Workshop on acceleration of the validation and regulatory acceptance of alternative methods and implementation of testing strategies

Abstract

This report describes the proceedings of the BfR-RIVM workshop on validation of alternative methods which was held 23 and 24 March 2017 in Berlin, Germany. Stakeholders from governmental agencies, regulatory authorities, universities, industry and the OECD were invited to discuss current problems concerning the regulatory acceptance and implementation of alternative test methods and testing strategies, with the aim to develop feasible solutions. Classical validation of alternative methods usually involves one to one comparison with the gold standard animal study. This approach suffers from the reductionist nature of an alternative test as compared to the animal study as well as from the animal study being considered as the gold standard. Modern approaches combine individual alternatives into testing strategies, for which integrated and defined approaches are emerging at OECD. Furthermore, progress in mechanistic toxicology, e.g. through the adverse outcome pathway approach, and in computational systems toxicology allows integration of alternative test battery results into toxicity predictions that are more fine-tuned to the human situation. The road towards transition to a mechanistically-based human-focused hazard and risk assessment of chemicals requires an open mind towards stepping away from the animal study as the gold standard and defining human biologically based regulatory requirements for human hazard and risk assessment.

Workshop on the validation and regulatory acceptance of innovative 3R approaches in regulatory toxicology – Evolution versus revolution

“…(Aldert H. Piersma, RIVM) Following up from the first BfR-RIVM workshop (Piersma et al, 2018a), the scene of this workshop was set by introducing the concept of evolution versus revolution in innovating toxicity testing (Scialli et al, 2018). The historic sequence of human safety testing has proceeded through the introduction of animal methods in the mid-20 th century, followed by development of in vitro alternatives in later decades.…”

“…As mentioned, a survey on needs with respect to the various decision contexts would be helpful, and work is ongoing in that area (e.g. (Strickland et al, 2018), (Daniel et al, 2018), (Choksi et al, 2018) (Piersma et al 2018a), and focus on reliability.…”

“…Case studies have been suggested, during the previous BfR-RIVM workshop, to have the potential to serve as the new validation or 'quality assurance' tool in order to accelerate the validation process of alternative methods and testing strategies (Piersma et al, 2018a). The breakout group addressed the potential advantages, challenges, uses and considerations of case studies for innovating the validation of novel 3R approaches in regulatory toxicology.…”

“…Workshop on validation and regulatory acceptance of alternative methods and test strategies". During this workshop, regulatory authorities, test method developers, and users from academia, industry and CRO as well as experts participating in the Test Guidelines Programme of the Organization for Economic Cooperation and Development (OECD) discussed the drivers and barriers concerning implementation of innovative 3R approaches in regulatory toxicology (Piersma et al, 2018a). As a result of the first workshop, two major scenarios allowing the implementation of alternative testing strategies were identified, an evolutionary and a revolutionary one.…”

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“…An example of such an initiative is the SIN list (http://chemsec.org/sin-list/) maintained by the NGO ChemSec. However, there are significant obstacles to such an approach, such as funding limitations, or issues related to primary research communication and study quality (Agerstrand et al, 2017), but also integration and regulatory acceptance of alternative toxicity assessment methods, such as in silico predictions or in vitro tests (Piersma et al, 2018). Furthermore, peer-reviewed literature also tends to be biased towards the better-known substances, and switching the academic attention to the next group of 'emerging' substances tends to have a lengthy lag period (Bao et al, 2015;Li et al, 2018).…”