Session 1: Validation of alternative methods

Validation as a step towards the acceptance of alternative methods for safety assessment

Prof. Maurice P. Whelan


European Commission Joint Research Centre, Institute for Health and Consumer Protection, European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Ispra, Italy


Head of Systems Toxicology Unit and EURL ECVAM


Acceptance of alternative (non-animal) methods for regulatory decision making is typically context dependent and relies on many factors.

Validation is usually an essential step towards acceptance by regulators and end-users and although the process employed can vary, ultimately the aim is to demonstrate the reliability and the relevance of a method or approach and the associated limitations and uncertainties.

Reliability assessment focuses on the transferability and reproducibility of a method and although this is primarily a technical task, it can prove the most resource and time consuming part of a validation study. The relevance of a method can be described on many different levels, such as the ability of a method to capture a specific toxicological mechanism or pathway, or the accuracy with which the method can predict an apical in vivo endpoint.

Since a comprehensive toxicological assessment using alternative approaches requires a combination of complementary methods, the relevance of an individual method is relative and related to the value of information it provides in context of an integrated assessment and testing strategy. This poses a challenge in that methods are typically proposed for validation before any specific strategies have been defined to describe the use-context.

We need therefore to continue to evolve many aspects of validation practice to be more efficient and effective in evaluating new predictive non-animal approaches to toxicity assessment that have regulatory utility and acceptance.