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1900 - 2000: The 20th century |
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The development of a modern medicine |
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| Development sequence - roll your cursor over the R & D stages |
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Discovering new medicines |
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| Picture 31. A robot workstation for screening compounds. |
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Teams of chemists, pharmacologists and biologists search for molecules with medicinal properties. Molecular structures are altered to optimise activity and minimise unwanted side effects.
Promising medicines then pass on to the second phase of development. Phase I trials use healthy volunteers to test medicines and gather information on how the body reacts to them. This pharmacokinetic information tells researchers the best way to give the medicine and how it behaves once inside the body. Once this data is available from volunteers, an application can be made to start clinical trials in patients.
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At this pre-clinical development phase, additional tests are carried out. These include animal tests to check that the chemical compound is not poisonous and chemical tests to show that it is stable enough to be used as a medicine.
Phase II trials see the new medicine tested in a small number of patients. If it looks to have beneficial effects, the medicine will go on to phase III clinical trials that include a much larger number of patients to generate significant statistical data.
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| Placebo |
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Some clinical trials use a placebo.
In a trial the patients are randomly divided into two groups. One group is given the medicine under trial and the
other group is given a control medication. In most cases the new medicine is compared with the best available treatment
for that disease but, if no aternative exists, a placebo is used. A placebo does not contain any active ingredient.
Neither the patients nor their doctors know if they are taking the medicine or the placebo.
It is important to have a control so that any beneficial effects seen are known to be due to the medicine and not just because the patient or
doctor believe they are using something new and better than their previous treatments.
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| A massive task |
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For every new medicine that passes all the trials over 5,000 compounds
need to be screened. Each year the UK pharmaceutical
industry markets around twenty new medicines.
On average It takes an amazing eleven years
of development and £550 million
for each new medicine that reaches the patient.
A technique called high-throughput screening has automated many of the initial tests and pharmaceutical laboratories may now screen thousands of compounds per week. Research chemists can use computers to model designer molecules and using the latest equipment, large pharmaceutical companies may synthesise and screen 300,000 molecules a year.
The development of salbutamol to treat asthma is a typical example of how a medicine is designed tested and produced. You can find out more in the Asthma e-source.
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| Picture 32. Formulations for a medicine |
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| Formulating medicines |
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The formulation of a medicine is how it’s made up. For example, tablets and ointment are both types of formulation. The formulation depends on several factors including:
- how easy it is to take or use
- how quickly a medicine needs to get into the body
- where it has to work in the body
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Roll over the diagram to find out about different formulations
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| Discovery Research |
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A pharmaceutical company chooses a disease which needs treatment. The scientists investigate its causes and effects. They then look for therapeutic compounds that might treat the disease. These might be extracted from a plant or found in their database of compounds. However, these days, many new molecules are generated on a computer.
All the new molecules are screened using biological techniques or computer models. During the screening, scientists can assess whether the molecule is likely to have the desired effect and how safe it might be. As soon as a molecule looks promising, it is patented. This prevents other companies from freely using the same molecule for 20 years.
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| Preclinical development |
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The promising compounds are then made up in small quantities and studied in the laboratory. Initially, they will be tested on cell cultures. These are collections of living cells that respond as though they were part of an animal. The scientists can determine if the molecules are toxic and if they have any therapeutic effects.
Eventually, after extensive testing in the laboratory, a few molecules will prove to have the right properties. These will be tested on animals. These tests can reveal new information about the effects of the molecule in a living body. Before a new compound can be given to humans, much work has to be undertaken to determine:
- whether it is likely to be effective
- whether it is acceptably safe
- whether it is sufficiently stable
- how it is going to be absorbed and excreted by the body.
The data from the preclinical tests are used to apply for a certificate to conduct clinical trials. In the UK, this is issued by the Medicines and Healthcare Products Regulatory Agency (MRHA). Independent medical and scientific experts review the large amount of data. They have to be certain that the medicine will not cause undue harm to people who are already ill.
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| Clinical trials - phase I |
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Phase I trials. This is the first time the new substance is administered to humans; usually the trial is conducted on a small number of healthy, informed volunteers under the close supervision of a doctor. The purpose is to determine if the new compound is tolerated by the patients' bodies, and behaves in the predicted way. The initial dose of the medicine will be as low as possible, but enough to obtain the required information. |
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| Clinical trials - phase II |
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Phase II trials. These are the first tests in which the illness is actually treated. A group of approximately 200 informed patients is given the medicine. The scientists monitor their progress. They use the results to determine that the medicine works and to check that it does not produce unacceptable side effects. They will also use a control group who are given a placebo. This is to measure how much better the patients feel because they think they are being treated. This has to be taken into account when calculating the effectiveness of the real medicine |
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| Clinical trials - phase III |
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Phase III trials. Now the trial is broadened to involve many more patients - between 1000 and 3000. The group is big enough for the company to use statistics to analyse the results. If the results show that the medicine is effective and acceptably safe, the data are presented to the licensing authorities for a commercial licence. |
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| Clinical trials - phase IV |
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Phase IV trials. This is a surveillance operation once the medicine is on the market. The medicine is made available to doctors, who start prescribing it. The effects can be monitored on thousands of patients to help identify any unforeseen side effects. |
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