Principles of QSAR models validation: internal and external

Abstract The recent REACH Policy of the European Union has led to scientists and regulators to focus their attention on establishing general validation principles for QSAR models in the context of chemical regulation (previously known as the Setubal, nowadays, the OECD principles). This paper gives a brief analysis of some principles: unambiguous algorithm, Applicability Domain (AD), and statistical validation. Some concerns related to QSAR algorithm reproducibility and an example of a fast check of the applicability domain for MLR models are presented. Common myths and misconceptions related to popular techniques for verifying internal predictivity, particularly for MLR models (for instance cross‐validation,…