Pre-clinical studies are an essential part of the Drug discovery process. Testing has historically been carried out on animals to assess the indications of new drugs before human testing.
However, animal testing is considered ill-suited for several reasons, including ethical issues and cost-effectiveness.
Therefore, reducing animal testing in pre-clinical studies and using alternatives are key factors to the ongoing need for rapid Drug development.
The relevance of pre-clinical studies
Pharmaceutical companies are constantly working to find cures for new and existing diseases. This is not a simple procedure and developing a new drug can take 10 to 15 years, from initial conception to EHA (European Health Association) or FDA (Food and Drug Administration) approval.
New drug development is also an expensive business, with the costs running up to millions of dollars just for one medicine or vaccine.
Pre-clinical studies allow scientists to test whether a drug can continue to be developed or needs adjustments. The advances in alternative models that have taken place over the past few years have led to a reduction in the tests being performed on animals.
The importance of the three Rs
In the past drugs were tested on animals, often causing the animals harm and discomfort, as this was the only way to see if drugs would affect a ‘live’ sample.
However, the need for animal testing has reduced as research methods become more advanced.
The 3Rs policy (Replacement, Reduction, and Refinement of animals) seeks to replace animal testing in pre-clinical studies by finding suitable alternatives for pre-clinical research, reduce the harm done to them, and refine research. This approach was developed over 50 years ago and sets quality standards in the field of animal testing within Drug development.
The 3Rs comprise these aims:
- Replace – Use a suitable alternative model to animals whenever possible.
- Reduce – Reduce the number of animals used in testing.
- Refine – Minimize the suffering of animals during research.
The general aim of the policy is to ensure that if animals must be used for pre-clinical trials then they are treated humanely. If there is an alternative model then it should be used instead.
All reputable medical researchers use the 3Rs as guidelines for using animal models in research.
In some cases, the benefits to human health outweigh the costs of using animals in medical research, which is when ‘Refinement’ should be implemented. This refers to the need to ensure that the animals are kept in good conditions and treated humanely.
The main alternatives to animal testing
Extensive trials take place before a drug can be tested on humans. As rats and mice are similar to humans in terms of genetic makeup, they are often the preferred model.
Tests need to be carried out to assess:
- Toxicity
- Efficacy
- behavior
While animal testing is known as in vivo testing, alternative models are referred to as in vitro models. The most common alternative models are:
- Zebrafish – A cost-effective vertebrate model that is easy to use and similar to the human genome
- Computer models – Simulating human diseases
- Cell cultures – Growing cells from animals and plants to replicate human cells
- Human cell cultures – Growing cells from humans, 2D, 3D, or 4D models
- Fungal models – Growing cells from fungi
- Organs on a chip – The reproduction of micro organs using computer chips
- Tissue engineering – Using human tissue
Each of these models has its benefits. The zebrafish in particular is a suitable model for pre-clinical trials as it:
- Has similar anatomy to that of humans – Including a heart, two eyes, brain, liver, kidneys, spleen, pancreas, mouth, eyes, nose, bile ducts, and intestines
- Breeds quickly (producing approximately 300 embryos every 2-3 days)
- Matures quickly – A zebrafish is an adult at 3 months and most organs have matured within 24-48 hours
- Is transparent – Facilitating development observation
- Regenerates its own organs – The heart, eyes, and cells
- Fertilizes externally – Making it easier for tests to be performed on the embryos
Zebrafish husbandry is another advantage of this alternative model, as it is not too costly to house and care for. This is a significant factor when deciding which model to use in pre-clinical trials, due to the high drug development costs.
There are many ways to reduce animal testing in pre-clinical studies and methods, and technologies are constantly developing to aid this. Choosing the right method benefits medical development, animal welfare, and pharmaceutical companies in terms of cost.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185927/
- https://www.ema.europa.eu/en/news/ema-implements-new-measures-minimise-animal-testing-during-medicines-development
- https://www.escardio.org/The-ESC/ESC-Young-Community/Scientists-of-Tomorrow/News/report-on-current-status-of-preclinical-animal-research-and-alternative-models
