Substances and routes of application

Drugs can be classified as small molecules and large molecules, often also called biologics (composed mainly of sugars, peptides/proteins, nucleic acids or combinations thereof), biosimilars (highly similar to another already approved biological drug) and vaccine candidates. See also Development of biotechnology-derived drugs with a focus on oncology drugs.

Drugs are used for many different indications:

  • Special rules exist for testing of anticancer drug candidates as explained in Preclinical development of oncology drugs, particularly if clinical trials are foreseen in terminally ill patients, who do not respond to established therapy. An overview is also provided in the table Studies needed according to ICH S9 (anticancer drug development). Anticancer drug development requires generally only a limited set of toxicological investigations and can proceed often fast, as pharmacological effects in patients are visible within weeks. Toxicological findings are often predictable, but occasionally can also be surprising
  • There are compounds, in particular drugs acting on the central nervous system (CNS) (Preclinical toxicity of CNS drugs), which behave differently when tested in healthy animals as normally used in PCS testing. Though early completion of preclinical program is generally necessary to support FIH studies, even inexistent safety ratios for PCS findings are not necessarily an impediment for development of antipsychotic drugs (a severe indication), especially as some PCS findings may not be predictive for humans or can be monitored clinically to ensure safety. Also, patient tolerance is often greater than that of test animals or volunteers

Other classifications include:

  • Complex drugs regarding combinations of active ingredients, formulations, routes of delivery and/or drug devices
  • Drug mixtures
  • Nanotherapeutics composed of nanoparticles (generally < 100 nm) in order to control biodistribution, enhance efficacy or reduce toxicity. Nanotherapeutics can consist of polymeric liposomal or nanocrystal formulations. They can comprise micelles, be protein-based, inorganic or metallic particles. Etc.
  • Prodrugs, which are administered in an inactive form and are converted into the active form by normal metabolic processes in the body
  • Radiopharmaceuticals, which are radioactive and used in diagnostics or therapy
  • Etc.

In addition, there are prescription drugs and over-the-counter (OTC) drugs. The latter can be purchased without medical prescription.

Drugs are applied by different routes, e.g. topical, oral, parenteral (e.g. intravenous, subcutaneous or intramuscular), transdermal, ocular, inhalation, etc.

Vehicles in formulations might per se or in combination with the compound induce signs, which are or may be interpreted as toxic. For not well characterized vehicles or vehicles applied by new routes etc. it is advisable to include a control group receiving the vehicle and compare it with a control group receiving a saline solution.

Other chemicals are used as cosmetics, agrochemicals or food additives. Chemicals might occur as intermediates in the production and the environment, where they are regulated e.g. by the European Chemical Agency (ECHA) in the regulations ‘Registration, Evaluation, Authorization and Restriction’ of Chemical (REACH). See also chapter on Occupational Health and Safety.