Developing a novel drug

Drug development is a long and expensive process

A drug can be developed in a whole host of different ways. The constant improvement of technology has transformed drug design over the past decade. Now, many laboratories in both universities and pharmaceutical companies make use of computers and robotics to aid in drug design. These techniques coupled with more traditional methods are becoming increasingly successful in designing novel drugs.


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One commonality between all the methods of drug design is that they are fraught with challenges. A pharmaceutical company may start with 5,000–10,000 chemical compounds as potential drug candidates. Rigorous testing will whittle this down to a single chemical compound that can then be licensed to treat patients. Developing drugs is a risky and expensive business, but the potential profits are huge.

Here, ‘Big Picture’ takes you step-by-step through how a compound in the laboratory becomes a disease-fighting drug. Option 1 explains the process of transforming initial research in a university lab into a potential drug – about a quarter of drugs approved by the FDA between 1997 and 2005 began in this way. The remaining three-quarters began in pharmaceutical or biotech companies, as explained in option 2.

STEP 1 – OPTION 1: Origins in the research lab

In universities and research institutes all over the globe, many scientists dedicate their lives to understanding how a disease affects people. By using animal models, usually mice, they are able to identify specific biochemical pathways that are altered by the disease.

A small team of scientists will study a pathway and identify a potential therapeutic target, usually a protein. To effectively target this protein, they require a detailed 3D structure. This field, known as structural biology, allows us to analyse the complex structure of the molecule and find areas that a drug could target. Their findings will be published in scientific literature.

By using the detailed structure, the scientists can use computational techniques to predict how a chemical compound might bind to the target protein. Computational techniques are cheaper than high-throughput screening but still allow the scientists to test a range of different compound structures. However, computational techniques are not without fault. The technology still lacks the ability to predict perfectly how a compound will bind. Assays can confirm binding in vitro and structural biology can show how well a compound binds.

This initial drug structure is then ready to be fine-tuned into a final structure – but this requires money and resources that the scientists probably do not have.

At this stage, the scientists may decide to set up a ‘spin-out’ company. To do this, the researchers would have to leave their normal jobs to work in a commercial environment. They would work solely on developing a drug to target the protein. They would also be required to seek investment from venture capitalists, investors who put money into high-risk projects, to fund their company.

Alternatively, the scientists could remain at their jobs and team up with a small biotech firm. At this point, it is too early for pharmaceutical companies to be interested. The biotech firm will apply for ‘seed’ funding to provide the money required for the scientists to test their agent further.

Whether they set up a spin-out company or team up with a biotech firm, the process of fine-tuning will be similar. They will use a combination of computational techniques, assays and structural biology to determine how the compound is binding. They will then change small aspects of the compound so it will act more efficiently on the target protein. At the end of all of this they will have a final structure, but there is still a very small chance that this agent will make it to market.

The biotech firm or spin-off company has gone as far as they can go. They require the monetary resources for expensive research and clinical trials that a pharmaceutical company can provide. They therefore often decide to enter a partnership with a large pharmaceutical company.

STEP 1 – OPTION 2: Origins in pharma

Pharmaceutical companies also employ large teams of scientists to carry out research of their own, similar to that of the work done in universities or research institutes. However, their work often focuses directly on potential therapeutic targets from the outset. This differs from research lab work, which might at first just aim to better understand a disease.

Importantly, pharma has access to far more resources, allowing them to carry out much larger studies. They often use a technique called automated high-throughput screening to identify initial potential compounds. This involves using robotics to test a vast amount of different compounds’ ability to bind the target protein. Once a large number of potential compounds have been identified, they will carry out further tests to reduce this library to a single compound. They may also employ computational techniques for this fine-tuning process.

STEP 2: Toxicity and animal testing

The pharmaceutical company can run many tests to find out how the agent behaves in the body, checking in animal studies for signs of toxicity and characterising further effects on the target. The company’s scientists will assess how the agent is metabolised, how long it stays in the body and where it goes.

After more chemical refinement, the agent will finally be ready to be tested in people.

STEP 3: Trials and tribulations

Once the agent has passed its toxicity tests and animal models have confirmed that it should tackle the disease in people, the phase I clinical trials will begin. A small number of healthy volunteers (usually about six) receive the drug in doses far lower than those that have proved safe in animals. The volunteers are monitored carefully for any ill effects. If the drug proves to be fine at this stage, it can advance to phase II trials.

Phase II trials involve a small group of patients – this is the first time the drug will be tested in patients. These trials ensure that the drug is safe for people with the disease to take and that it does have beneficial effects. Any drug that fails here will be an expensive loss. After phase II, the drug moves on to phase III trials. Phase III trials test the drug on a large number of patients (about 5,000) and confirm the beneficial effects. The greater the number of patients used in phase III, the more accurate the results of the study will be.

STEP 4: Convince the regulator and then the doctors

The agent will be tested in a double-blind randomised control trial, in which neither the doctor nor the patient will know who is receiving the drug and who is receiving a placebo. This ensures that any positive effects are not the result of the placebo effect but are caused by the administered drug. If these results are positive, the pharmaceutical company must then convince the regulator that the drug deserves a license.

They will submit all of the data collected during the research and clinical trials to the Medicines and Healthcare Products Regulatory Agency (MHRA). This is the body that licenses new drugs in the UK. It may request more research in response to any concerns they might have – for example, if there is an indication of any potentially harmful side-effects – before issuing a license.

Once it has gained a license, the pharmaceutical company must then convince doctors and NHS trusts that the drug is worth making available to their patients. Central to this process will be the National Institute for Health and Clinical Excellence (NICE). They will decide whether the drug offers good value for money; without their seal of approval, the drug will never make it to patients.

After NICE’s approval, the pharmaceutical company can begin marketing the drug to doctors. Unlike in the USA, pharma are not allowed to market directly to patients in the UK. Convincing doctors to prescribe the drug is the final step in the process. It may still take years for the drug to reach every patient.

About this resource

This resource was first published in ‘Drug Development’ in January 2008 and reviewed and updated in August 2014.

Medicine, Biotechnology and engineering
Drug Development
Education levels:
16–19, Continuing professional development