Lord Dowding Fund for humane research


National Antivisection Society

LDF urges the European Medicines Agency to prioritise non-animal testing methods

1 June 2011

On 17th March 2011 the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) published a concept paper outlining the intention to replace their previous statement on animal testing for medicinal products.

The EMA are responsible for scientifically evaluating medicines developed by pharmaceutical companies for use in the EU. A concept paper, which is a public document, conveys the need to discuss specific issues, with a view to laying down the foundation of future guidelines.

“Replacement of Animal Studies by in vitro Models” was adopted by CHMP in February 1997 and addresses the possibility of replacing animal test methods with in vitro methods for the development of medicinal products.

Acknowledging that there has been progression on the subject since this time, the concept paper outlines the need for guidance on the three Rs; Replacement, Reduction and Refinement, in this area. The discussion looks at the need to thoroughly revise the document “in order to take into account scientific and legislative progress and to formulate guidance on when and how 3R alternatives … can be considered for regulatory acceptance”.

Recent legislative progress includes the newly revised Directive 2010/63/EU, which places a strong emphasis on the three Rs and particularly on replacement. It states that “the final goal of full replacement of procedures on live animals for scientific and educational purposes as soon as it is scientifically possible to do so”.

The Lord Dowding Fund and Animal Defenders International’s written comments on the concept paper outline the essential elements which must to be included in the guidelines to ensure that the CHMP position is in accordance with current scientific and legislative progress. The LDF emphasise that replacement of animals must remain a priority above reduction and refinement alternatives. Replacement is the only technique which obviates the use of animals; therefore this is the only method which avoids the uncertainty created by species differences. Non-animal methods are increasingly being seen as the future for toxicity testing due to issues such as adverse drug reactions and drug development failures which follow safety and efficacy testing in animals.

Additionally it is noted by the LDF that the current method of validating non-animal techniques has problems which must be addressed. For example the current validation process involves the comparison of data from new techniques to data gathered from in vivo animal experiments. However, “the majority of these traditional tests themselves were never validated”.

In the U.S.A., the National Research Council recently revised toxicity testing programme proposes that “substances known to cause and substances known not to cause the effect in humans would be used as the reference agents for positive and negative predictivity”. This makes sense – to validate a new method using animal models is not a rational approach when the model itself relates to human cells.

Another important note is for the proposals to consider all possible replacement methods for animal testing of medicinal products, of which there are many. Although the original 1997 position statement and concept paper generally discuss in vitro methods, these in vitro techniques now vary greatly and include a number of variations such as high throughput screening and toxicogenomics. The existence of other replacement methods must also be acknowledged, such as microdosing and in silico techniques.

Once the CHMP has received general comments on their concept paper, a draft guideline will be issued which will also be open to consultation. Needless to say, this will provide LDF with a further opportunity to communicate the scientific advantages, and therefore the advantages for human health, of using advanced non-animal techniques for the testing of medicinal products.

© National Anti-Vivisection Society