in Stage 2.

Progress to Stage 2 will be contingent on delivering a full proposal which will be assessed alongside the milestones achieved under Stage 1.

Stage 2 – Development and user testing

Applicants selected for Stage 2 will further develop and validate a functional, scalable NAM prototype ready for regulatory, industrial, or clinical uptake. Activities must cover a number of the following elements:

• Benchmarking the NAMs against state-of-the-art animal models and/or human trials
• Demonstration in relevant application, such as disease modelling, or testing of medicinal products and medical technologies for safety, efficacy, or quality
• Organisation of consultation meetings/workshops with industrial end users, regulators, CROs (Contract Research Organisations), standard setting bodies or other relevant stakeholders to gather further needs and feedback
• Engagement with infrastructures for testing and data collection as testing and validation of the NAM outside the developer’s lab
• Development of regulatory-grade data packages suitable for submission to relevant agencies (e.g. EMA, FDA, OECD), and
• Documentation on scalability, standardisation, and potential barriers to uptake.

During the project’s implementation phase, beneficiaries will be encouraged to consider using the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) of the European Commission’s Joint Research Centre for aspects of standardisation, automation and validation of in vitro methods. These facilities operate and provide support at the interface between pre-normative research, regulatory sciences and innovation.

New Approach Methodologies (NAMs) have the potential to replace, reduce or refine animal use in the testing96 of medicinal products. Scientific progress in recent decades has delivered several animal-free NAMs that have the potential to transform how we understand human biology and assess the safety, efficacy, and quality testing in the health sector. However, a lack of knowledge, experience and confidence in the use of such novel methodologies has limited their adoption by end users, including, for example, industry and regulators.

This Challenge competition therefore looks to accelerate the adoption of NAMs in biomedicine and support companies that want to bring NAMs to the market. Applicants should propose innovative and disruptive NAMs addressing one or both of the following areas:

• Preclinical biomedical research
• Testing of medicinal products and medical technologies for safety, efficacy, or quality.

Human organoids or microphysiological systems (e.g. organ-on-chip, disease-on-chip), in chemico methods, digital twins, virtual patient simulations, AI-enhanced predictive models, mechanistic or integrated in silico platforms, 3D- advanced human tissue model are in scope.

Applicants to this Challenge call should already have:

• Proven the viability of their proposed solution in a lab environment at TRL 4 (lab or in silico);
• Have letters of intent of at least one of the following stakeholders: an industrial end-user or regulatory body interested in the proposed project; and
• Have access to an appropriate infrastructure to carry out the planned activities in Stage 1 and 2.