Current nonclinical testing paradigm to allow clinical entry for pharmaceutical drug candidates

Nonclinical safety testing (pharmacology, ADME and toxicology studies) needs to occur to support First-InHuman clinical entry for pharmaceutical drug candidates. Examination of the study package from the content of Investigator Brochures (IBs) for 32 small (non-oncology) molecules used to support such entry over a 4-year period (2020-2023) showed that a mean of 38 nonclinical studies were performed per molecule with pharmacology, ADME and toxicology testing contributing 37 %, 39 % and 24 % of the studies, respectively. Examination of IBs used to support clinical entry of 15 small molecule oncology drugs gave similar values of 43 studies contributing 37 %, 42 % and 21 %, respectively. Examination of IBs for 16 biopharmaceuticals showed a mean number of 19 studies per molecule with pharmacology, ADME and toxicology testing contributing 84 %, 5% and 11 % of the studies, respectively. Overall, for both small molecule and biopharmaceutical drug candidates, similar numbers of pharmacology studies were performed but the approximately 50 % fewer studies for biopharmaceuticals was due to considerably limited ADME and toxicology testing. Comment will be made on how the current study package could be refined (a 3Rs approach) to reduce animal use.