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The Bologna Declaration was ratified in 1999 at the third International Conference on Alternatives to the Use of Animals in the Life Sciences, which is more than 20 years ago now. It established the need to eliminate cruelty in science as a prerequisite for the humane practice of science, and encouraged the strict application of the 3Rs (replace, reduce, and refine) in procedures involving laboratory animals.
We are now at a turning moment in biomedical research and medication discovery, as evidenced by the numerous revisions in the laws governing animal experimentation and advancements in the search for and validation of alternative models since that time.
Animal models are now helpful for understanding the pathogenic mechanisms underlying diseases and for assessing the toxicity and efficacy of drugs. The advantage of using them derives from the possibility of observing mechanisms in vivo, i.e., they allow us to discern effects on specific organs and tissues in the context of a whole organism. However, we can ask ourselves two questions:
1) Are animal models really necessary to establish the safety and efficacy of compounds, or could they be replaced by alternative models? 2) What course of action do regulatory bodies want to take in this situation?
1) Are animal models really necessary to establish the safety and efficacy of compounds, or could they be replaced by alternative models?
2) What course of action do regulatory bodies want to take in this situation?
The answers to both questions go hand in hand and have a specific name, the NAMs (New Approach Methodologies). These methodologies represent the key to the transition towards high-throughput prediction in the risk assessment of compounds on human, animal, and environmental health, reducing animal models.
These methods are mainly based on the use of in vitro (cells, tissues), non-animal, and computational models. Concern for animal welfare and the need to replace and limit the use of animals in research have led to an increase in the use of NAMs in recent years.
It should be noted that while a single NAM cannot offer enough data to predict risk in humans, a battery of different and complimentary tests can, and even exceed the predictive power of animal studies.
In Spain, as in other countries, there are alternative methods to animal experimentation that are used in scientific research and in the safety evaluation of chemical and pharmaceutical products. The most popular ones include:
There is an ongoing global commitment by government agencies, international institutions, pharmaceutical and chemical industry, academia, and animal welfare organizations to reduce and eventually eliminate the use of animals in research through the development and promotion of alternative methods.
Already in 2010, the European Union passed Directive 2010/63/EU, which establishes a common framework for the protection of animals used in research in all member states.
The EMA (European Medicines Agency) has been supporting Directive 2010/63/EU since 2011 with a number of activities. One of them is the creation of the "3Rs Working Party" (3RsWP) that promotes the use of alternative methods and assists developers of new drugs who are committed to reducing or avoiding the use of animals during the regulatory journey.
The OECD (Organization for Economic Cooperation and Development) has defined guidelines to help companies develop alternative methods for assessing the safety of chemicals that are valid for registration with ECHA (European Chemicals Agency).
In the USA, the NCTR (National Center for Toxicological Research), a division of the FDA (Food and Drug Administration) for 52 years, is dedicated to developing and validating alternative methods (in vitro and in silico) for toxicity assessment.
In this vein, the FDA Modernization 2.0 Act, signed by Biden at the end of 2022, is groundbreaking since it rescinds a federal law from 1938 that required investigational pharmaceuticals to be tested on animals before being utilized in human clinical trials. Now, 128 alternatives are approved by American agencies to reduce or replace experimental animals.
Moreover, animal testing for finished cosmetic products has been prohibited in Europe since 2004 and for its components or combinations since 2009. The complete ban was achieved in 2013, since when no cosmetics tested on animals have been marketed in the EU.
To date, animal testing is currently prohibited by law unless it is absolutely required, which is determined by an ethical commission outside of the research body.
At ZeClinics, we contribute to the reduction of animal experimentation by investing our own resources in regulatory innovation initiatives. An example of this is the DNT-DIVER project, led by the NIH, and DNT IVB, led by the OECD, to define new guidelines for the evaluation of neurotoxicity of compounds during embryonic development. These guidelines aim to complement the in vitro test battery with in vivo assays through the study of the behavior of zebrafish larvae to achieve an even more robust toxicity risk assessment. At the same time, we support transparency in animal experimentation, with our adherence to COSCE, until it is possible to renounce it.
It is crucial for society to acknowledge the advantages that animal testing has brought to human health as well as the efforts that the scientific and regulatory communities have been making for decades to find alternatives to animal testing.
Valentina Schiavone is a biomedical scientist and a quality professional in the life science industry. After a master’s degree in Molecular Biology at the University of Naples, she obtained her PhD in Cellular Biotechnologies for studies aimed to optimize bone marrow transplantation. One of these projects, led by the Centre for Genomic Regulation and in collaboration with Columbia University, culminated in the discovery of an innovative master regulator to reprogram human hematopoietic committed progenitors. In late 2018 Valentina joined the ZeClinics team in Barcelona to set up the Quality Unit. In 2022 she also obtained the title of Quality Expert for Pharma Industry by the University of Barcelona.