FRAME and the Three Rs: Yesterday, Today and Tomorrow

Michael Balls and David Morton

At one of the events to mark FRAME’s 40th anniversary, two long-standing trustees of the charity independently answered 20 questions related to FRAME’s role in the drafting and passage of the Animals (Scientific Procedures) Act 1986, and on progress made since its introduction in 1987, in terms of the reduction, refinement and replacement of animal procedures in fundamental research and testing
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Physiologically-based Pharmacokinetic Modelling for the Reduction of Animal Use in the Discovery of Novel Pharmaceuticals

Simon Thomas

The challenges of physiologically-based pharmacokinetic (PBPK) modelling and approaches to replacing the use of animals, in order to determine drug pharmacokinetics, are discussed. Reference is made to the limitations of in vivo animal studies in drug discovery. In particular, the ways in which animal studies contribute to drug attrition during the post-preclinical phase of testing are considered.
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Medical Waste Tissues — Breathing Life back into Respiratory Research

Kelly A. BéruBé

With the advent of biobanks to store human lung cells and tissues from patient donations and from the procurement of medical waste tissues, it is now possible to integrate (both spatially and temporally) cells into anatomically-correct and physiologically-functional tissues. Modern inhalation toxicology relies on human data on exposure and adverse effects, to determine the most appropriate risk assessments and mitigations for beneficial respiratory health. A point in case is the recapitulation of airway tissue, such as the bronchial epithelium, to investigate the impact of air pollution on human respiratory health. The bronchi are the first point of contact for inhaled substances that bypass defences in the upper respiratory tract. Animal models have been used to resolve such inhalation toxicology hazards. However, the access to medical waste tissues has enabled the Lung Particle Research Group to tissue-engineer the Micro-Lung™ and Metabo-Lung™ cell culture models, as alternatives to animals in basic research and in the safety testing of aerosolised consumer goods. The former model favours investigations focused on lung injury and repair mechanisms, and the latter model provides the element of metabolism, through the co-culturing of lung and liver (hepatocyte) cells. These innovations represent examples of the animal-free alternatives advocated by the 21st century toxicology paradigm, whereby human-derived cell/tissue data will lead to more accurate and more-reliable public health risk assessments and therapeutic mitigations (e.g. exposure to ambient air pollutants and adverse drug reactions) for lung disease.
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A Vision Becoming Reality

Gill Langley

Non-animal science in toxicology and health research has been progressing for decades, but
only now is it being seen widely as advanced science. The emergence of novel human biology-based tools and models, combined with legislative and regulatory change, a 21st century concept for toxicology, continuing failures in the drug pipeline, and systematic critiques of animal models, have created a pivotal moment of change. The leading edge is starting to become the norm. Humans and other animals are likely to benefit as a result.
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