Orphan diseases, affect not more than 5 in 10000 people, With some 29 million sufferers in the EU;

The EU offers the pharmaceutical industry some incentives to investigate rare illnesses. According to the General Director of LEEM, Philippe Lamoureux, European-backed research into drugs for the treatment of orphan diseases has led to 68 new medicines approved between 2000 and 2011. But there are between 6,000 and 7000 different rare diseases, so these drugs help just a fraction of sufferers.

Where does animal testing fit into the orphan drug equation? It is present in preclinical trials – as is the case with all drugs – but would it be right to ban the use of animals in research when patients have so few treatments to choose from in the first place? The Journal of Animal Ethics proposes that doctors tell patients, or their carers, the role that animals played in the development of their medicines. If sufferers of rare illnesses had access to this information, would they refuse treatment?

Stopping experimentation on animals in the EU probably wouldn’t stop European patients using drugs that have been tested on animals. The problem would simply be relocated, with testing taking place further away, in countries with less stringent regulations. Banning animal testing could also lead to a slowdown in research, as scientists consider alternative means of testing. The question remains: would sufferers of rare diseases be able to wait?

Some believe that not enough is being done to develop orphan drugs. According to work published by three Italian pharmaceutical researchers, a lack of testing on recommended animal species may have affected the investigations of 24 molecules, candidates for treatment of rare diseases. So when it comes to orphan drugs, should there be more, rather than less, research?

Sufferers of orphan diseases already face limited treatment options. Take animal experimentation out of the equation, and drug development options shrink even further.

Read the Europe 2020 strategy and the Innovation Union policy and the message from EU policymakers is clear. Europe says it needs to be in the Premier League of scientific R&D, not just because research delivers solutions that help improve our lives, but because we want to develop and produce things that have value; things people in the US, Japan, China and elsewhere will buy from us.

Rhetoric vs reality

But what is the reality behind the rhetoric? And is Europe sending mixed signals about its support for research?

Last month the European Commission adopted a new regulation on clinical trials explicitly designed to make it easier to do research in the EU.

Just days later a court in Italy ordered the temporary closure of one of Europe’s leading dog-breeding facilities.

The move followed claims by animal rights groups that the Green Hill facility, a major supplier of animals for research use, was mistreating animals. The company flatly denies this. The judge granted the campaigners ‘custody’ of the animals and effectively cast a serious doubt over the future of the company.

Seeds of doubt

This raises questions about the future of dog breeding in Europe given the prominent role that the Green Hill facility played in the research landscape here, and the likelihood that other breeders will be unnerved by the incident.

And, crucially, it sows seeds of doubt too about how European policy is evolving in this area. A number of Italian politicians joined the campaign against Green Hill, tapping into an anti-research sentiment among some sections of their electorate.  

Would the human clinical trials that Europe has vowed to attract and keep be possible without animal research?

Would fewer of us consider enrolling in a trial to test the power of a new medicine if the drug had not been through safety checks on animals first?

Some 3.8 million procedures were carried out on animals including dogs, cats, mice and monkeys last year, according to press reports.

The numbers are less important than the trend. The total figure is the highest since 1981.

[Here’s one for Europhiles: If you want a sense of how long ago that was, 1981 was the year when Roy Jenkins handed over the Presidency of the European Commission to Gaston Thorn; Greece joined the European Communities; and Bucks Fizz won the Eurovision Song Contest for the UK!]

The report was published by the UK Home Office and was met with some disappointment among animal welfare proponents. This comes after years of political commitments to reduce the number of animals used in research, refine experiments which rely on animals and, ultimately, replace animal models with viable alternatives (the 3Rs).

In light of the latest numbers from the UK, it might be tempting to claim that the ‘3Rs’ commitment is no more than a fig-leaf; an empty PR promise not reflected in the daily reality of research labs. Or maybe there are simply more research projects than before?

Digging into the data

On closer inspection of that 3.8 million headline figure, it emerges that some animals were operated on more than once so we are talking about 3.8 million procedures rather than 3.8 million animals. Large numbers nonetheless but details are important.

There’s also a matter of definition. The genetic modification of animals – which is done so that an animal carries certain genes or has particular symptoms that are to be studied – is classed as a ‘procedure’. The same is true of taking a blood sample.

In fact, the number of procedures classed as ‘significant’ was just 5% of the total.

