Case studies for the effective use of NAMS for the assessment of chemicals and pharmaceuticals
Objectives
WP4 aims to build confidence in the use of NAMs to demonstrate their applicability through targeted case studies. Its main objective is to generate evidence and frameworks needed to support a transition away from traditional animal-based testing towards NAM-driven safety and efficacy assessment of chemicals and pharmaceuticals.
By designing and implementing selected case studies, WP4 will help bridge the gap between methodological innovation and regulatory application. It will translate complex NAM data into clear assessment principles and actionable recommendations for regulators, industry, and academia. Specifically, WP4 will:
Design a conceptual model for NAM-based case studies that can be applied across different regulatory contexts.
Implement four types of case studies, covering hazard identification, Point of Departure (PoD) derivation, Next Generation Risk Assessment (NGRA) and pharmaceutical safety/efficacy evaluation.
Extract assessment principles from case studies outcomes, translating them into practical frameworks and recommendations for regulators and risk assessors.
Refine findings through multi-actor dialogue with regulators, industry, and academia to ensure the resulting case studies and recommendations are robust and relevant.
Through these activities, WP4 will deliver practical examples that illustrate how NAMSs can be integrated into regulatory decision-making for environmental and human health safety assessments. A key element for the NAMWISE case studies is the focus on using information that is already available, suggesting its role in regulatory assessments within the current and future frameworks.
Meet the work package leader
Key activities
Work Package 4 is structured into five core tasks, transitioning from the design of case studies to the creation of actionable regulatory-ready guidance.
The work is structured into four core tasks:
Task 4.1 –
Design of NAM-based case studies
Develops the conceptual model and selects a short-list of case studies addressing key regulatory questions in both chemical and pharmaceutical domains. It will focus on data-rich substances and contexts of use that are relevant across EU regulatory frameworks. Four case-study types are planned:
- Hazard identification for Classification and Labelling (C&L)
- Hazard characterization based on PoD derivation
- NGRA-based safety assessments for chemicals and pharmaceuticals
- Safety and efficacy assessments for pharmaceuticals
Task 4.2 –
Implementation of case studies
Constitutes the core activity of WP4. Implements all case studies in parallel integrating NAM-based evidence and, where relevant, combining it with selected animal data, to construct hazard and risk assessments.
Task 4.3 –
Dialogue and consultation with stakeholders
Organizes a dedicated workshop with experts from regulatory agencies, industry, academia and other stakeholders to gather feedback on the case studies and discuss general assessment principles.
Task 4.4 –
Reporting and critical analysis of case studies
by the consortium using a predefined reporting template to examine the consistency and robustness of NAM-based conclusions as well as uncertainties and data gaps.
Task 4.5 –
Recommendations & assessment frameworks
Synthesizes the lessons learned into general and sector-specific recommendations for integrating NAMs into regulatory safety and efficacy assessment frameworks. These recommendations are designed to support the implementation of the European Commission Roadmap for phasing out animal testing addressing needs and opportunities by regulators, industry and CROs for using NAMs as a central source of evidence in safety assessments.
Partners involved
INSTITUTO DE SALUD CARLOS III
Leads WP4 coordination and review panel, coordinating the implementation of the case studies; develops 6 NGRA and 2 C&L case studies (equivalent level of concern for neurotoxicity and for immunotoxicity); and coordinates the integration of the results as recommendations for NAM-based safety assessments
CEHTRA
Leads the development of the conceptual model for the case studies and 4 C&L case studies (acute toxicity, skin sensitization, aquatic toxicity)
aquatox
Leads 2 C&L ecotoxicity case studies (aquatic toxicity)
INERIS
Leads 3 PoD derivation case studies (developmental neurotoxicity, PE); PBPK modelling
sanofi
Leads 4 pharmaceutical safety/efficacy case studies (heart, brain, liver and intestine toxicity)
NETRI
Provides feedback and insights on NAM data and models for the case studies
LYONBIOPOLE
Organizes multi-sector consultation workshop
BIOREGIO STERN
Supports stakeholder engagement on NAM frameworks and multi-sector workshops
AXELERA
Supports stakeholder consultation on NAM frameworks
UMWELTBUNDESAMT
Leads critical assessment of case studies
Deliverables
upcoming
Latest News & Updates
The conceptual model for the case studies (D4.1) has been finalized and used for the selection of the case studies.
The ongoing case studies are summarized in the following figure: