Professor Martin Kendall
Birmingham Medical School

New drugs are developed by the pharmaceutical industry. The pharmaceutical companies are huge international organisations formed by the amalgamation of smaller companies. They employ hundreds of thousands of people, have bases in most developed and many developing countries and have annual budgets of billions of pounds.

The development of a new drug is a complex, prolonged and expensive process. It takes about 15 years and may cost £100-£200 million. Furthermore, most of the compounds, which are considered as potential drugs of the future, fail to make it.

The other relevant factor is the patent life, which is 20 years. Once a new compound is produced it can be patented and becomes the property of the company for 20 years. After 20 years any company can take the compound and make it into a tablet and sell it. This is referred to as a generic preparation, as opposed to a proprietary preparation, which is made by the pharmaceutical company who do all the research and clinical trials. This explains why drugs have two names. It also explains the marketing pressure to persuade doctors to prescribe a new drug. The company that has done all the work over about 15 years has about five years to sell enough of their drug to recoup the costs of development, perhaps £150 million plus the costs of all the other compounds that did not make it. At the end of the five years i.e. when the 20-year patent life has expired any generic company can make tablets using the compound, which has already been fully investigated so their costs are extremely small. Generic preparations are therefore comparatively cheap.

Ideas for new drugs come from:

• Modifying substances that act in the body such as adrenaline.
• Hormones, vitamins, dietary supplements.
• Molecular pharmacology i.e. devising new chemicals, which have the sort of structure that has been found to work before.
• Modifications of drugs that are already available.
• Drugs from herbal remedies e.g. aspirin (willow), digoxin (foxglove), morphia (poppy).

New drugs are first assessed in animals to determine what actions they have and how toxic they are. Initially it is necessary to ensure that a modest overdose is not fatal, nor does it cause serious disease. Thereafter longer-term studies are needed to show that the drug does not damage any of the body structures, does not cause infertility or cancer and does not damage the foetus (unborn child). Once it is clear that it is not toxic in animals it is tested in healthy humans. The final and prolonged phase involves small then large clinical trials. In these the drug is tested, usually against a placebo (an inactive preparation), to show that it has a beneficial effect and does not cause unacceptable adverse effects. Nowadays the drug has to be investigated in patients with liver disease, those with kidney disease and also in the elderly.

Once all the information is available it is collected together. By now there may be half an office full of box files that are taken to the Medicines Control Agency in London (near Vauxhall tube station) if they want a British Licence, or to the European Medicines Evaluation Agency (Canary Wharf, London) if they want a European wide licence. Here a pharmacist will review the relevant material to find whether it is possible to produce a tablet containing the right amount of the right drug in the right form. A pharmacologist or toxicologist will review the animal data to ensure that the compound does not damage any part of the body and is not likely to cause cancer. A medical doctor checks the clinical trials to see if the drug has been shown to be effective and to assess its safety in man. This data is all summarised and presented to a group of experts - the Committee on Safety of Medicines - who will decide if the drug can be licensed; which means it becomes available on prescription. Once this happens the pharmaceutical company has to work very hard to persuade doctors to prescribe its ne product to enough patients to earn them enough to pay for all the development costs, plus the costs of all the failed substances and for their next therapeutic break-through.