Tiered Testing Strategy Using Validated In Vitro Assays for the Assessment of Skin and Eye Corrosion/Irritation of Pharmaceutical Intermediates
The safety of workers handling solid pharmaceutical intermediates was assessed using a tiered testing strategy based on regulatory validated in vitro assays. The Top-Down approach was initiated with the in vitro skin corrosion assay (OECD TG 431) followed by the in vitro skin irritation assay (OECD TG 439) using the reconstructed human epidermis model from MatTek Corporation. Of the ten pharmaceutical intermediates tested, nine were predicted to be non-corrosive to skin and were subsequently confirmed as non-irritants. The only intermediate predicted corrosive to skin was further tested using the Corrositex® assay (OECD TG 435) and was assigned a corrosive packing group II classification. Furthermore, three intermediates predicted non-corrosive/non-irritant to skin were tested as 20% dilutions in water in the in vitro Bovine Corneal Opacity and Permeability (BCOP) assay (OECD TG 437) and they were predicted as non-irritants to the eye. Our tiered skin and eye corrosion/irritation testing strategy proved to be a very useful platform for the assessment of the potential safety risk posed to workers during the manufacturing operations used for pharmaceutical intermediates.