Consortium Outputs

NAM implementation success and failures

Institute for Evidence-Based Toxicology (IEBT) –  task leader WP3

Context: Beyond Success or Failure: A multistage Process. This report systematically investigated factors that hinder or accelerate the regulatory implementation of NAMs for chemical and pharmaceutical safety assessments. Rather than presenting a binary opposition between “successes” and “failures,” the consortium’s experts redefined this journey as a process of continuous maturation

 Key Take-Home Message: The implementation of NAMs should be viewed as a dynamic maturation process.  The definition of a pipeline from conception to regulatory application is recommended to clearly connect key maturation stages, paving a way to common understanding and efficient communication between all actors involved in the process. 

Findings: The Pillars of Trust: Validation, Relevance, and Accessibility. By evaluating 21 representative NAMs, the report proposes key drivers for NAMs’ regulatory implementation. A key feature of NAMs intended for regulatory use is the broad dissemination of their methodologies through scientific publications targeting both scientific and regulatory audiences, publicly available protocols, and commercial availability of essential components. Furthermore, the development of biologically relevant NAMs e.g., by using models aligned with the target population, incorporating metabolic competence, and a clear relationship between measured effects and adverse outcome, was suggested to likely enhance a NAM’s regulatory incorporation.  Finally, formal validation and independent peer review were assessed as critical steps for establishing a method’s scientific credibility with regulatory authorities.

 Key Take-Home Message: The trust required for regulatory incorporation of NAM is primarily built by accessibility to key information, biological relevance and validation. 

Conclusions: Shedding Light on the Actual Use of Alternative Methods. A major obstacle remains: Information on actual use of NAMs for regulatory decision-making is difficult to obtain. Better accessibility on how NAMs are being used and how this use is assessed by regulators would improve our understanding of how NAMs have impacted regulatory decision-making. Identification of NAM shortcomings limiting their regulatory usefulness would allow to effectively target the regulatory needs with improved or novel NAMs, accelerating the transition to NAM-based risk assessment.