An active substance candidate has to undergo a preclinical development programme before it can be administered to humans in clinical trials. In this programme, the substance is tested for possible harmful effects, such as whether it is toxic, causes cancer or modifies the genetic material. These tests are performed first in cell cultures and then in animal studies.
It may not be tested in humans until it has passed all the required preclinical tests. The tests in cell cultures and animals that document its harmlessness are performed in accordance with internationally accepted guidelines (ICH guidelines) which in turn are based on the 3R principles of Replace, Reduce and Refine.
The preclinical phase comprises the following studies:
- pharmacological studies,
- general toxicity studies,
- toxicokinetic and pharmacokinetic studies and
- multiple-dose toxicity studies.
Other preclinical studies are carried out in some cases depending on the specific conditions. These include an assessment of phototoxicity (when a skin response is triggered by exposure to light).