At Society of Toxicology (SOT) annual meeting in Orlando (#SOT2025), I had the pleasure of presenting our collaborative poster, “Characterization of Structural Clusters for Extractables and Leachables (E&L) Risk Assessment.” The project, conducted in collaboration with global regulatory, pharmaceutical, and toxicology experts, tackles the characterization of the chemical space of extractables and leachables (E&Ls), i.e., substances that can migrate from pharmaceutical packaging into drug products.
As the ICH continues to develop guidance (notably Q3E) for E&Ls, our work aims to support regulatory science by structurally characterizing a dataset of approximately 1,200 potential E&L chemicals. Using cheminformatics tools, we clustered these chemicals Tier-1 clusters and Tier-2 subclusters, offering a new level of resolution into E&L structural diversity.
Key insights emerged:
- Most E&L substances had molecular weights under 250 Da, and the majority exhibited moderate hydrophobicity (LogP 0–5).
- Only a small percentage (3%) showed strong dermal sensitization potential, and 9% were flagged as potential mutagens, findings consistent with previous literature.
- The clustering process not only visualized chemical diversity but enables identification of representative, data-rich substances that can may serve as surrogates for structurally similar, data-poor compounds.
Stay tuned! This is just one step toward a more robust framework for understanding and managing E&L risks in pharmaceuticals.
We’d love to hear from you! Don’t hesitate to reach out if you’d like to chat more about this topic!