Drug development process
How a new drug is developed
The development of new drugs is a long and difficult process. Only one or two compounds in 10,000 tested actually make it through to being licensed treatments. A potential new medicine may be rejected at any point in the development process on safety, effectiveness or quality grounds. Overall, it may take 10-15 years for a new compoiund to get from the test tube to the medicine cabinet.
- Discovery
- Phase I
- Phase II
- Phase III
- Licensing
- NHS appraisal
- Post-marketing surveillance and Yellow Card Scheme
- New uses of a medicine
- Naming of drugs
Discovery
A fundamental first step to discovering new drugs is knowledge of the biology of a disease. This involves understanding how cell and biological processes work in health as well as what goes wrong indisease. this will reveal potential targets that a drug could act on In creasingly, research scientists have been able to understand the shape of biological molecules at the atomic level, and to use that knowledge ot design potential new drugs.
Studies in cells and animals are crucial first steps and should not be undervalued. However, many drugs that show promising results in cells in laboratories don't work in animals, and many drugs that show promising results in animals don't work in humans. The attention grabbing headlines that promise a 'cure' or 'breakthrough' are often reporting animal studies. While these studies will be adding valuable data to the body of knowledge about a condition, it's likely to be many years before this can be translated into a treatment.
Many thousands of new chemical compounds are created and tested to identify those that have potential. There is a very high drop out rate at this stage; fewer than 1 in 1,000 of all the compounds that are made ever progress to testing in humans. A new drug that shows potential will be put through a battery of laboratory and animal tests before being given a clinical trials authorisation that allows it to be tested in humans.
Phase I
The first step in testing a new drug is to determine the safety of single doses in a small number of healthy volunteers. This stage helps researchers understand some aspects of how it works and establishes the likely dose required.
Phase II
If the treatment proves to be safe, studies begin to determine the effectiveness of the drug in people with the condition to be treated. These studies may last several months or years and involve larger numbers of people, perhaps one or two hundred. The study may be:
- controlled - the drug is compared with the standard treatment or placebo (dummy treatment)
- double-blind - neither the investigators nor the participants know which treatment they are receiving
- randomised - participants will be randomly allocated to receive active treatment or placebo.
In the case of relapsing remitting MS, phase II studies typically measure the number of lesions seen in MRI scans at the beginning and end of six months of treatment.
Phase III
If a drug shows effectiveness, a larger study is conducted in hundreds of people. These clinical trials take place at different locations (multi-centre) and across several countries and may last several years. These studies allow researchers to more accurately assess the potential of the new drug in a wider range of people and compare it to existing treatments.
Phase III studies in relapsing remitting MS generally run for two years and compare the number of relapses in people taking the new drug with those taking the standard treatment or placebo.
Licensing
Data from all of these three phases is presented to the regulatory authorities (in the UK this is the MHRA - Medicines and Healthcare products Regulatory Agency or the EMA - European Medicines Agency). If the authorities are satisfied that the new medicine is effective, safe and meets manufacturing quality standards, a marketing authorisation or licence is issued.
NHS appraisal
Once a new medicine has been licensed, there may still be one final hurdle. Set up in 1999 to help eliminate post code lottery prescribing in England and Wales, NICE (National Institute for Health and Clinical Excellence) appraises certain new medicines and will look at issues such as cost effectiveness of the new treatment. In Scotland, appraisal is carried out by the SMC (Scottish Medicines Consortium).
The NHS is legally obliged to fund medicines recommended by NICE or SMC. The reverse also holds true - if NICE or SMC do not approve a new medicine, then local health authorities are not required to provide funding for it.
Post-marketing surveillance and Yellow Card Scheme
Once the newly-licensed medicine is in general use, it will be carefully monitored for safety. All medicines have a patient information leaflet (PIL), which gives instructions on how the medicine should be used, and on its side effects. Rare side effects, for example those occurring in 1 in 10,000 people may only become apparent once a medicine is in general use.
In the UK, the Yellow Card Scheme is used by doctors and members of the public to report unwanted side effects of a medicine to the MHRA. If a suspected side effect is confirmed, depending on its severity, the PIL may be amended, extra warnings may be issued or the medicine may be withdrawn.
New uses of a medicine
Clinical trials will continue after a medicine has been granted a licence. These trials aim to:
- find new treatment uses
- compare the new medicine with other treatments
- determine effectiveness in a much wider range of patients
- assess long term benefits and safety
A licence is granted for a specific use and in a particular group of people. However, once a medicine has been approved for one purpose, doctors are free to prescribe it for any other purpose that in their professional judgment is both safe and effective - this is described as off-label use.
In general use, new treatment areas may emerge or different categories of patients may be defined. In order to promote these new treatment areas, a pharmaceutical company will need to conduct further clinical trials and present new data to the regulatory authorities in order to extend the current licence.
Naming of drugs
Drug names usually start as a string of letters and numbers, a name used to identify it in the laboratory.As the drug advances through testing, it gets a generic name, or non-proprietatry name, which must be approved by the World Health Organisation. The name often reflects the drug's chemical class and use. A group of medicines that have similar actions often have similar sounding generic names. For example, penicillin, ampicillin, amoxicillin and flucloxacillin are in one group of antibiotics.
The brand name, or proprietary name, is chosen by the manufacturer, usually on the basis that it can be recognised, pronounced and remembered by health professionals and members of the public. The brand name must be unique to protect the trademark and not sound or look too much like any other drug name to avoid medical errors.