What we really know about drug tests: advantages and disadvantages of 3R methods and animal tests

The principles of 3R (replacement, reduction and refinement) were developed over 50 years ago to conduct research on more human animals. Biomedical research requires continuous updating on solid experimental models and in this scenario 3R-based approaches can become interesting alternatives in preclinical studies.
Thursday 11th June 2020 at 15:00 PM, four researchers from different research sectors present their activity and confront each other trying to answer the following question: will we ever be able to totally replace animal tests?

Introduction: Dr. Paolo Cappella

Dr. Laura Clavillo, 3R Research Expert Consultant Cardiology Research Laborator, presents how a partial Replacement method is currently used in her laboratories to explore the neuro-immune cross-talk between nervous and cardiovascular systems. While complete Replacement was achieved only in validated methods (mainly used in toxicology, but not very common in preclinical research), technologies creating Next Generation of In-Vitro Testing Tools (partial Replacement methods) are very promising opportunities which might be validated for Fa. In conclusion, in preclinical biomedical research a global approach to 3R’s is necessary, and when animals are involved, a multidisciplinary team would be preferred, e.g. physicians for clinical questions, biologists for their knowledge of physiology, experimental models and translational aspects, vets for animal care and bioengineers for next-generation tools development.

Dr. Fabio Stellari, Senior scientist, pulmonary research, Chiesi Farmaceutici gives a practical example of how Micro CT imaging is compliance with 3R: a useful tool for lung fibrosis quantification in drug discovery. Idiopathic pulmonary fibrosis is a chronic progressive disease resulting in respiratory failure and death. There is an imperative medical need to develop new drugs, because lung transplantation remains the only modality to enhance the survival in IPF patients. Animal models play a crucial role in drug discovery process predicting clinical out-come. Micro CT as a tool to follow pulmonary fibrosis development in bleomycin mouse model. Each animal can be treated as individual subject, where disease progression and pharmacological response to treatment is longitudinally quantify. Positive correlation between micro CT parameters, histology and collagen content underlines the pivotal role of micro CT either in drug discovery or basic science.

Dr Giuliano Grignaschi, Responsible of Animal well-being, Direzione servizi per la ricerca dell’Università di Milano, presents how European legislation is implemented in our country: benefits and disadvantages. the Italian transposition of the EU Directive 63/2010 on the protection of animal used for scientific purposes has introduced in our country a series of further limitations that give rise to important limitations for researchers working in Italy compared to their colleagues in the rest of the world. Some of these limitations can have a beneficial impact on the protection of animals (i.e. OPBA vs AWB), while others are completely meaningless and may even worsen animal welfare. We urgently need to correctly transpose the EU Directive to guarantee the protection of animals, the development of complementary and alternative methods, the competitiveness of our researchers.

Dr. Silvia Scaglione, chief scientist of React4life, presents the MIVO-multi in vitro Organ device as useful and reliable tissue culture platform for in vitro testing.  MIVO is a fluid-dynamic device resembling the in vivo systemic circulation and the organ-organ fluidic connections. MIVO, already validated for intestinal permeability of molecules and medical device absorption, is also used to resemble the in vivo systemic drug transport mechanisms and test the drug efficacy against a 3D human tumor models. The results obtained up to now displayed that the MIVO platform combined with human 3D tissues can represent a novel, highly reliable and easy-to-use in vitro model for studying the passage of drugs and their effect on cellular behavior.