Given the particular sensitivities about the use of primates, it’s also worth asking what animals were involved.

71% of the animals used in the UK in 2011 were mice; 15% were fish; 7% were rats and 4% were birds. 235 procedures were carried out on cats, although all of that work was aimed at improving nutrition and health in cats.

Meanwhile, there was a dramatic decrease – by 75% – in the number of new world monkeys used in research.

Inspiring progress

For all of that, the headlines generated by the report, coming as they do at a time when governments are converting the new EU directive into national law, should add extra impetus to the drive towards applying the 3Rs.

One thoughtful response to the figures came from a group of scientists who took the opportunity to suggest that European funds should be tapped to fund investment in non-animal research. In fact a lot of research of this type has been funded without much genuine progress. So rather than focusing researchers on non animal research methods, wouldn’t it be better to invest in the development of more effective research tools that would bring clear 3R benefits?

Perhaps the EU’s Horizon 2020 research and innovation funding programme has the firepower and forward-looking mandate needed to support large projects of this kind.

Maintaining momentum

So while the total number of procedures on lab animals in the UK last year was up, there might be reason to hope that the momentum generated by the report will encourage timely transposition and implementation of the EU directive – and maybe even inspire policymakers to focus on and invest further in innovative research tools which could bring us faster to non animal alternatives.

The new directive, Directive 2010/63, will come into effect at the beginning of 2013. Being new to this legislation, I wanted to get a better understanding of the impact it would have, particularly on lab animals. So I’ve tried to summarize key elements and the thinking behind the new policy.

Revising Directive 86/609
After being in use for 20 years, the 1986 directive no longer reflected all the scientific changes that have taken place, including today’s use of transgenic animals, more sophisticated science and more non-animal research methods (alternatives).  There was also no mention of appropriate care and handling of different types of animals or any enforcement of good practice.

From a research point of view, authorization of a research study varied greatly from country to country, ranging from 30 days to more than 200 days.

So in summary there was a need to adapt to new thinking and technology, to set European standards that would help to create a level playing field across Europe and enforce good management of animal care.

Key objective of Directive 2010/93
The new legislation ensures that animals are used according to certain standards, and only as a last resort only because there isn’t a viable alternative method. Researchers must always apply the 3Rs principles – the least possible distress and pain, the lowest numbers and sound justification that the animals are really necessary.

Target audience of the directive
This directive governs virtually every sector that uses animals for research and development of products such as chemical and pharmaceutical industries as well as those developing cosmetic and consumer goods. Not only does this legislation affect the researchers, it also gives legal direction to lab animal breeders and transporters of lab animals.

Key legislative changes
The biggest shift in the text appears to be the move from optional best practice, to mandatory procedures. Below are some of the key changes:

Improved legislation:

• Each research project must pass a project (ethical) review. The proposed research must prove that it’s scientifically justified, and the researcher has applied the 3Rs principle of reduction, refinement and replacement. Part of the review now includes a cost/benefit assessment; showing the benefit to the patient or consumer, versus the harm done to the animal.
• The authorization system is now mandatory however most member states had this system in place already.
• The text has become clearer about the use of alternatives where they are available.
• The use of non-human primates has been restricted to essential biomedical research only.
• Some animal welfare staff are now mentioned and the role of the veterinarian and the animal welfare officer have been strengthened. There is now a requirement to have an animal welfare body within the research organization, which provides ongoing advice about, among other things, the 3Rs principles, accommodation, care and welfare of the animals and review of procedures.

New legislation:

• Member states must perform a certain number of inspections per year, some of which are unannounced.
• There are new detailed standards on caging and housing.
• The 3Rs principles are now very clearly referenced throughout the legislation, which removes any ambiguity.
• To increase transparency, research application must now include a non-technical summary outlining the process and objective of research project in layman’s terms. If the application is approved this lay summary will be published on the Internet.

All up, the legislation is much stronger than before and includes penalties for non-compliance.

Next steps
Right now all 27 member states are in the process of translating the new directive for national implementation on 1 January 2013. Over the coming months Animal Testing Perspectives will be following the activity at national level to see how the legislation is being adopted.

Related content

Finding the right balance between animal welfare & human welfare

How did we arrive at the 3 Rs: Replacement, Reduction, Refinement?

What’s in a name? Animal research vs testing vs experimentation

In this second video, Neil goes into detail on what drove his decisions that shaped the final legislation; policy regarded by some as contradictory and by others as too pro-science.

