The main purposes of toxicological assessments are:
(1) to characterize the toxicity profile of any NCE, with identification of target organs and the potential to induce these effects,
(2) to evaluate the risk by determining if they can occur in humans (based on PK, metabolism, or species specificity) and to assess whether the risk is acceptable (given the indication or the novelty of the approach) and lastly
(3) to manage the risk by identification of safety parameters for clinical monitoring or contraindication recommendation.
Regulatory environment
Most appropriate nonclinical safety packages will be proposed considering up-to date guidelines from ICH & EMA, FDA, OECD, as well as GLP, ethic principals and 3R rules (including for instance ICH S7, ICH S9, ICH M3, ICH M7 etc…). It will include all required safety pharmacology, toxicology and genotoxicity studies. Additional studies could be recommended on a case-by-case basis including dedicated local tolerance, immunotoxicity, photosafety or juvenile toxicity studies for instance.
Determination of safety margins
Based on efficacy, toxicology and pharmacokinetic data obtained, safety margins could be derived and support FIH entry dose.
