The 3Rs (namely, Replacement, Reduction, and Refinement) and harm-benefit analysis (HBA) are central to the evaluation procedures regulating the use of animals in biomedical research. These deeply intertwined frameworks frequently overlap conceptually and are often confused. This paper examines whether these frameworks are grounded in the same moral factors to descriptively investigate the normative functions attributed to them in recent publications and in Directive 2010/63/EU. To this end, the strategies for operationalising the 3Rs and HBA were examined to infer the ethical issues researchers typically face by identifying and clustering the most recurring themes and arguments mentioned in the literature. This conceptual ‘unpacking’ process concludes that the moral factors underpinning both frameworks centre on two main normative anchorage points: the Animal and Epistemological foci. A set of normative, operational criteria relevant to ethics committees when assessing research project proposals was also developed.

This article understands risk dialectically as a decision-making resource stressing probability but as also giving rise to further uncertainties. It shows that the panel report in EC – Biotech reflects an understanding of risk as decision-making that is deterministic and leaves little room for the application of precautionary approaches and non-scientific factors. It submits that such an approach is unsuitable for novel technologies with limited background knowledge and reduces the accountability of risk regulators. A different approach is put forth, which allows members greater scope for precautionary action while preventing trade protectionism. The article concludes that law can enhance its authority and epistemic validity through scientific evidence but only if it recognizes science's epistemic and its own limitations. Law has to approach science as contested knowledge and risk regulation as political decision-making, leading – inevitably – to more indeterminate solutions to legal conflicts.