We often hear that there is a new treatment available or a new drug available for a specific condition. Each new treatment goes through a stringent process of monitoring to render it safe for the human body.
In this article, we are going to explore the different phases of new drug development.
The discovery of a new drug is possible either by tireless efforts of researchers around the world (either starting from scratch or modifying the chemical structure of existing drug molecules) or by unintentionally discovering new molecules, for example, the discovery of penicillin was purely by chance.
Numerous compounds get discovered every day but only a handful of them show promising results in initial data testing and get approval for further studies – this is known as the development stage.
Once a product reaches the development stage, researchers gather data to identify:
• The comparison between the effectiveness of the new product and existing similar products.
• The mode of administration – such as oral, injection, spray, or patches.
• Mode of action in the body.
• Any adverse effects.
• The dose to be given to obtaining maximum effects.
• Duration of action in the body.
• ADME – Absorption, Distribution, Metabolism, Excretion of the new drug.
• How the effect differs in people with different races, gender, or ethnicity.
• Interaction with other drugs or foods.
• Effects of the drug on the human body and how it responds to the drug.
After a drug passes the development stage, it requires further testing to assure its safety and render it suitable for treatment. The new drug goes through different researches before being tested out in humans.
The two main studies to assure its safety are:
• Research conducted in a laboratory using test tubes – In Vitro
• Research conducted in living organisms – In Vivo
Researchers have to follow certain sets of guidelines (Good Laboratory Practice – GLP) to maintain uniformity of new drug development processes. These studies do not need to be tedious but must include detailed information regarding potency and toxicity levels. The data obtained from these studies are carefully examined and a multidisciplinary team decides whether the new drug should be tested in humans or withdrawn from further testing.
Even though these studies give insights into the safety profiles of the new drug molecule, they do not substitute the need for clinical studies in the human body. Once satisfactory data is available regarding the safety of the new drug, the next stage is to conduct human trials.
Clinical trials involve a specific set of protocols that must be followed by researchers or manufacturers. They utilize information collected from the previous stages to design objectives for the clinical trials.
Based on the information available, they select:
• How many people will be needed to take part in trials
• The duration of the study
• Which group would be eligible to participate i.e. age, gender, ethnicity
• How to reduce the bias in trials
• Mode of administration of the drug
• Dose to be used for trials
• How the data will be collected
• Type of data to be collected
• Methods to review and analyze the data
Along with all the above information, manufacturers/researchers/sponsors need to seek approval from the FDA (Food and Drug Administration) to conduct clinical trials on humans. They also need to submit data collected from previous studies including, the safety profiles in animals, side effects and toxicity data, manufacturing information, any previous data available on effects on the human body, and the details of the investigator.
In clinical trials studies, the new drug molecule has to pass through three phases before it can be fully available for use.
Phase 1
In this phase, the newly identified drug is tested on a small group, usually 20 to 100 healthy volunteers, or in some cases, for example, a new treatment for terminal illness, it can be researched on volunteers already suffering from the condition.
The main aim of phase 1 clinical studies is:
• To ensure the safety and efficacy of the new drug
• Dosage profile and if it can reach the intended part of the body
• To gather evidence that it can actually offer benefits in treatment or prevention of the targeted condition or disease.
Phase 2
Once a drug passes through Phase 1, developers seek approval to do trials on a larger group of people, usually up to a few hundred. The selected volunteers do not (always) necessarily have to suffer from the disease condition the drug is being developed for.
The aim of Phase 2 clinical trials are to test:
• Clinical efficacy of the drug in the treatment
• Clinical efficacy in prevention of the condition (if volunteers don’t suffer from it)
• Establish the effective dose for treatment or prevention
This phase also establishes the efficacy of the new drug against placebo. A placebo is a substance with no active ingredients. To reduce the bias in results volunteers are not informed of the treatment they are given. This is called a “blinded study”. There is also a double-blinded study in which neither the participants nor the researchers are made aware of which group of volunteers are given a placebo or the actual drug.
Phase 3
When satisfactory results are achieved from the phase 2 study, the new drug is put forward for phase 3 trials. The FDA authenticate the results of phase 2 trials and authorize the drug to be tested on a much larger scale (in the range of a few hundred to a few thousand) of people from different backgrounds. These studies usually last between 1 – 4 years.
The main objectives of Phase 3 studies are to:
• Investigate the safety and efficacy of the new drug in a specific group of people
• Identify the optimum dosage regimen
• Identify contraindications and side-effects
• Consolidate understanding of therapeutic advantages and establish benefits versus risk studies
• Compare data with existing treatments of the targeted condition.
Once adequate data is obtained, the drug is now ready to be launched in the market. Developers obtain a marketing license to launch the product. Monitoring, however, continues after launch and is overseen by safety boards, for example, MHRA UK (Medicines and Healthcare products Regulatory Agency), Global Safety Board (GSB). The team is led by a Chief Medical Officer (CMO) and assisted by senior scientists, physicians, and chemists.
In a nutshell, the new drug development process involves three stages. First, it gets tested in a lab using computer software and human stem cells cultured in the lab (first Pre-clinical studies). After passing the first stage, it moves to the second stage where it gets tested on animals (second pre-clinical studies). Once the drug shows promising results in pre-clinical studies, it moves to human clinical trials.