Chairs: José M. Horcas Nieto & Amer Jamalpoor
Congenital abnormalities present a significant cause of child morbidity and mortality. Although genetic factors play a role in these, maternal exposure to medications and environmental pollutants has been shown to be a critical driving factor.
Developmental and reproductive toxicology (DART) represents a complex topic focused on the effects of chemicals, pharmaceuticals or environmental pollutants on embryonic development and throughout the whole reproductive life cycle. Due to the complexity of embryonic development, establishment and validation of in vitro models, able to recapitulate such processes, requires thorough attention.
While several in vitro models have been developed for the assessment of DART, not many have been fully validated and characterised. Validation of these models for toxicological purposes requires adherence to regulatory guidelines to ensure reproducibility, reliability and regulatory acceptance.
Regulatory agencies play a key role in the validation of New Approach Methodologies (NAMS), by defining the acceptance criteria and supporting their incorporation into existing frameworks. Validation studies should take multiple factors into account such as number and nature of the compounds involved, intra- and inter-laboratory reproducibility, and robustness of the assay. Moreover, regulatory agencies require NAMs to identify toxicants within biologically relevant concentrations. A challenge in applying DART-NAMs is translating in vitro data into the corresponding in vivo Human Equivalent Doses (HEDs). Achieving this requires, the combined use of in vitro distribution models together with Physiologically Based Kinetic (PBK) models.
Another crucial aspect of NAMs and their correct use is to properly identify the applicability domain at different stages of the drug development process. For example, NAMs can reduce the amount of animal studies needed when assessing well-known compound classes inducing unequivocal responses.
This session brings together researchers working in several fields of DART, who will present different aspects of development, validation and implementation of in vitro models for the study of DART.
Speakers
- José M Horcas-Nieto – VALIDATION OF THE REPROTRACKER ASSAY FOR REGULATORY USE FOLLOWING ICH SH5 (R3) GUIDELINE
- Jade Houghton – DOSE RESPONSE MODELLING AND TRANSFERABILITY OF REPROTRACKER- AN INDUSTRY PERSPECTIVE
- Styliani Fragki – Supporting NAM-Based Hazard Characterization Through Computational Biokinetic Modeling
- Lena Smirnova – From Synapse to Signal: Human Brain MPS as Next-Generation Tool for DNT Testing
- Peter Theunissen – Advancing Regulatory Acceptance of NAMs for Developmental Toxicity: Insights from ICH S5(R3)