International Harmonization and Cooperation in the Validation of Alternative Methods.

The development and validation of scientific alternatives to animal testing is important not only from an ethical perspective (implementation of 3Rs), but also to improve safety assessment decision making with the use of mechanistic information of higher relevance to humans. To be effective in these efforts, it is however imperative that validation centres, industry, regulatory bodies, academia and other interested parties ensure a strong international cooperation, cross-sector collaboration and intense communication in the design, execution, and peer review of validation studies. Such an approach is critical to achieve harmonized and more transparent approaches to method validation, peer-review and recommendation, which will ultimately expedite the international acceptance of valid alternative methods or strategies by regulatory authorities and their implementation and use by stakeholders. It also allows achieving greater efficiency and effectiveness by avoiding duplication of effort and leveraging limited resources. In view of achieving these goals, the International Cooperation on Alternative Test Methods (ICATM) was established in 2009 by validation centres from Europe, USA, Canada and Japan. ICATM was later joined by Korea in 2011 and currently also counts with Brazil and China as observers. This chapter describes the existing differences across world regions and major efforts carried out for achieving consistent international cooperation and harmonization in the validation and adoption of alternative approaches to animal testing.

The ECVAM Scientific Information Service (SIS).

This article provides a general view about the main Scientific Information Service (SIS) projects and their current status. The SIS was established in 1996, to best achieve one of the four main obligations of the European Centre for the Validation of Alternative Methods (ECVAM), as required by the European Commission and Parliament, to establish and maintain a database on alternative procedures to animal experimentation. Two projects have been carried out: the SIS databases providing factual information on various aspects of animal alternatives and the ECVAM Thesaurus. The first online version of selected SIS databases was published on the Internet in 2001. The ECVAM Thesaurus will be made available for practical applications in 2004, and the general website of the whole ECVAM unit has been available since autumn 2002.

A modular approach to the ECVAM principles on test validity.

The European Centre for the Validation of Alternative Methods (ECVAM) proposes to make the validation process more flexible, while maintaining its high standards. The various aspects of validation are broken down into independent modules, and the information necessary to complete each module is defined. The data required to assess test validity in an independent peer review, not the process, are thus emphasised. Once the information to satisfy all the modules is complete, the test can enter the peer-review process. In this way, the between-laboratory variability and predictive capacity of a test can be assessed independently. Thinking in terms of validity principles will broaden the applicability of the validation process to a variety of tests and procedures, including the generation of new tests, new technologies (for example, genomics, proteomics), computer-based models (for example, quantitative structure-activity relationship models), and expert systems. This proposal also aims to take into account existing information, defining this as retrospective validation, in contrast to a prospective validation study, which has been the predominant approach to date. This will permit the assessment of test validity by completing the missing information via the relevant validation procedure: prospective validation, retrospective validation, catch-up validation, or a combination of these procedures.

ECVAM's response to the changing political environment for alternatives: consequences of the European Union chemicals and cosmetics policies.

The European Centre for the Validation of Alternative Methods (ECVAM) has restructured its services by directly targeting the animal tests that need to be replaced. In view of the short time-lines for making available and implementing validated methods, ECVAM is offering to steer the process by bringing together the inputs of stakeholders and encouraging the early involvement of regulators. In essence, steering groups formed by ECVAM senior staff, and complemented with external experts, will carry out the project management and will coordinate the various inputs.

The ECVAM Scientific Information Service (SIS).

The aim of this ECVAM Status Seminar was to critically review the contributions made by ECVAM in relation to its four main task. The establishment and maintenance of the ECVAM Scientific Information Service (SIS) is a precise means of fulfilling one of these four principal duties of ECVAM. The major achievements of the SIS, and the efforts required to achieve them, are discussed, together with the immediate future for the SIS.