SenzaGen (SENZA) Status Update summary

Overview of GARD-skin inclusion in OECD Test Guideline 497

• GARD-skin has been officially included in OECD Test Guideline 497, expanding defined approaches for skin sensitization testing and broadening regulatory acceptance for non-animal skin allergy testing.

• The assay provides a mechanistically distinct method for monitoring key event three in the skin sensitization adverse outcome pathway.

• GARD-skin uses gene expression profiling of 196 genes in dendritic cells and genomics with machine learning to classify chemicals as sensitizers or non-sensitizers.

• The method is particularly effective for hydrophobic substances and complex mixtures, outperforming traditional assays like h-CLAT and addressing previously unmet testing needs.

• GARD-skin can be used for hazard identification, CLP potency classification, and is expected to boost demand from chemical and cosmetics industries.

Case studies and performance data

• Replacing h-CLAT with GARD-skin in defined approaches significantly improves predictive performance for hydrophobic materials.

• GARD-skin as a standalone assay often provides higher predictive accuracy than combined approaches.

• Testing with GARD-skin demonstrated high sensitivity, specificity, and balanced accuracy compared to h-CLAT in challenging test materials.

• The assay is applicable to both neat chemicals and complex agrochemical formulations, maintaining high accuracy even with difficult-to-test substances.

• GARD-skin dose response modification enables continuous prediction of skin sensitizing potency, correlating well with human reference data.

Regulatory and practical considerations

• GARD-skin is suitable for use in both regulatory and non-regulatory contexts, with substantial supporting data for various chemical domains.

• The assay can be adapted for hydrolytically unstable substances and nanomaterials, with ongoing protocol development.

• Regulatory acceptance varies: GARD-skin data has supported CE marking in Europe, while US FDA reviews are ongoing on a case-by-case basis.

• The method is compatible with a wide range of solvents, including highly non-polar options, enhancing its applicability.

• GARD-skin medical device version is progressing toward ISO standardization and broader regulatory approval.