02215nas a2200289   4500000000100000000000100001008004100002260001500043653000800058653000900066653001300075653001900088653001200107653002000119653001600139653001900155100002000174700001800194700001800212700002500230700002700255245006300282300001200345490000700357520154700364022001401911       2022                            d  c2022-08-1910a3Rs10aNAMs10aThree Rs10aanimal testing10ahistory10apharmaceuticals10aregulations10asafety testing1 aDoortje Swaters1 aAnne van Veen1 aWim van Meurs1 aJanette Ellen Turner1 aMerel Ritskes-Hoitinga00aA History of Regulatory Animal Testing: What Can We Learn?  a322-3290 v503 aThe contemporary pharmaceutical industry is voicing growing concerns about the translatability and reproducibility of animal models. In addition, the usefulness of certain of the required regulatory safety tests in animals is being increasingly questioned. It remains difficult, however, to make the move toward alternative testing methods, not least because of legislative demands. A historical analysis was performed, in order to study how the mandatory animal studies in legislative requirements came about. This article reflects on the role that specific public health disasters played in the creation of (more) regulatory requirements for animal testing. It will show how the regulatory changes prompted by the sulfanilamide elixir disaster in the 1930s and the thalidomide disaster in the early 1960s were based on the belief that extensive animal testing would prevent similar future human health tragedies. As scientists increasingly highlight issues with translatability between non-human animals and humans, the belief that current regulatory requirements ensure safety becomes more difficult to maintain. In addition, it means that some of the regulations now in place require animal tests that do not contribute to the safety of a drug, as shown in a third case study of the court case by Vanda industries against the FDA. We finally argue that regulations should be critically examined and altered where necessary, so that they are no longer a barrier in the transition toward animal-free testing and more human-relevant science.  a0261-1929