Research done before human trials — in cells and animals. A necessary step, but not proof that something works or is safe in people.Regulatory agencies require preclinical evidence (safety pharmacology, toxicology, mechanism characterization) before permitting Phase I human trials. Preclinical evidence establishes that a compound has a plausible mechanism, is not immediately lethal in animals at relevant doses, and has sufficient rationale to justify human exposure. It does not establish human efficacy or safety. The failure rate from promising preclinical results to successful human trials is high — estimates range from 85–95% of compounds that enter Phase I never reaching approval.