The work supported under this topic seeks to pursue the aims of Directive 2010/63/EU¹ on the protection of animals used for scientific purposes. It also contributes to the implementation of the 3Rs principles to “replace, reduce and refine the use of animals”, and ultimately helps progress towards no use of animals or animal-sourced materials in research, innovation and development, which is an expectation of society.

The following impacts are expected.

• Break down silos between technological areas and disciplines, and bring together different stakeholders (e.g. health industry, academia, small and medium-sized enterprises (SMEs), patients, regulators, non‑governmental organisations (NGOs) and policy makers) to foster the use of new approach methodologies² (NAMs) and other non-animal approaches in the efficient development, testing and production of safe and effective innovative health technologies³ (e.g. medicinal products, medical devices, biopharmaceuticals, vaccines, in vitro diagnostics) and their combinations.
• Improve public health as patients will benefit faster from safe and effective health technologies developed using NAMs and other non-animal approaches that, where relevant, provide more human-relevant data and are more predictive than current approaches.
• Foster the development of health policies and standards on the use of NAMs and other non-animal approaches in health technologies which will positively affect public health.
• Enhance the competitiveness of the European health industry that will benefit from high quality innovative approaches and methodologies for the development and production of new health technologies, which can reduce the time and costs of processes while significantly reducing the use of animals or animal-sourced biomaterials.
• Help to make the EU more sustainable/autonomous by achieving regulatory validation and uptake of NAMs and other non-animal approaches for the development, testing and production of health technologies that are not dependent on shortages/issues with animal supply.

_{1 DIRECTIVE 2010/63/EU OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 22 September 2010 on the protection of animals used for scientific purposes (OJ L 276, 20.10.2010, p. 33) https://eur-lex.europa.eu/eli/dir/2010/63/2019-06-26.}

_{2 New approach methodologies, as defined in https://www.frontiersin.org/articles/10.3389/ftox.2022.964553/full}

_{3 Heath technology, as defined in the IHI Strategic Research and Innovation Agenda, means a medicinal product, a medical device, or medical and surgical procedures, as well as measures for disease prevention, diagnosis or treatment used in healthcare.}

• Research and innovation (R&I) actions (projects) to be supported under this topic must contribute to all the following outcomes.
• Researchers will benefit from the implementation of NAMs and other innovative non-animal approaches which have been assessed and validated for their performance and found to be relevant, reproducible, predictive, and standardised, ultimately leading, as relevant, to their regulatory acceptance for use in infectious and/or non-communicable disease applications. The new approaches should lead to an improvement in the assessment of health technologies (and animal to human translation where relevant) and/or production processes, and to a significant reduction in the number of animals used. In addition, these approaches may answer questions that current methods cannot, and improve the predictability and robustness of evidence generated for regulatory decision-making.
• European industry will benefit from the establishment and availability of NAMs and other innovative non‑animal approaches for the testing, development and/or production of health technologies that are fit-for-purpose to support regulatory decision making.
• Researchers and developers of innovative healthcare solutions will have access to high-quality data, new recommendations and best practices to incentivise the use of NAMs and other non-animal approaches and their integration in industrial processes. This should be supported by an appropriate digital repository to ensure both the sustainability and scalability of the knowledge base.
• Regulators and policy makers will gain knowledge and have access to high-quality data on the characteristics and use of NAMs and other innovative non-animal approaches in the production and development of health technologies to foster the development of harmonised guidance and requirements, as well as uptake or translation into health policies.

Animals and animal-derived materials are widely used in biomedical research and in the production and development of health technologies. This raises serious ethical concerns, and there is growing societal pressure to move towards alternative approaches and methods. Besides major ethical concerns, there is also scientific evidence that supports moving away from animal-based approaches and finding more human‑relevant methods and strategies for both the assessment of safety and efficacy of new health technologies and for manufacturing. Animal testing requires time-consuming protocols, high costs for animal supply, and the results are not always reproducible and applicable to humans. In addition, for the development and production of health technologies (e.g. in vitro diagnostics) as well as in biomedical research in general, materials of animal origin are required (e.g. biomolecules, sera). These animal-derived products require large amounts of animals for their production. Therefore, also in this context, there is a need to foster progress towards new alternatives (e.g. synthetic matrix, recombinant proteins, optimisation of production processes via artificial intelligence) to reduce the overall number of animals that are bred for these purposes.

