3 Minute 3Rs podcast: March 2022 transcript

[NC3Rs]

It’s the third Thursday of March, and you’re listening to 3 Minute 3Rs, your monthly recap of efforts to replace, reduce and refine the use of animals in research. This month, we’re highlighting three papers focusing on replacement. Let’s begin with a report on how these technologies can be applied more widely in the pharmaceutical industry.

[NA3RsC]

Complex in vitro models such as organ on a chip technology hold great promise for scientific research offering insights into efficacy and safety with significant 3Rs benefits. However, challenges remain before these technologies can be fully incorporated into drug discovery and development.

Recently the meeting report from a 2020 workshop between the FDA and pharmaceutical industry was published. The purpose of this meeting was to understand how these technologies are currently being used, identify remaining barriers, and address future pathways.

One key takeaway was consensus that there is a need to develop animal-based complex in vitro models to better understand concordance between species. Additionally, both parties agreed that for these technologies to be used in ADME, pharmacology, and safety assessment – they need qualification depending on the specific context of use. To learn more, read the full paper online.

[NC3Rs]

Next, let’s look at a new in silico tool that could pave the way for reduced reliance on animal use in regulatory toxicity testing. The STopTox tool, described in a paper published in Environmental Health Perspectives, covers six tests aimed at identifying skin and eye irritation and corrosion, and toxic effects after acute ingestion, inhalation or skin absorption. These tests can involve severe pain and distress, including intentionally causing death in some of the test animals to determine lethal doses.

While similar approaches have been developed in the past, the team behind STopTox sought to avoid reliability issues by extensively curating data from tests that followed OECD protocols. The tool correctly identified between 70 and 77% of compounds as toxic or not, as well as being validated against known toxicants not in the dataset.

The STopTox tool and all associated data are publicly available online to help scientists and regulators identify and predict toxicants without the use of animals. To learn more, find the link in the description.

And finally, strategies for replacing animal use in cardiovascular research.

[LabAnimal]

Cardiovascular diseases such as heart failure are a leading cause of mortality and disability worldwide. Although, animal models have advanced our understanding of these complex diseases, few new cardiovascular drugs have translated to the clinic. Efforts are therefore underway to develop novel experimental models with high translational value.

 In a new Consensus document published in Cardiovascular Research, the members of the European Society of Cardiology provide an overview of the different experimental models available to help cardiovascular researchers design experiments with the 3Rs in mind. This includes animal free strategies such as human induced pluripotent stem cell-derived cardiomyocytes to study atrial fibrillation or inherited cardiac diseases, as well as bioinformatic models based on large human datasets to understand cardiovascular physiology and pathophysiology. 

The authors acknowledge while cell lines are useful for novel drug screening and insights into cellular mechanisms these models presently cannot provide answers on disease mechanisms at an organ or systemic level. They also suggest solutions to increase the applicability of human stem cell-derived cell systems to enable further replacement in future cardiovascular studies.

To learn more, read the full paper online.

[NC3Rs]

That’s it for this month’s episode. 3 Minute 3Rs is brought to you each month by Lab Animal, the North American 3Rs Collaborative, and the NC3Rs. Thanks for listening, and don’t forget to listen in April for more 3Rs research.