Understanding the lengthy process to replace the draize test

The urgency of the transition to replace animal tests in the safety assessment of cosmetics, pharmaceuticals and chemicals was triggered by societal resistance to animal testing and the scientific dispute concerning the value of animal testing. Since the 1980s, the European Union (EU) has developed policies to stimulate the development of innovative methods to replace animal studies. However, for regulatory testing, these policies have not been very effective, since only a few regulatory safety tests in animals (among which the Draize test, skin sentisation test) have been (partly) replaced by innovative methods. The few 'successful' replacement processes were laborious and took decades. In order to understand why transitions toward the replacement of animal tests in the regulatory safety assessment take so much time, these transitions need to be systematically studied, taking into account all stakeholders involved in the development and acceptance of innovative methods. We used a framework, called the combined Technological Innovation System-Multi Level Perspective (TIS-MLP) framework, to systematically study transitions, and thereby elucidate the mechanisms that complicate them. We focused on the lengthy transition toward innovative methods for the Draize test. Eye irritation testing can be considered a pioneer in the development and validation of innovative methods to replace animal tests. Several innovative methods have been developed since the early 1980s, and major multi-laboratory validation studies were undertaken as early as the 1990s. It took until 2004 before a thorough review was carried out to advance the validation of innovative methods. Finally, two tests were approved by the OECD in 2009, to partially replace the Draize test - the Bovine Corneal Opacity and Permeability assay (BCOP) and the Isolated Chicken Eye (ICE) test. Both of these tests were already published in 1985, well over 20 years before regulatory acceptance. This study elucidates why this transition was so lengthy. Based on the combined TIS-MLP analysis it can be concluded that, despite the EU policy to stimulate the development of innovative methods and societal resistance, there was initially a lack of resources to further develop innovative methods. The EU ban on the use of animal tests for cosmetics was the key to solving this issue. Without this pressure on manufacturers, there was a lack of incentives for them to invest in innovative methods. In a later stage, the innovation process was impeded due to a lack of guidance with respect to the validation process and unrealistic validation endpoints. In none of the six validation studies, were innovative methods approved. Years of successful use of the Draize test made it the 'gold standard' in the validation studies. The performance of the innovative methods was judged in relation to the Draize test, not taking into account the actual flaws of that test. Due to the pressure of the EU ban on animal tests for cosmetics, it was considered necessary to change the validation strategy. Finally, only a review of the six validation studies finally convinced the OECD to accept the ICE and BCOP in 2009