Reproductive and developmental toxicity Table 7: Summary of reproductive and developmental toxicity studies: Species NOAEL Dose (mg/kg)/ AUC Study / GLP Dosing period (mg/kg) Major findings Route (ng.h/ml) Number of animals Fertility (M) Fertility (F) Embryo-foetal F0 development F1 Peri&postnatal Table 8: Points to be taken into account for the calculation of the post-treatment contraception period PRODUCT Half-life (t½) in human Genotoxicity Carcinogenicity Calculation based on 5 half-lives Woman post-treatment contraception period Man post-treatment contraception period Juvenile toxicity Table 9: Summary of juvenile animal studies NOEL/ Species Duration AUC Dose NOAEL Major findings (age) and route (ng.h/ml) (mg/kg/jday) Local tolerance # Questions Yes No If no, justify 1 Is local toxicity studied : (skin, eye…) signs of irritation, inflammation, histology…? Phototoxicity # Questions Yes No If no, justify 1 Is photosafety studied ? Other studies Provide other non-clinical studies Grounds for doses selection for clinical trials Starting dose Indicate the non-clinical endpoints used HED HNSTD and MRSD MABEL PAD STD for the selection of the starting dose: (NOAEL) other
Reproductive and developmental toxicity Table 7: Summary of reproductive and developmental toxicity studies: Species Study / GLP Number of animals Dose (mg/kg)/ Route Dosing period NOAEL (mg/kg) AUC (ng.h/ml) Major findings Fertility (M) Fertility (F) Embryo-foetal development F0 F1 Peri&postnatal Table 8: Points to be taken into account for the calculation of the post-treatment contraception period PRODUCT Half-life (t½) in human Genotoxicity Carcinogenicity Calculation based on 5 half-lives Woman post-treatment contraception period Man post-treatment contraception period Juvenile toxicity Table 9: Summary of juvenile animal studies Species (age) Dose Duration and route NOEL/ NOAEL (mg/kg/jday) AUC (ng.h/ml) Major findings Local tolerance # Questions Yes No If no, justify 1 Is local toxicity (skin, eye…) studied : signs of irritation, inflammation, histology…? Phototoxicity # Questions Yes No If no, justify 1 Is photosafety studied ? Other studies Provide other non-clinical studies Grounds for doses selection for clinical trials Starting dose Indicate the non-clinical endpoints used for the selection of the starting dose: HED (NOAEL) MRSD MABEL PAD STD HNSTD and other
98e34c5eee7c7b729931542a66c80a1a.docx