This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination “Developing and using new tools, technologies and digital solutions for a healthy society”. To that end, proposals under this topic should aim to deliver results that are directed at, tailored towards and contributing to several of the following expected outcomes:

• Researchers are in possession of improved human-relevant New Approach Methodologies (NAMs) platforms that capture the genetic, phenotypic, age-related, immune, microbiome, and environmental exposure variability of the human population. These innovations support more equitable healthcare solutions and personalised treatment strategies across diverse life stages.
• Industry gets access to platforms that allow a faster pace of innovation for the development of more cost-effective targeted therapeutic interventions and improvement of the safety assessment of chemicals, other medicinal products, and medical devices.
• Patients benefit from innovative platforms and strategies that improve prediction, prevention and treatment of diseases, in particular through enhanced understanding of disease pathways and mechanisms.
• The general population is better protected through a safer environment, as these platforms enhance the detection and mitigation of risks posed by chemicals and other potentially harmful substances.
• Regulatory bodies gain confidence and trust in NAMs, supporting their integration into product development, risk assessment, and approval processes.
• Fewer live animals are used in biomedical research and regulatory testing.

Scope:

This topic aims to support the ongoing paradigm shift in biomedical research and safety assessment of chemical compounds by fully integrating NAMs across the entire research and regulatory spectrum, from basic discovery phase to clinical application, and regulatory testing of medicinal products and medical devices, and/or industrial and environmental chemicals.

NAMs include a wide range of innovative and human-relevant technologies such as in-vitro or human ex-vivo assays, organoids, Organ-on-Chip (OoC) systems, human tissue models, induced Pluripotent Stem Cell (iPSC) applications, virtual twin tools, in-silico methods, and Artificial Intelligence (AI)-driven modelling.

Although the Commission and several Member States have supported the development of NAMs for over two decades, primarily in the context of chemical risk assessment, regulatory uptake remains limited. There is a need to address this situation by delivering validated NAMs solutions that can be adopted by industry and accepted by the regulators for the safety assessment of chemicals. In parallel, there is a growing readiness to expand the development and application of NAMs across the entire biomedical research spectrum, from early discovery through to clinical translation and regulatory testing of medicinal products and medical devices.

Proposals should bring together stakeholders from academia, health-related infrastructures, SMEs^[1], industry, and regulators to develop new NAMs platforms or improve existing ones that could be used for biomedical applications and/or regulatory testing. For biomedical applications, these platforms should enhance disease modelling precision, especially in areas where current animal models are of limited human relevance, and where NAMs could effectively complement or replace animal studies. For proposals addressing regulatory use, in particular the safety assessment of chemicals, other medicinal products and medical devices, the intended context(s) of use should be clearly defined, with validation strategies and methodologies aligned with current OECD and/or European Medicines Agency (EMA) guidance. Early, proactive, and sustained engagement with regulators should also be demonstrated.

Proposals should develop or optimise scalable and reproducible platforms based on one or more of the following:

• Advanced in-vitro assays.
• iPSC-based models, organoid or complex OoC systems derived from patients and/or healthy donors.
• Human tissues that closely replicate physiological and pathological conditions.

In order to enable real-time monitoring of physiological responses, proposals should consider integration of embedded sensors. They should also address biological diversity, reflecting variations in genetics, phenotype, age, immune status, and microbiome across the population.

Moreover, proposals may incorporate one or both of the following complementary approaches to enhance predictive power and clinical relevance:

• AI-driven predictive modelling trained on high-quality, curated, bias-minimised datasets to predict outcomes of biomedical interventions, or risk assessment.
• Virtual twin technology to simulate disease progression, responses to interventions, and support the optimisation of clinical trials.

To maximise scientific impact, interoperability, and reuse, all data generated should comply with FAIR^[2] principles. Proposals should describe how data will be curated, standardised, and shared within or linked to the European Health Data Space (EHDS)^[3] or other repositories, and/or relevant ESFRI^[4] research infrastructures.

In order to optimise synergies and increase the impact of the projects, all proposals selected for funding from this topic will form a cluster and be required to participate in common networking and joint activities.

Proposals should consider involving the European Commission's Joint Research Centre (JRC), including its EU Reference Laboratory for alternatives to animal testing (EURL ECVAM)^[5], to take advantage of its expertise and relevant activities in bridging research and application communities and facilitating uptake of NAMs in biomedical research and regulatory testing. In that respect, the JRC should collaborate with any successful proposal and this collaboration should be established after the proposal’s approval.

Applicants envisaging to include clinical studies^[6] should provide details of their clinical studies in the dedicated annex using the template provided in the submission system.

[1] https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32003H0361

[2] See definition of FAIR data in the introduction to this Work Programme part.

[3] https://health.ec.europa.eu/ehealth-digital-health-and-care/european-health-data-space-regulation-ehds_en

[4] The catalogue of European Strategy Forum on Research Infrastructures (ESFRI) research infrastructures portfolio can be browsed on the ESFRI website: https://ri-portfolio.esfri.eu

[5] https://joint-research-centre.ec.europa.eu/projects-and-activities/reference-and-measurement/european-union-reference-laboratories/eu-reference-laboratory-alternatives-animal-testing-eurl-ecvam_en

[6] Please note that the definition of clinical studies (see introduction to this Work Programme part) is broad and it is recommended that you review it thoroughly before submitting your application.