The pharmaceutical industry spends around $2.6 billion developing a single new therapeutic drug. Most candidate molecules explored during the drug discovery process will never make it to approval and widespread use. It is an understatement to say that a considerable amount of time and money is spent in the drug discovery process, which is complex and involves numerous stages, each of which can take several years to complete before progressing to the next stage.
Drug Discovery Concept. Image Credit: metamorworks/Shutterstock.com
In general, the phases of the drug discovery process are the initial research and development phase, which can last between three and six years, followed by roughly a year of pre-clinical studies, then, if successful, the candidate drug progresses to clinical trials which can last anything from a few years to over a decade, and finally, if the drug is deemed safe and effective after extensive clinical trials it then spends between one and two years in the review and approval phase.
Here, we outline each of these stages in detail.
Research and development
The research and development stage takes place over several years (usually three to six) before a potential new drug can be tested. This stage involves researching new targets for a hypothetical new drug to act on.
Research at this stage can be broad, as gaining a deeper understanding of the etiology of a disease is valuable to helping researchers identify processes or pathways that may alter the course of the disease if altered. Once a target has been selected, time is then needed to identify appropriate compounds that can act on this target without inducing toxicity in the body.
There can be tens of thousands of compounds to screen before those that act appropriately on the target can be identified. Compound screening is part of the research and development phase, it involves screening these compounds in laboratory tests, or, more recently, via virtual screening to highlight those that may be effective.
Following the screening phase, a set of roughly 10,000 compounds is usually reduced to around 250 compounds of interest that then enter the stage of preclinical testing. In this stage, the efficacy and safety of the compounds are tested before they can enter into clinical trials with humans.
There are two types of pre-clinical trials, in vivo and in vitro. In vivo studies are carried out using animal models. The type of animal used often depends on the disease being researched, however, mouse models have become popular across the board.
In vitro studies investigate candidate drugs outside of the body, usually on human cell cultures. These are favored over in vivo studies as they do not cause harm to living creatures. However, they are limited in that they can not demonstrate how the drug interacts with other organs and pathways. For researchers to conduct in vivo trials, they must provide a strong rationale for why their results could not be obtained via an in vitro study to reduce the use of animal testing.
After generally around a year of pre-clinical trials, compounds that pass safety and efficacy measures progress to clinical trials where they are tested on human participants. These trials can continue for several years but usually last between four and seven. To progress to the stage of review and approval, the candidate drug must be successful across all phases of clinical trials which can run from 0 to 4.
Phases start with a limited number of participants until enough data can be gathered to support its safety and efficacy in later phases. This prevents serious adverse events impacting larger numbers of people. Phase 1 trials usually recruit between 20 to 80 people, this grows to around 100 to 300 people in phase 2 trials and reaches thousands of people by phase 3. Around 70% of candidate drugs pass through phase 1, 33% through phase 2, and 25-30% are successful in phase 3.
Review and approval
Once a new drug is proven to be effective and safe by clinical trials it can then be submitted for approval by the regulating bodies of the countries where the drug is to be sold. Just one out of every 5,000 drug candidates is estimated to make it to the approval stage, at which point, around three-quarters of submissions are approved.
For approval to be given, researchers must demonstrate through the data collected in their clinical trials, that the benefits of taking the drug significantly outweigh the risks of taking the drug (such as the associated adverse events). At the point of approval, the total cost of developing the drug is usually around $2.6 billion and the process may have taken 10 years or more.
Each stage of the drug discovery process is vital to not only identifying and developing new therapeutic approaches but also to ensure that those taking the drugs will be safe and side effects are kept to a minimum.
- Dahlin, J., Inglese, J. and Walters, M., 2015. Mitigating risk in academic preclinical drug discovery. Nature Reviews Drug Discovery, 14(4), pp.279-294. https://www.nature.com/articles/nrd4578
- Deore, A., Dhumane, J., Wagh, R. and Sonawane, R., 2019. The Stages of Drug Discovery and Development Process. Asian Journal of Pharmaceutical Research and Development, 7(6), pp.62-67. www.researchgate.net/.../341097009_The_Stages_of_Drug_Discovery_and_Development_Process
- The Drug Development Process. The US Food and Drug Administration. Available at: www.fda.gov/.../drug-development-process