Integrating New Approach Methodologies (NAMs) to advance biomedical research and regulatory testing

The protection of European communication networks has been identified as an important security interest of the Union and its Member States. For further details, you are advised to refer to the introduction of the destination under which this topic falls (as found in the Health Cluster work programme part for 2026-27).

For “biomedical applications”, the call text refers to “platforms that 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 “regulatory testing”, the call text refers to “the safety assessment of chemicals, other medicinal products and medical devices”. The call text further clarifies that regulatory testing relates to “medicinal products and medical devices, and/or industrial and environmental chemicals”. In addition, for regulatory testing, “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.” Based on these clarifications, applicants and evaluators would be able to assess whether activities related to chemical safety, hazard characterisation, risk assessment, and drug safety fall within the scope of the topic.

Yes, this is a Lump Sum topic, as stipulated in the specific conditions of the topic. To define and justify the Lump Sum, you need to provide a detailed budget table with cost estimations (downloadable as an Excel file form the online submission system). The estimations must be an approximation of your actual costs and meet the eligibility criteria of Horizon Europe.

In order to facilitate the evaluation of your proposal, you are encouraged to use the comments part of the detailed budget table and provide any details / explanations that are needed to better understand the specificities of your proposal. You are also advised to systematically justify any deviations in personnel costs.

Moreover, if your lump sum budget contains any cost items in cost category C and/or D, please make sure to justify these items in the comments part of the detailed budget table, as the proposal template has been simplified by removing this information from Part B and bringing it closer to the relevant budget items. Specifically, you must include justifications in the comments part of the detailed budget table if you are in any of the following situations:

• If the sum of the costs for ’travel and subsistence’, ‘equipment’, and ‘other goods, works and services’ (i.e. the purchase costs) exceeds 15% of the personnel costs for a participant. If this is the case, justify the most expensive cost item(s) up to the level that the remaining costs are below 15% of personnel costs.
• If other cost categories (e.g. internally invoiced goods and services) are used.
• If in-kind contributions are used (non-financial resources made available free of charge by third parties, which must be included as direct costs in the corresponding cost category, e.g. personnel costs or purchase costs for equipment).

Please note that the definition of clinical studies, together with additional useful information can be found in the introduction of Health Cluster Work Programme part for 2026-2027.

Additionally, we would like to bring to your attention the fact that the World Health Organization (WHO) has published a “Guidance for best practices for clinical trials”. You are not required not follow this guidance, however we encourage you to do so.

Finally, we would also like to encourage you to consider the latest innovations and advances in the clinical trial design and research methods in order to evaluate promising interventions allowing shorter development timings.

As indicated in the call text, the JRC should collaborate with any successful proposal after the proposal’s approval.

If the comparison between patients’ tissues and hiPSC-derived 3D tissue models involves the systematic prospective or retrospective collection and analysis of health data from patients or healthy individuals, it may fall under the definition of a clinical study. In such cases, applicants should provide the relevant information using the clinical study template. However, where the work relies exclusively on fully anonymised biobank samples with no associated health data, or does not constitute a clinical study as defined in the document “INFORMATION ON CLINICAL STUDIES” available on https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/topic-details/HORIZON-HLTH-2026-01-TOOL-03, the submission of a clinical study template is not required.

Embedded sensors refer to sensing elements that are integrated within, or directly incorporated into, the experimental platform, enabling in situ and/or real-time monitoring of physiological responses.

The call text defines NAMs broadly and explicitly includes human ex vivo assays among the range of NAMs that fall within the overall scope of the topic. At the same time, the call further specifies that proposals should develop or optimise scalable and reproducible platforms based on one or more of the listed categories, namely advanced in vitro assays, iPSC-based/organoid/OoC systems, and human tissue-based platforms. In this context, proposals are expected to anchor their platform development or optimisation within one or more of these specified categories. Approaches relying on ex vivo methods may therefore be considered in scope where they can be clearly positioned within these categories.

It is not mandatory to develop predictive models or full digital twin systems. AI approaches that analyse complex biomedical data and extract meaningful features, patterns, or mechanistic insights can be fully within scope, if those features are demonstrably linked to predicting outcomes of biomedical interventions or risk/safety assessment, or form a justified and validated component of such predictive capability.

A proposal may still be well aligned with the central objectives of topic HORIZON-HLTH-2026-01-TOOL-03, even if the expected direct reduction in animal use is limited, provided that it convincingly contributes to several of the expected outcomes of the topic, as indicated in the call. Proposals addressing biomedical applications where no relevant animal models are available may still be in line with the objectives of the call if the proposed NAMs enhance disease-modelling precision.

No. It is not mandatory to address both use cases. Proposals may focus on either: use of NAMs for biomedical research, or use of NAMs for regulatory/safety assessment, or both, if scientifically justified and feasible.