However, Neil is made of sterner stuff and I respect his final comment in the video, “I wasn’t going to be dictated by just the popular view, I was actually going to take a view that I could stand up in [sic] my conscience and live with”.

I’d be interested to hear your views on our chat with Neil, particularly his comments on the 3Rs (Replacement, Reduction, Refinement) policy. He believes the 3Rs focuses science and industry on reducing and find alternatives to using animals in research, do you?

Related content
How did we arrive at the 3 Rs: Replacement, Reduction, Refinement?

Understanding Directive 2010/63: the new legislation governing the use of lab animals

Finding the right balance between animal welfare & human welfare

Thanks to European legislation over the past 20 years, animal experts with specialized training are required on site to provide care and manage the welfare of animals used in research. The animal welfare team work in parallel with the scientific team, looking after the animals, while the scientists focus on research.

The animal welfare officer helps facilitate research and optimize techniques for the best results, so finding the right balance for the animals. This isn’t a passive relationship with the scientists; along with strict regulation that surrounds the use of animals in research, animal welfare officers review new scientific studies before they are sent for ethical review.

Surprisingly he went on to explain that his company is actively looking for and investing in alternatives for certain research. They need further development but hoped that within 10 years or so it would be a real possibility.

However, as I’ve heard several times already, it’s the authorities, who put human safety first, are the main audience to convince in relation to alternatives. Animal research and testing is required by-law before clinical trials can take place. He admitted that even if legislation didn’t demand it, the biomedical community would still use animals, but they’d do it differently.

So from an ethical standpoint, where does a person like this stand? Doing animal research does expose a dilemma, a personal dilemma he told me; even within industry people are reluctant to use animals. They understand that to produce good vaccines, they need to go through necessary testing on animals before being testing on humans, but still no one is happy to use animals.

He went on to explain, “If we must use animals we do, but from ethical point of view, animals aren’t a perfect model of humans, they don’t mimic humans, so there are some uncertainties. It’s not 100% perfect and is has limitations.”

Discussing the perception of animal research verses the reality, the vet explained that the problem starts with the lack of visibility of animal facilities. These centres are generally closed to the public so one’s imagination simply fills in the gaps. Moreover industry has never communicated on the improvements made over the past 20 years, so naturally our perceptions are stuck in the past and is far from today’s reality.

“While there is so much emotion and extremism around the use of animals in research, it’s decreasing the opportunity to have a dialogue and transparency.
If industry could be more open, the dialogue would be much more easy.”

So in fact, as a vet he was committed to ensuring animals were used ethically in research and that his company upheld, and often exceeded, the 3R guidelines.

Also read:
What’s in a name? Animal research vs testing vs experimentation

How did we arrive at the 3 Rs: Replacement, Reduction, Refinement?

Animal welfare view

Animal rights groups on the whole object to all animal testing and many advocate that the results of the testing are unreliable, and that all experiments could be replaced with non-animal testing methods.
Many argue that scientists automatically opt to use animals in trials rather than seeking out non-animal alternatives, and that this mindset needs to change.
They campaign to modernise parts of the legislation governing animal testing arguing that it is out dated.
Science has never had to prove that animal testing works, yet there is a scientific and legal demand to prove that alternatives do work.
Animal rights groups want to see animals being regarded as sentient beings instead of tools for research.
There is also concern about the rise in use of animals in genetic manipulation and cloning.

Research view
The pharmaceutical and scientific community focus on developing new medicines that are effective in humans, and that  deliver the expected result with identified side effects before they get a licence to produce and go to market.
The scientific community argues that even though animal testing doesn’t always deliver perfect results with 100% accuracy, it’s still the only way to do invasive research to understand living systems and to provide the best possible assurance of the effects of new medicines.

Legislative view
In the new Lisbon treaty animals have been given rights as sentient beings, and it’s now a legal requirement not to use animals where there’s an alternative.
European and national legislation demands all medicines are tested in animals before they can be tested in humans.
Some medicines and vaccines must be tested on animals for every batch. These tend to be medicines that are made of, or derived from a live product – such as botox, polio vaccine etc.
The current regulation 86/609 has been revised and now provides further protection for animals. The new legislation, Directive 2010/63 will take effect in member states on 1st January 2013.

Read also:

What is animal testing exactly?

Are there any non-animal testing alternatives?