First-in-man and IND

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> Discovery and drug candidate selection

> First-in-man and IND

> From IND to NDA

Before initiating a clinical trial program with a novel pharmaceutical drug candidate, the safety of the drug candidate must be investigated in a series of preclinical safety studies. To support initial first-in-man clinical trials (CTA, IND), the following general preclinical safety package is usually applicable :

  • Dose range-finding studies to select appropriate dose levels
  • Two repeat-dose toxicology studies in a rodent and a non-rodent species; usually over 28 days, or at least as long as the planned clinical treatment length
  • An ICH standard genotoxicity battery (not normally required for biopharmaceuticals); two in vitro studies for gene/chromosome damage in bacteria and in mammalian cells, and one in vivo study for chromosome damage in rodents
  • An ICH safety pharmacology core battery which may be incorporated into the repeat-dose toxicology studies, in particular for biopharmaceuticals
  • Local tolerance investigation of potential adverse affects at the application site; investigation of potential allergenicity and photosafety hazards should also be considered
  • Potential effect on fertility
  • Pharmacokinetics/toxicokinetics must be included in all studies to document that the animals in the toxicology studies are exposed to the test drug and to predict the pharmacokinetic properties of the drug candidate in humans
  • Assessment of anti-drug antibody formation for protein-based biopharmaceuticals