The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have recently taken measures to encourage and accelerate the development and adoption of non-animal methods in the testing and approval of new human drugs. The FDA Modernization Act 2.0, signed by President Joe Biden in late December 2022, removed the requirement for animal testing in the development of new drugs. This marks a significant step forward for the campaigners of animal alternative methods who have been advocating for the use of scientifically satisfactory alternatives. This legislation allows the FDA to promote a drug or biologic to human trials after either animal or non-animal tests.
The animal welfare organisations, such as the Center for a Humane Economy and the Animal Wellness Action, are pushing for the use of computer modelling, "organ chips," and other non-animal methods in the drug approval process. However, pro-research groups argue that non-animal technologies are still in their infancy and won't be able to replace animal models for many years. The FDA still retains discretion to require animal tests, and they don't expect the agency to change its approach anytime soon.
The animal testing era in biomedical research and drug development appears to be coming to an end with the EU and the U.S. leading the revolution. The UK also has a chance to be part of this change and maintain its position as a world leader in scientific innovations and medicine, but it needs to embrace the change and adopt new approach methodologies (NAMs). NAMs have the potential to lead the impending era of human-relevant, patient-centric research and drug discovery.
It is important to note that the change won't happen overnight, and there needs to be a framework put in place to encourage, enable, and facilitate the replacement of animal testing. The education, expertise, standardization, and validation of translational and human-relevant tools such as organ-on-chip and deep learning will play a crucial role in their acceptance and adoption by scientists and drug companies.
In conclusion, the change in regulations in the EU and the U.S. towards non-animal testing methods is a huge win for animal welfare organizations, industry, and patients in need of cures. It is a slow turning of the tide, and not a sudden change that will remake the drug approval process overnight. However, it is a step in the right direction towards modern, animal-free toxicity testing processes.
Q&A With Dr. Loryn Halliday
Today, we have the pleasure of speaking with Dr. Loryn Halliday, the Principal Scientist of PeploBio. With her PhD in immunology and pharmacology and vast research experience in the fields of oncology, microbiology, immunology, and pharmacology, she is the perfect expert to discuss the recent developments in animal testing and the implications this has for drug development and safety.
Q1: Do you believe non-animal technologies are ready to fully replace animal testing required to carry out the safety development of new drugs (and devices)?
Loryn: As we move towards a world where precision medicine provides patient-centric solutions, this offers the industry a unique opportunity to develop alternative techniques that are scientifically equivalent or go beyond current animal models to providing more clinically relevant methodologies. For some disease areas we are closer than others to fully replacing animal testing, but it is important to remember it is well-documented that animal models are imperfect predictors of human clinical response to drugs, with high translational failure, as well as being highly expensive. The majority of drugs that enter human clinical trials after animal testing fail because they are unsafe or ineffective. Non-animal technologies will enhance treatment of human disease, improve our quality of life, whilst reducing animal suffering. The change in EMA and FDA regulations are reflective of the years of work by many research groups to develop successful and scientifically sound alternatives.
Q2: What are the alternatives to animal studies?
Loryn: Globally there are many teams who are performing innovative research into New Approach Methodologies (NAMs). Organ-on-chip, organoids and human cell models and computer modelling are all examples of NAMs which have been, or, are currently undergoing development, to become successfully challenged alternatives to animal use. Results from a study of preclinical toxicity testing using a liver organ-on-chip, published in December, demonstrated that the liver-chips were able to detect liver toxicity for 87% of drugs which were historically missed by conventional animal testing. This example highlights the potential of NAMs to be a superior model to animal testing.
Q3: How far do you think we are from cutting animal testing all together?
Loryn: As the regulatory requirements until this point have relied on animal testing, there will need to be a shift in expertise and processes for toxicology testing across the pharmaceutical industry and this will take time. The continued investment in NAMs is critical for disease modelling and drug development, especially where there are no relevant animal models. For Alzheimer’s disease, a review in 2019 could not recommend any animal model which was ‘predictive for the efficacy of interventions for Alzheimer's disease’. To be able to cut animal testing further, a framework for establishing scientific confidence in NAMs is essential for the regulatory applications, along with changes in policy and funding.
Q4: What methods have you actively been using in your lab to avoid animal testing in your research.
Loryn: Avoiding animal testing is one hurdle biomedical research and drug development must overcome, but avoiding the use of animal products across research laboratory techniques is a challenge that should not be underestimated. My research focus has been around developing personalised disease models within the field of regenerative medicine, such as the ex vivo progenitor model, Blood Outgrowth Endothelial Cells. These methods tackle the use of animals in research in two ways – the model provides a patient specific clinical phenotype, representing an individual’s epigenetic makeup and therefore reduces the need for animal testing, whilst the isolation of these cells can be achieved without using animal products typically used in cell culture. In our lab, we review each project and look at whether we can actively replace animal testing and animal products to provide human-relevant results. I’m excited to see how this transition to animal-free testing set out by the EMA and FDA develops, and hope that it will inspire a change in UK regulations.