Validating a NAM for a specific class of new molecules is within scope provided the Context of Use (CoU) is well defined and justified, and with validation strategy linked to that CoU. The use of molecules under development can therefore be appropriate when necessary to demonstrate the performance of the NAM within the defined CoU. However, the centre of gravity must remain the validation of the NAM for its intended use, not the development of a specific therapeutic product.

Ethical aspects are important, as projects may involve human biological materials, health data, advanced in-vitro models, AI/computational tools, or potential regulatory use of NAMs. Proposals must therefore demonstrate that ethical requirements are properly anticipated and managed. A dedicated Work Package (WP) on ethics is not mandatory but may be appropriate in projects with significant ethical complexity.

Clinical studies are not the primary focus, but they may play a supporting and enabling role where this is clearly justified and necessary for the development, qualification, or validation of the NAMs.

Yes, this can be within scope. However, the primary objective is the development, optimisation and validation of human-relevant New Approach Methodologies (NAMs). Comparison with existing approaches, including animal models, may therefore be appropriate as a benchmarking or validation element, provided it is well-justified, proportionate, and NAM-driven.

This means that NAMs should be able, within a clearly defined and feasible scope, to capture biologically relevant sources of human variability that influence the disease or application being studied, rather than representing only an “average” or single model. For a given disease/application, this does not require modelling the full diversity of the population, but rather demonstrating that NAMs can reflect key variability factors that are known to affect outcomes, mechanisms, or safety.

The call text specifies that proposals should develop or optimise scalable and reproducible platforms based on one or more of the following three NAM categories: advanced in-vitro assays; iPSC-based models, organoid or complex Organ-on-Chip (OoC) systems derived from patients and/or healthy donors; human tissues that closely replicate physiological and pathological conditions. The call further explicitly allows proposals to incorporate one or both of the following complementary approaches to enhance predictive power and clinical or regulatory relevance: – AI-driven predictive modelling trained on high-quality, curated, bias-minimised datasets; and/or – virtual twin technologies to simulate disease progression, responses to interventions, or to support clinical trial optimisation. In addition, other NAM components may be included, provided they are clearly integrated with and support the core NAM platforms specified in the call, and contribute to improved performance, scalability, or regulatory relevance.

The use of lower organisms (e.g. C. elegans, zebrafish, Drosophila) is not in itself within the primary scope of the topic, as these models do not constitute human-based NAM platforms. However, such models may be used only as supporting or comparative tools, for example for mechanistic exploration, hypothesis generation, or benchmarking, provided they are clearly justified and do not constitute the main focus of the proposal, and that the core objectives remain centred on the development or optimisation of human-relevant NAM platforms as specified in the call.

The call text foresees the involvement of multiple stakeholder groups, including regulators, while recognising that the degree and nature of their involvement may vary depending on the primary focus of the proposal. In proposals primarily targeting biomedical applications rather than regulatory use, a more limited involvement of regulators may therefore be appropriate, provided that the consortium composition and stakeholder engagement are adequately justified in relation to the call text, the project objectives, and the intended use of the developed or improved NAMs.

The Health Cluster Work Programme part for 2026-2027 includes a “right to object” condition for nearly all topics, giving the granting authority the right to object to a transfer of ownership or to the exclusive licensing of results, up to 4 years after the end of the action.

For applicants and beneficiaries, little is expected to change, as in previous years this condition had been part of the General Annexes, having legal force across all parts of Horizon Europe (including the Health Cluster topics). In practise, the granting authority may invoke the “right to object” under specific conditions, which so far has happened in very rare occasions over the many years of Horizon Europe.

More details below from Annex 5 of the General Model Grant Agreement:

Where the call conditions in Horizon Europe actions provide for the right to object to transfers or licensing, the granting authority may — up to four years after the end of the action — object to a transfer of ownership or the exclusive licensing of results, if:

the beneficiaries which generated the results have received funding under the grant

it is to a legal entity established in a non-EU country not associated with Horizon Europe, and

the granting authority considers that the transfer or licence is not in line with EU interests.

Beneficiaries that intend to transfer ownership or grant an exclusive licence must formally notify the granting authority before the intended transfer or licensing takes place and:

identify the specific results concerned

describe in detail the new owner or licensee and the planned or potential exploitation of the results, and

include a reasoned assessment of the likely impact of the transfer or licence on EU interests, in particular regarding competitiveness as well as consistency with ethical principles and security considerations.

The granting authority may request additional information.

If the granting authority decides to object to a transfer or exclusive licence, it must formally notify the beneficiary concerned within 60 days of receiving notification (or any additional information it has requested).

No transfer or licensing may take place in the following cases:

pending the granting authority decision, within the period set out above

if the granting authority objects

until the conditions are complied with, if the granting authority objection comes with conditions.

A beneficiary may formally notify a request to waive the right to object regarding intended transfers or grants to a specifically identified third party, if measures safeguarding EU interests are in place. If the granting authority agrees, it will formally notify the beneficiary concerned within 60 days of receiving notification (or any additional information requested).