Overcoming barriers to validation of non-animal partial replacement methods/Integrated Testing Strategies: the report of an EPAA-ECVAM workshop.

The use of Integrated Testing Strategies (ITS) in toxicological hazard identification and characterisation is becoming increasingly common as a method for enabling the integration of diverse types of toxicology data. At present, there are no existing procedures and guidelines for the construction and validation of ITS, so a joint EPAA WG5-ECVAM workshop was held with the following objectives: a) to investigate the role of ITS and the need for validation of ITS in the different industry sectors (pharmaceuticals, cosmetics, chemicals); b) to formulate a common definition of ITS applicable across different sectors; c) to explore how and when Three Rs methods are used within ITS; and d) to propose a validation rationale for ITS and for alternative methods that are foreseen to be used within ITS. The EPAA provided a platform for comparing experiences with ITS across different industry sectors. It became clear that every ITS has to be adapted to the product type, R&D stage, and regulatory context. However, common features of ITS were also identified, and this permitted the formulation of a general definition of ITS in a regulatory context. The definition served as a basis for discussing the needs, rationale and process of formal ITS validation. One of the main conclusions was that a formal validation should not be required, unless the strategy will serve as full replacement of an in vivo study used for regulatory purposes. Finally, several challenges and bottlenecks to the ITS validation were identified, and it was agreed that a roadmap on how to address these barriers would be established by the EPAA partners.

Management of an integrated project (Sens-it-iv) to develop in vitro tests to assess sensitisation.

Sens-it-iv is an integrated project, funded by European Commission Framework Programme 6, the overall objective of which is to develop in vitro tests and test strategies to be used by the chemical, cosmetic and pharmaceutical industries to assess the risk for potential contact and respiratory sensitisers. Such tests, once formally validated and accepted, will permit the evaluation of the sensitising potential of existing and new chemical entities and the products of the European industries for classification and labelling, as required by the new EU REACH legislation on chemicals, or for the purpose of risk assessment as required by the 7th Amendment to the EU Cosmetics Directive. Sens-it-iv involves 28 partners, representing industries, universities and regulatory bodies, including various institutes in the EU Member States and different competencies, all with the common aim of achieving a final deliverable - increasing the safety of consumer products, whilst reducing animal experimentation. This paper provides an overview of the structure of the project and a detailed description of the organisation of its management.

The contributions of the European cosmetics industry to the development of alternatives to animal testing: dialogue with ECVAM and future challenges.

COLIPA (the European Federation of the Cosmetics Industry) represents 24 international companies and 2000 small and medium-sized enterprises. Together with ECVAM, COLIPA has been involved in the development and validation of alternative methods since the beginning of the validation efforts. The work of the Steering Committee on Alternatives to Animal Testing (SCAAT) is based on collaboration between companies, but also with academia, trade associations, the Scientific Committee on Cosmetics and Non-Food Products (SCCNFP), European Commission Directorates General, and ECVAM. Some success has been achieved, but some validation efforts have failed. One lesson is that the search for alternatives requires a lot of humility.

The research programme of SCAAT.

The European Federation of the Cosmetics Industry (COLIPA's) Steering Committee on Alternatives to Animal Testing (SCAAT) is currently focusing its research activity on two areas: skin tolerance and eye irritation. SCAAT has set up two three-year projects on skin sensitisation, one three-year project on skin irritation and one three-year project on eye irritation. The sensitisation projects aim at the standardisation and optimisation of a method involving human dendritic cells and the identification of upregulated genes following exposure of these cells to chemicals. The skin irritation project aims to identify new markers of irritation with the help of genomic and proteomic technologies. These three projects will be carried out by industry. The scope of the eye project is to identify new in vitro endpoints, predictive of the in vivo response to chemical injury. It involves collaboration with ophthalmologists from the Universities of Aachen and Bristol. The team in Aachen will try to identify whether the kinetics and patterns of changes in physiological function and signals of injury released from the cornea in vitro can predict a chemical's potential to damage the eye, with a focus on recovery. All these projects aim at developing and optimising alternative methods for further prevalidation.