Moving the Needle on New Approach Methods (NAMs) in Predictive Toxicology and Risk Assessment: Integrating Methods Towards Regulatory Acceptance

Achieving regulatory acceptance of New Approach Methods (NAMs) is critical to advancing predictive toxicology and reducing reliance on traditional animal models. At Biobide, we have developed and qualified the zebrafish developmental defects assay following the ICH S5(R3) guideline, demonstrating data robustness, reproducibility, and regulatory relevance, even to complement or substitute animal studies for regulatory purposes. Our assay evaluated 32 reference compounds, achieving Accuracy: 89.66%, Sensitivity: 88.46% and Specificity and Repeatability: 100%
These results were obtained through three blinded biological replicates, with teratogenic classification based on LC50/EC50-derived Teratogenic Index (TI a 2). Benchmark Concentration (BMC) values showed strong correlation with mammalian LOAEL Cmax data, reinforcing the zebrafish model's translational value. Bioavailability studies further refined inconclusive results, highlighting the importance of internal exposure metrics. In parallel, Biobide's ecotoxicity and endocrine disruption platforms—based on OECD guidelines and transgenic zebrafish lines—enable high-throughput screening of environmental and pharmaceutical compounds. These assays integrate morphological, molecular (RT-qPCR), and fluorescence endpoints, offering mechanistic insights into estrogenic and thyroid pathway disruption. Our work underscores the need for high-quality, reproducible data to support regulatory confidence in NAMs. The zebrafish model provides a whole-organism vertebrate system that bridges in vitro and mammalian testing, aligning with 3Rs principles and international guidelines. This presentation will share qualification and validation data, regulatory alignment strategies, and a tiered testing framework to accelerate NAMs' adoption in risk assessment.