Maximising the potential of the 3Rs

The common ground across these shades is the 3Rs principles of replacement, reduction and refinement. Taking an evidence-based approach to the 3Rs brings objectivity to the debate and acts as a catalyst for change. Most importantly, it can lead to better science and business, which should be everyone’s mutual goal.

The 3Rs landscape is changing in a number of ways. For instance, there is increasing recognition that, in some areas at least, animal models may not predict what happens in humans. There are company and government pledges to reduce animal use and the international research community now has the most exciting pipeline of basic and applied 3Rs research to date. To take full advantage of this landscape we must frequently assess whether the experiments we carry out address the scientific questions we are asking.

There are three important questions that we must ask ourselves:

  • Is information from animal studies always needed?
  • Are as many animals needed to get the information as we think?
  • Are there ways to improve welfare that we have not yet considered?

We can draw from examples of cross-company collaborations led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), which thanks to the energy of passionate individuals, has catalysed change in the pharmaceutical, biotechnology and contract research fields.

Sharing information on acute toxicity studies for 70 compounds and subsequently looking at short term toxicity studies for 151 compounds has led to a reduction and refinement of the most severe type of toxicity study in drug development. Our work demonstrating that the information from conventional acute toxicity studies was not answering the questions we thought it was and was not adding value to the drug development program led directly to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) regulatory requirement for these studies to be removed in 2009. In 2007, 86% of Phase I clinical trial applications to the UK Medicines and Healthcare Products Regulatory Agency included data from acute toxicity studies; in 2012 this was reduced to 19%.

One of the reasons that acute toxicity studies are no longer needed is because more informative data is available from other studies that are already an integral part of drug development. We used the data from 151 compounds to demonstrate the potential to refine the endpoints of studies that are still carried out. For example, bodyweight loss is commonly used as an objective measure of toxicity, and our evidence-based research shows that bodyweight loss does not need to reach levels currently used in rats, dogs and primates to answer the scientific question.

This example has been used by the NC3Rs to stimulate many initiatives which have led to similar impacts on animal use in drug development. We have learned that for the 3Rs to be an effective catalyst for change we need to create the right environment for the reaction. In creating a receptive global environment for the 3Rs we have to consider three key perspectives: scientific, cultural and regulatory.

Scientifically, we need both hypothesis-driven research to feed into the 3Rs pipeline and applied research to ensure that new technologies emerging from academic laboratories are available and integrated into the marketplace. To accelerate the availability of new 3Rs technologies for scientists who work with animals we have designed a new challenge-led research initiative called CRACK IT. Scientists using animals in their research describe what their challenges are and look to the scientific community for ideas to solve them. You can find the latest Challenges at

For change to occur, all the components need to come together at the right time. At the NC3Rs we continue to create and support a culture of collaboration, partnership and celebration to increase the impact of the 3Rs. For example, we are currently accepting applications to our international 3Rs prize, which awards £20k for the most outstanding primary research paper with potential to impact on the 3Rs.

A catalyst breaks bonds and lets other bonds form. For the 3Rs to be an effective catalyst for change we may have to let go of our attachment to certain ways of doing things, embrace change and be open to new practices. As individuals, we all have the power to stimulate a 3Rs reaction, whether it be within our own organization or working alongside other organisations. Let’s make our ideas a reality.

Reposted from Kathryn’s blog on Charles River Eureka. 


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