Drug development Producing a new drug is an expensive and time-consuming process that is subject to extensive regulation.

Drugs are substances that exert some kind of physiological or biochemical effect on our bodies. They may be single compounds or mixtures, and their effects may be beneficial or harmful. All drugs interact with specific targets, which are usually proteins but in some cases DNA or RNA. Drugs work either by stimulating or blocking the activity of their targets.

The development of a new therapeutic drug is a complex, lengthy and expensive process. It can take from 10-15 years and over £500 000 000 to bring a drug from concept to market. This includes 2-4 years of pre-clinical development, 3-6 years of clinical development and additional time for dealing with the regulatory authorities (Figure 1).

The first stage of the process is drug discovery. In the past, many drugs have been discovered accidentally (such as penicillin) or through the analysis of folk medicines (such as quinine). Others have been designed based around the natural ligands of known drug targets. For example, albuterol is based on the hormone adrenaline and binds to the same receptor.

Today, more systematic approaches are used. High-throughput screening is used to test thousands of potential targets with thousands of diverse chemical compounds in order to identify promising lead compounds (chemical entities that interact with targets and therefore have potential as drugs). The alternative method of rational drug design involves the design and synthesis of compounds based on the known structure of either a specific target or one of its natural ligands. The results of the Human Genome Project and human pathogen genome projects provide many new potential drug targets. For this reason, target identification must be followed by target validation, which confirms the likelihood that interfering with the target protein will impact on the disease.

Drug discovery has a high attrition rate (Figure 2). High-throughput screening may identify hundreds of potential lead compounds, but many of these will be eliminated in the first round of testing either because of toxicity or lack of efficacy in cultured cells and animals. This pre-clinical development stage aims to establish how drugs are absorbed and distributed in the body, and how they are broken down and eliminated. If appropriate, there may be a process of lead optimisation where promising chemicals are modified in an attempt to alter their properties in subtle ways.

The results of pre-clinical testing are also used to determine how to best formulate the drug for its intended clinical use, e.g. as a pill, aerosol or cream.

Once the pre-clinical studies have been completed, the hundreds of lead compounds will have been whittled down to many fewer useful candidate drugs. Some of these may then be advanced to the clinical development stage, which involves testing in humans. Before this can take place, the pre-clinical studies must be submitted to the appropriate regulatory authorities. If the application is successful, the compound can be registered as an 'investigational new drug'. In the UK, the equivalent permission is a 'clinical trials exception'.

Clinical development usually consists of phase I, phase II and phase III clinical trials. These are tests on human volunteers that provide more information on drug safety and activity (see Clinical trials ). By the end of the clinical development phase, most of the investigational new drugs will have been eliminated on safety or efficacy grounds and only a very few compounds will be submitted to the regulatory authorities as a new drug application, which includes permission to market. In the UK, the equivalent permission is a market authorisation application.

After approval, pharmaceutical companies have a short period of exclusivity before patents expire and other companies can market the same drugs as generics. This time is used to recoup the massive investment required to develop and launch a new drug. However, the companies must also continue to test their drugs and monitor the feedback from healthcare professionals in order to identify undiscovered side effects, risk factors and interactions.