Associate Research Fellow Pfizer Research and Development Groton, Connecticut, United States
ICH Q3A/B guidelines are not intended to be applied to drug substance or product used during the clinical research phase of development and durationally adjusted qualification thresholds are not included. Recent publications have outlined approaches that support clinical development qualification limits that are higher than those expected for registration. The purpose of this study was to evaluate whether these durationally adjusted qualification limits are supported by in vivo toxicology data. Data from sub-acute and sub-chronic repeat dose toxicity studies were gathered and no observed (adverse) effect level (NO(A)EL) data was summarized. Tthe 5th percentile of the distribution of NO(A)ELs from sub-acute and sub-chronic repeat dose toxicology studies were 2.3 mg/kg/day and 0.62 mg/kg/day, respectively (i.e. 115 mg/day or 31 mg/day assuming a 50 kg human bodyweight). This analysis supports durationally adjusted NMI qualification limits for pharmaceuticals.
