Preclinical Trial

Under FDA requirements, a sponsor must first submit data showing that the drug is reasonably safe for use in initial, small-scale clinical studies.

At the preclinical stage, the FDA will generally ask, at a minimum, that sponsors: (1) develop a pharmacological profile of the drug; (2) determine the acute toxicity of the drug in at least two species of animals, and (3) conduct short-term toxicity studies ranging from 2 weeks to 3 months, depending on the proposed duration of use of the substance in the proposed clinical studies.

To meet FDA’s requests, during preclinical drug development, a sponsor evaluates the drug’s toxic and pharmacologic effects through in vitro and in vivo laboratory animal testing. Genotoxicity screening is performed, as well as investigations on drug absorption and metabolism, the toxicity of the drug’s metabolites, and the speed with which the drug and its metabolites are excreted from the body. As a summary, the following data are needed to fulfill the requirements, including:

  • ADME
  • Acute Pharmacology
  • Metabolic Stability
  • Genomic Biomarker Analysis
  • Protein Biomarkers
  • CYP Screening
  • Assay Metabolites
  • Pharmacogenomics/Toxicogenomics
  • In vitro Toxicity
  • Mutagenecity
  • In vivo Toxicity


There is no ‘one size fits all’ approach to the design of preclinical studies. Rather, the preclinical studies must be tailored to the specific investigational agent and the proposed clinical trials. While FDA regulations do not prescribe a standard set of tests for all experimental agents, the FDA has issued guidelines for the selection of preclinical studies.

Two guidance documents that are particularly relevant are: