Question: What are the main stages of drug testing, from discovery to dispensary, of chemicals that can be used in medicine? How long does it take to find out if a drug is safe for large-scale use?

Lesley Pearson answered on 23 Jun 2015:

Hi Radhika, what a great question!

Drug discovery can broadly be broken down into two main areas: pre-clinical and clinical.

Preclinical describes all of the work that goes into finding a potential drug and making it the best that it can be before we put it into people. The main stages are:

Target validation:
We find a ‘target’ which is related to the disease we are interested in. This might be an enzyme that has gone wrong in a disease, or perhaps an enzyme that a bacteria needs to function. We need target validation to prove that if we affect this with a drug, it will have the effect that we are after.

Hit discovery:
We use ‘screens’ to test many hundreds of thousands of small molecules to see if any of those have the effect that we are looking for on our target-for example, we might be looking for a molecule that ‘inhibits’ the activity of an enzyme.

Hit to lead:
We work with our chemists to take ‘hits’ from our initial screens and make ‘analogues’ (difference versions which do the same thing). We also ‘profile’ the compounds so we have as much information as possible about what they do and how they do it.

Lead optimisation:
We make the hits from the screen even better: better ‘potency’-so it takes less of the molecule to have the effect; better ‘specificity’-the molecule ‘hits’ fewer other enzymes in the body, so there are less potential side effects; better ‘physicochemical’ properties-so that the drug is broken down and removed from the body in the safest manner, and also so that it can get to where it is needed.

A lot of the work that we do in the ‘pre clinical’ stages are subject to regulatory requirement-there are certain things that we need to show about a potential drug before we are allowed to see if they will work in people.

Then we move onto clinical trials. These usual involve three or four steps.

Phase 1 trials: these are usually in healthy volunteers, and these determine safety and dosage requirements.

Phase 2 trials: these are in a small number of sick patients and are used to test initial ‘efficacy’ (the drugs ability to produce a required result)

Phase 3 trials: these are larger trials which are used to test for safety and efficacy in a larger number of sick patients. This is the point at which it is decided if a drug is safe and works well enough to be given to patients.

Phase 4 trials: these are on going studies after a drug has been approved to make sure that there are no side effects that weren’t picked up in the other stages.

The whole process takes around 15 years. Phew!