Regulatory authorities will not approve a phase 1 trial on a new drug unless there is strong evidence that it is unlikely to cause harm when given to people. A wide range of in vitro and in vivo studies are typically carried out to assess safety before use in people, many of them mandated by regulatory authorities.

In vitro toxicology studies

Multiple tests can be carried out to assess the effects of drugs on key cellular processes and proteins:

  • Cytotoxicity assays determine whether the drug has any harmful impact on cells and key cellular structures and processes.
  • hERG (human ether-a-gogo-related gene) and other receptor assays provide data on interactions with key protein structures on cells, which might interfere with their function and cause significant side effects (cardiac issues in the case of hERG).
  • In vitro absorption, distribution, metabolism and excretion (ADME) studies are used to explore how drug compounds are taken up and metabolized by cells. This provides important information on their properties, and whether they are suitable to be used as drugs, but can also provide insight into toxic effects on cell function. Examples include the Caco-2 assay of uptake by cells and microsomal stability assays, which assess breakdown of compounds within cells.

In vivo toxicology studies

In vivo toxicology studies complement in vitro studies by providing data on safety in living animals, usually rodents. Several types of in vivo toxicology study are typically carried out:

  • Dose-ranging studies: These are carried out in mice or rats and assess the effects of different doses of an investigational drug, given as a single dose or in multiple doses, on a wide range of clinical signs, physiological parameters, and tissue and organ function.
  • IND-enabling safety studies: These must be carried out before an investigational new drug (IND) application, the mechanism through which regulatory authorities approve use of a new candidate drug in a clinical trial. There are strict guidelines on how these studies should be carried out. Studies must be:
    • Consistent with Good Laboratory Practice (GLP).
    • Be carried out in rodents (usually rats) and one non-rodent species.
    • Include three dose groups (representing high, low and projected human doses).

Data for at least two weeks are necessary for clinical trial authorization and at least four weeks of data must be provided in final licensing applications.