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 hazard identification.

• The assay uses gene expression profiling of 196 genes in dendritic cells and machine learning to classify chemicals as sensitizers or non-sensitizers, offering mechanistic differentiation from other assays.

• GARD-skin is particularly effective for hydrophobic substances and complex mixtures, outperforming traditional assays like h-CLAT in predictive accuracy.

• The method is validated for both hazard identification and CLP potency subcategorization, with high correlation to human and animal reference data.

• GARD-skin can be used as a standalone assay for non-regulatory purposes and is adaptable for challenging substances, including nanomaterials and hydrolytically unstable chemicals.

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 yields higher predictive accuracy than combined approaches, especially for challenging test materials.

• Collaborative studies with regulatory and industry partners confirm GARD-skin's applicability for agrochemical formulations and complex mixtures.

• The dose response version of GARD-skin enables quantitative potency prediction, correlating well with human NESIL and LLNA AC3 values.

• GARD-skin medical device adaptation has achieved pre-validation and is being used for regulatory submissions, including CE marking in Europe.

Regulatory and practical considerations

• GARD-skin is now included in OECD TG 497, broadening regulatory acceptance for non-animal skin allergy testing and is expected to boost demand from chemical and cosmetics industries.

• Selection of testing strategy should reflect the physicochemical properties of test materials, with GARD-skin and EpiSensA recommended for hydrophobic substances.

• The assay supports a wide range of solvents beyond water and DMSO, facilitating testing of diverse chemical classes.

• Ongoing protocol modifications address hydrolytically unstable substances and nanomaterials, with promising initial results.

• Regulatory acceptance varies by region, with European notified bodies more open to GARD-skin data than the US FDA at present.