One science-driven approach for the regulatory implementation of alternative methods: A multi-sector perspective.

EU regulations call for the use of alternative methods to animal testing. During the last decade, an increasing number of alternative approaches have been formally adopted. In parallel, new 3Rs-relevant technologies and mechanistic approaches have increasingly contributed to hazard identification and risk assessment evolution. In this changing landscape, an EPAA meeting reviewed the challenges that different industry sectors face in the implementation of alternative methods following a science-driven approach. Although clear progress was acknowledged in animal testing reduction and refinement thanks to an integration of scientifically robust approaches, the following challenges were identified: i) further characterization of toxicity pathways; ii) development of assays covering current scientific gaps, iii) better characterization of links between in vitro readouts and outcome in the target species; iv) better definition of alternative method applicability domains, and v) appropriate implementation of the available approaches. For areas having regulatory adopted alternative methods (e.g., vaccine batch testing), harmonised acceptance across geographical regions was considered critical for broader application. Overall, the main constraints to the application of non-animal alternatives are the still existing gaps in scientific knowledge and technological limitations. The science-driven identification of most appropriate methods is key for furthering a multi-sectorial decrease in animal testing.

Finding synergies for 3Rs - Toxicokinetics and read-across: Report from an EPAA partners' Forum.

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. Currently, lacking toxicokinetic data often prevent the application of read-across. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance. In certain sectors, PBK modelling is being used for risk assessment, but less so in others. Specific activities were identified to facilitate the use of in vitro and in silico toxicokinetic data to support read-across: The collation of available tools indicating the parameters and applicability domains covered; endpoint-specific guidance on toxicokinetics parameters required for read-across; case studies exemplifying how toxicokinetic data help support read-across. Activities to enhance the scientific robustness of read-across include the further user-friendly combination of read-across tools and formal guidance by the authorities specifying the minimum information requirements to justify read-across for a given toxicity endpoint. The EPAA was invited to continue dissemination activities and to explore possibilities to collate a contemporaneous list of open toxicokinetics tools that assist risk assessment.

Knowledge sharing to facilitate regulatory decision-making in regard to alternatives to animal testing: Report of an EPAA workshop.

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a workshop Knowledge sharing to facilitate regulatory decision-making. Fifty invited participants from the European Commission, national and European agencies and bodies, different industry sectors (chemicals, cosmetics, fragrances, pharmaceuticals, vaccines), and animal protection organizations attended the workshop. Four case studies exemplarily revealed which procedures are in place to obtain regulatory acceptance of new test methods in different sectors. Breakout groups discussed the status quo identifying the following facilitators for regulatory acceptance of alternatives to animal testing: Networking and communication (including cross-sector collaboration, international cooperation and harmonization); involvement of regulatory agencies from the initial stages of test method development on; certainty on prerequisites for test method acceptance including the establishment of specific criteria for regulatory acceptance. Data sharing and intellectual property issues affect many aspects of test method development, validation and regulatory acceptance. In principle, all activities should address replacement, reduction and refinement methods (albeit animal testing is generally prohibited in the cosmetics sector). Provision of financial resources and education support all activities aiming at facilitating the acceptance and use of alternatives to animal testing. Overall, workshop participants recommended building confidence in new methodologies by applying and gaining experience with them.

The European Partnership for Alternative Approaches to Animal Testing (EPAA): promoting alternative methods in Europe and beyond.

Here in we introduce the European Partnership for Alternative Approaches to Animal Testing (EPAA) and its activities, which are focused on international cooperation toward alternative methods. The EPAA is one of the leading organizations in Europe for the promotion of alternative approaches to animal testing. Its innovative public-private partnership structure enables a consensus-driven dialogue across 7 industry sectors to facilitate interaction between regulators and regulated stakeholders. Through a brief description of EPAA's activities and organizational structure, we first articulate the value of this collaboration; we then focus on 2 key projects driven by EPAA. The first project aims to address research gaps on stem cells for safety testing, whereas the second project strives for an approach toward demonstration of consistency in vaccine batch release testing. We highlight the growing need for harmonization of international acceptance and implementation of alternative approaches and for increased international collaboration to foster progress on nonanimal alternatives.