Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines

Abstract

The COVID-19-inducing virus, SARS-CoV2, is likely to remain a threat to human health unless efficient drugs or vaccines become available. Given the extent of the current pandemic (people in over one hundred countries infected) and its disastrous effect on world economy (associated with limitations of human rights), speedy drug discovery is critical. In this situation, past investments into the development of new (animal-free) approach methods (NAM) for drug safety, efficacy, and quality evaluation can be leveraged. For this, we provide an overview of repurposing ideas to shortcut drug development times. Animal-based testing would be too lengthy, and it largely fails, when a pathogen is species-specific or if the desired drug is based on specific features of human biology. Fortunately, industry has already largely shifted to NAM, and some public funding programs have advanced the development of animal-free technologies. For instance, NAM can predict genotoxicity (a major aspect of carcinogenicity) within days, human antibodies targeting virus epitopes can be generated in molecular biology laboratories within weeks, and various human cell-based organoids are available to test virus infectivity and the biological processes controlling them. The European Medicines Agency (EMA) has formed an expert group to pave the way for the use of such approaches for accelerated drug development. This situation illustrates the importance of diversification in drug discovery strategies and clearly shows the shortcomings of an approach that invests 95% of resources into a single technology (animal experimentation) in the face of challenges that require alternative approaches.

Setting the stage for next-generation risk assessment with non-animal approaches: the EU-ToxRisk project experience

“…In this context, activities aiming to increase the international acceptance of the NAMs are crucial. This requires continued interactions amongst all relevant stakeholders groups, including industry, regulatory agencies, academia, policy-makers, and NGOs (Busquet et al 2020 ). For this reason, EU-ToxRisk provided many discussion platforms in the form of stakeholder meetings, conference sessions, and closed workshops with regulators and parallel projects.…”

COVID-19 vaccines: ethical framework concerning human challenge studies

“…New approach methods might accelerate preclinical testing [ 6 ] this approach renders unnecessary the first stages of testing of the usual procedure - in the laboratory, then on animals. However, it is very different when it comes to testing on humans, which is the most time-consuming stage.…”

“…For the discovery of a new COVID-19 vaccine, the process from the fundamental concept to the administration of the vaccine preparation to the population is a long and tedious one [ 5 ]. The purpose of vaccination is to ensure effective prevention [ 6 ]. This journey can take a long time, even decades, as the logical reasoning on the mechanisms of action of the newly designed molecule, investigates the toxicity and immunogenicity characteristics of the preparation [ 7 ].…”

Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models?

“…In the last decades, significant funding and precious time have been spent on developing animal models, despite the known species differences that make the results obtained from such models often unreliable when translated to humans. As Dr. Francois Busquet and colleagues from the Center for Alternatives to Animal Testing-Europe state for COVID-19, human-relevant approaches offer crucial advantages of speed and "much more robust and exacting data than any animal experiment could deliver" [138]. In this instance, we believe it is important to highlight that Directive 2010/63/EU on the protection of animals used for scientific purposes aims non only at reducing but at the "full replacement of procedures on live animals for scientific and educational purposes, as soon as it is scientifically possible to do so" [139].…”