Pre-clinical testing
Extensive testing of a drug is required before it can be trialled in patients. Pre-clinical studies involve in vitro (test tube, cells) and in vivo (animal models) experiments to understand how the drug works and how safe it is. This allows researchers and pharmaceutical companies to decide whether a drug merits further testing and development.
Once a lead compound has been identified, it is first tested for its “ADME” properties or pharmacokinetics in an animal model to ensure it is non-toxic. The term ADME stands for:
- Absorption into the bloodstream
- Distribution to the proper site of action in the body
- Metabolism that is efficient and effective
- Excretion successfully from the body
Those that make it through the initial test may be “optimised” or altered to make them more effective or safer. At this stage, the formulation and delivery mechanism (oral, injection, inhaler, topical) will also be considered. This is then followed by extensive in vitro and in vivo testing to further understand how the drug works and what the potential toxic effects are.
The discovery phase concludes when the most promising candidate drugs are deemed ready for testing in patients. After starting with thousands of compounds, there may only be between one to five drugs that are forwarded for testing in clinical trials.
However, before a clinical trial can start, an Investigational New Drug (IND) application must be filed with the appropriate regulatory authority for permission to administer a new drug to humans. In Europe and the UK, the IND application is submitted to the European Medicines Agency (EMA) or Medicines and Healthcare products Regulatory Agency (MHRA), respectively. It includes the results of pre-clinical studies, pharmacokinetic and toxicity profiles, and manufacturing information together with a detailed plan of the clinical trial to be undertaken. The regulatory body reviews the application to ensure that anyone participating in future clinical trials will not be exposed to unreasonable risks.