NAMs and other innovative non-animal approaches have high potential to improve the development and/or production of health technologies, while contributing to the reduction and replacement of the use of animals. Recent improved biological knowledge, technological advances, computer simulations and innovative non‑animal approaches and methods (e.g. organoids, complex 3D cell models, microphysiological systems¹, in silico models, non-animal derived antibodies and other biomolecules² provide the opportunity to move forward with safer and more effective tools for protecting human health and preventing/treating diseases that would in parallel entail an improvement of animal to human translation or better production processes, as well as helping progress towards the replacement of animals used in biomedical research in general.

While the potential for using non-animal approaches for the production, development and testing of new health technologies is enormous, more evidence and high-quality data for their performance evaluation in comparison with established animal-based approaches for a specific application (such as a production process, primary pharmacology, or next-generation-risk-assessment – NGRA) and for their validation are required by the industry and regulators to implement these alternative approaches in R&D and decision‑making processes. In addition, policy makers require a large body of up-to-date, high-quality knowledge to inform relevant health policies and ensure the long-term goal of full transition to non-animal approaches.

The current topic seeks to address these challenges by exploiting the latest relevant scientific advancements to develop NAMs and other non-animal approaches, which could be more readily available and more efficient than those involving animals, and which should improve either the development, including efficacy and safety assessment, of new health technologies for infectious/non-communicable diseases or the production processes of such technologies.

The projects funded under this topic should aim to do the following.

• Develop new NAM/s or other non-animal approach/es (or a combination of those) or use existing ones in an innovative way to improve (early-stage) assessment of new health technologies (and animal to human translation where relevant), or to improve the production processes of health technologies (such as bio/pharmaceuticals, vaccines, medical devices including in vitro diagnostics, and radio-chemicals).
• Specify the context of use (e.g. primary pharmacology, toxicology, safety, quality control, production processes) of the novel approach/es, how it/they can be integrated efficiently in the relevant workflows and propose and implement a plan to carry out their performance evaluation and validation, as well as demonstrate their added value in comparison to relevant established animal-based approaches.
• Make a comparative evaluation of the different approaches to replace, reduce and refine animal use, including the identification and assessment of parameters that influence their usefulness such as their reliability, reproducibility, robustness and fitness for purpose.
• Generate evidence on the robustness, reliability, and applicability of these novel approaches in an industrial research and development (R&D) context and to support regulatory decision making in testing, development or production of health technologies, as relevant. Accordingly, applicants should develop a strategy/plan for generating appropriate evidence to support regulatory acceptance and engage with regulators in a timely manner (e.g. through the European Medicines Agency [EMA] Innovation Task Force or qualification advice).
• Gather and produce high quality datasets to generate a solid knowledge base for supporting the use of NAMs and other non-animal approaches in the field of health technology and drive 3Rs implementation. To ensure the sustainability of the results and foster future development and validation of innovative non‑animal approaches, applicants should develop a fit-for-purpose scalable digital data repository. Applicants should consider and leverage as much as possible existing infrastructures.
• Establish a collaboration platform between all relevant stakeholders from public and private sides, including regulatory agencies and policy makers, to exchange information, prepare white papers and guidelines to foster uptake or translation into health policies, supporting an adequately reflected transition to full implementation of non-animal approaches in health technology development and manufacturing. Patients and/or patient organisations may be included and actively contribute to such activities by providing, for example, their insight on the use of human-derived samples, as relevant.
• Accelerate the broad implementation of the NAMs and other non-animal approaches in research through a strong communication and dissemination plan, fostering also exchanges and cross fertilisation with other projects funded in this area.

Projects funded under this topic are expected to contribute to relevant EU health policy initiatives such as the new Industrial Strategy for Europe, the European Health Emergency and Response Authority (HERA) and the EC proposal on the European Health Data Space (EHDS).

Furthermore, applicants are expected to explore and/or implement synergies³ and complementarities with relevant initiatives/projects, at national, European and international level. They should also consider, as relevant, the activities of the 3Rs Working Party of EMA⁴.

^{1 Microphysiological Systems: Stakeholder Challenges to Adoption in Drug Development - PMC (nih.gov)}

^{2 EURL ECVAM Recommendation on Non-Animal-Derived Antibodies}

^{3 Examples of synergies at European level (not exhaustive list): RISK-HUNT3R RISK, Precision Tox, ONTOX, projects that will be generated from HORIZON-HLTH-2024-TOOL-05-06-two-stage topic, HORIZON-HLTH-2024-IND-06-09}

^{4 3Rs Working Party (3RsWP) plenary meeting - Public session on the 2023 work plan}