Clinical Development
Testing a new drug in man is a closely regulated process that is divided into distinct phases. The average time to complete this process was 12 years in 2002, and 9 out of 10 compounds that enter Phase I trials will fail to make it to market as drugs.
Phase 0
A recently introduced (FDA) phase where micro-dosing of candidates is used to determine distribution (PK and PD) related information in man.
Phase I
Phase I trials are the first stage of testing in human subjects. Normally, a small (20-80) group of healthy volunteers will be selected. This phase includes trials designed to assess the safety, tolerability pharmacokinetics and pharmacodynamics of a drug.
Phase II
Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients.
Phase III
Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions.
Phase IV
Phase IV trial is also known as Post Marketing Surveillance Trial. Phase IV trials involve the safety surveillance and ongoing technical support of a drug after it receives permission to be sold. In larger patient populations issues such as rare side effects or interactions with other prescribed drugs are identified.
Long term toxicology
Toxicology studies in the lead optimisation and development phases are limited to overt and fairly rapid side effects to support candidate identification and early clinical studies. Once a drug is in clinical development further toxicology studies are conducted to analyse effects in females (early studies are often males only), reproductive and developmental toxicology, longer duration toxicology/ Oncogenicity studies etc. Such studies are closely regulated by the FDA and EMEA , who determine the precise requirements of these experiments.
Registration
All countries have regulatory authorities who regulate the introduction and use of drugs. The US FDA and European EMEA authories carefully regulate every aspect of pre-clinical and clinical drug development and agreement from these authorities is required to test compounds in man and for each stage of the development process through to marketing.
Manufacturing & product development
Drug manufacture and product development processes are also regulated by the authorities to control aspects such as bulk manufacturing, stability and product use etc
