title: Opportunities to Apply the 3Rs in Safety Assessment Programs.
abstract: Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans.
authors.affiliation: Fiona Sewell, PhD, is a Programme Manager in Toxicology and Regulatory Sciences at the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), London, UK. Joanna Edwards, PhD, is a Programme Manager in Technology Development at the NC3Rs, London, UK. Helen Prior, PhD, is a Programme Manager in Drug Development at the NC3Rs, London, UK. Sally Robinson, PhD, is Head of Laboratory Animal Sciences at AstraZeneca, Alderley Park, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Sewell
authors.affiliation: Fiona Sewell, PhD, is a Programme Manager in Toxicology and Regulatory Sciences at the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), London, UK. Joanna Edwards, PhD, is a Programme Manager in Technology Development at the NC3Rs, London, UK. Helen Prior, PhD, is a Programme Manager in Drug Development at the NC3Rs, London, UK. Sally Robinson, PhD, is Head of Laboratory Animal Sciences at AstraZeneca, Alderley Park, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Fiona Sewell, PhD, is a Programme Manager in Toxicology and Regulatory Sciences at the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), London, UK. Joanna Edwards, PhD, is a Programme Manager in Technology Development at the NC3Rs, London, UK. Helen Prior, PhD, is a Programme Manager in Drug Development at the NC3Rs, London, UK. Sally Robinson, PhD, is Head of Laboratory Animal Sciences at AstraZeneca, Alderley Park, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Prior
authors.affiliation: Fiona Sewell, PhD, is a Programme Manager in Toxicology and Regulatory Sciences at the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), London, UK. Joanna Edwards, PhD, is a Programme Manager in Technology Development at the NC3Rs, London, UK. Helen Prior, PhD, is a Programme Manager in Drug Development at the NC3Rs, London, UK. Sally Robinson, PhD, is Head of Laboratory Animal Sciences at AstraZeneca, Alderley Park, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Robinson
mesh_terms: D000826:Animal Testing Alternatives; D000827:Animal Welfare; D000818:Animals; D055808:Drug Discovery; D006801:Humans
keywords: 3Rs; drug development; pharmaceuticals, safety assessment; reduction; refinement; replacement