A framework to support the application of the OECD guidance documents on (Q)SAR model validation and prediction assessment for regulatory decisions

Abstract

Advances in the development and application of in silico models in toxicology has been recognised by two OECD guidance documents (69: Guidance Document On The Validation Of (Quantitative) Structure-Activity Relationship [(Q)SAR] Models and 386: (Q)SAR Assessment Framework: Guidance for the regulatory assessment of (Q)SAR models, predictions, and results based on multiple predictions) published in 2007 and 2023 respectively. The former outlines criteria for appropriate model validation, whilst the latter provides guidance around assessing predictions derived from them. The concepts and criteria described within these guidelines have been used to establish a framework to support both model builders and those applying them to support regulatory decisions. Herein we demonstrate how to meet those criteria and propose where further guidance is essential for ensuring the consistent, confident, and safe application of in silico models in support of regulatory decisions.