title: Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: expert opinions on the state of affairs and the way forward.
abstract: Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being accepted for regulatory risk management purposes. This paper describes the barriers and drivers and options to optimize this acceptance process as identified by two expert panels, one on pharmaceuticals and one on chemicals. To untangle the complex acceptance process, the multilevel perspective on technology transitions is applied. This perspective defines influences at the micro-, meso- and macro level which need alignment to induce regulatory acceptance of a 3R model. This paper displays that there are many similar mechanisms within both sectors that prevent 3R models from becoming accepted for regulatory risk assessment and management. Shared barriers include the uncertainty about the value of the new 3R models (micro level), the lack of harmonization of regulatory requirements and acceptance criteria (meso level) and the high levels of risk aversion (macro level). In optimizing the process commitment, communication, cooperation and coordination are identified as critical drivers.
authors.affiliation: Utrecht University School of Governance (USBO), Bijlhouwerstraat 6, 3511 ZC Utrecht, The Netherlands. Electronic address: m.j.w.a.schiffelers@uu.nl.
authors.forename: Marie-Jeanne W A
authors.initials: MJ
authors.lastname: Schiffelers
authors.affiliation: Utrecht University, Institute for Risk Assessment Sciences (IRAS), P.O. Box 80.178, 3508 TD Utrecht, The Netherlands.
authors.forename: Bas J
authors.initials: BJ
authors.lastname: Blaauboer
authors.affiliation: Utrecht University School of Governance (USBO), Bijlhouwerstraat 6, 3511 ZC Utrecht, The Netherlands.
authors.forename: Wieger E
authors.initials: WE
authors.lastname: Bakker
authors.affiliation: Federal Agency for Medicines and Health Products (FAMHP), Victor Hortaplein 40/40, 1060 Brussels, Belgium.
authors.forename: Sonja
authors.initials: S
authors.lastname: Beken
authors.affiliation: Institute for Translational Vaccinology (InTraVacc), P.O. Box 450, 3720 AL Bilthoven, The Netherlands; Utrecht University, Faculty of Veterinary Medicine, Department Animals in Science and Society, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands.
authors.forename: Coenraad F M
authors.initials: CF
authors.lastname: Hendriksen
authors.affiliation: Orange House Partnership (OHP), Kampendaal 83, 1653 Dworp (Beersel), Belgium.
authors.forename: Herman B W M
authors.initials: HB
authors.lastname: Koëter
authors.affiliation: TNO, P.O. Box 360, 3700 AJ Zeist, The Netherlands; University of Applied Sciences Utrecht (HU), Life Sciences & Chemistry, F.C. Donderstraat 65, 3572 JE Utrecht, The Netherlands.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Krul
mesh_terms: D000826:Animal Testing Alternatives / Q000592:standards*; D000818:Animals; D000830:Animals, Laboratory; D004345:Drug Industry / Q000639:trends*; D005060:Europe; D006801:Humans; D023421:Models, Animal; D008962:Models, Theoretical; D018570:Risk Assessment / Q000379:methods* / Q000592:standards*
keywords: 3R models; Chemicals; Drivers and barriers; Multilevel perspective on technology transitions; Pharmaceuticals; Regulatory acceptance and use; Risk assessment