Experiments on animals are a vital part of our research and development activities. Without these experiments it would not be possible to develop new products that are safe and effective and which as a consequence can be approved by the authorities. Although valid alternatives to testing on live animals are increasingly being developed, animal experimentation and testing continue to be a necessary part of the development of pharmaceuticals and the safety assessment of Enzymes .

We want to ensure that the use of animals is kept to a minimum, that the animals are well cared for and that they are spared all unnecessary pain and distress. In 1996, we developed the Novo Nordisk Principles on Use of Animals to delineate a set of standards that must be complied with throughout the company and at the external contract research organizations with which we cooperate.

26% reduction in the number of animals used
It is an important ongoing goal for us that the number of animals used for testing and experimentation is kept to a minimum. The two main factors determining the annual total are the number and type of ongoing research projects and the development phase of each particular project. In vitro methods are used particularly in the initial screening stages of drug discovery. In the subsequent stages, studies typically start with a large number of rodents, followed by studies requiring fewer but larger animals such as pigs, dogs or primates. Animal studies are needed for both scientific and regulatory reasons because in vitro experiments cannot fully mimic the complex interplay between organs and tissues in the living mammalian organism.

In 1998, there was a 26% decrease in the number of animals used at Novo Nordisk and at contract research organizations compared to 1997. The decrease is primarily due to a reduction in behavioural pharmacology studies and biological control testing of products.

The number of surplus animals, i.e. animals that have been purchased but not used in experiments, has decreased drastically over the last few years. We attribute this positive trend to the growing awareness of animal welfare issues throughout the organization.

Raising awareness of animal welfare
Implementing the Novo Nordisk principles for use of animals and generally raising the awareness of staff involved in animal testing is a major task for our Focus Group on Animal Welfare. An initial step in the group's work has been to supplement the principles by defining responsibilities and duties, developing instructions for animal experiments, as well as providing an overview of the legislation regulating this area.

Furthermore, the focus group has set up a one-day course for staff involved in animal testing and experimentation. The course is held twice a year in Denmark and a central element is the ethical implications of animal testing.

Video on the use of animals
Our video on Novo Nordisk's use of animals, "For Whose Sake", won a Silver Screen Award in the general education category at the 31st US International Film and Video Festival in Chicago. The video is distributed upon request to the general public with schools in particular being keen viewers. To order a copy of the video, please send an e-mail to Per Fledelius (pfl@novo.dk).

Monitoring in-house compliance with our principles
During 1998 we have developed tools by which we can benchmark our bioethical performance in relation to external and internal standards. These tools will be tested in the animal welfare area in 1999.

Contract research laboratories
While 86% of all testing and experimentation on animals takes place at Novo Nordisk's own research and development facilities, some experiments are outsourced to contract research laboratories due to a lack of in-house capacity or expertise. At present collaboration has been established with approximately 40 contract research organizations in Europe, USA, South Africa, Taiwan and Japan.

Ensuring uniform standards for animal welfare

1998 target: Develop best practice guidelines for monitoring animal welfare at contract research organizations.

In order to ensure that the standards set in our principles on the use of animals are also observed at the contract research laboratories with which we cooperate, the Focus Group on Animal Welfare has prepared guidelines for monitoring animal welfare at contract research organizations. The guidelines describe the action that must be taken before a project involving external research collaboration can be initiated, during the project and finally when the project is completed. We believe that our monitoring strategy will increase awareness of animal welfare issues both at the contract research organizations and among our own researchers visiting these laboratories. The guidelines can be viewed on our website.

We have monitored 12 contract research laboratories during 1998, all with a favourable outcome. Among them was PanLabs in Taiwan, a laboratory conducting pharmacological investigations. The process and dialogue were very positive and their attitude towards animal welfare was very proactive, especially with regard to reducing the number of animals needed.

We have closely followed the initiatives taken by Huntingdon Life Sciences in the UK after the disclosure of animal abuse at their laboratories in 1997. We are satisfied that measures implemented to ensure animal welfare are fully in place and we will continue our collaboration.

International cooperation on the three Rs
Novo Nordisk is active on several international bodies focusing on the three Rs. We are for example a member of the In Vitro Testing Industrial Platform (IVTIP). Since IVTIP's establishment in 1993, we have been represented on the steering committee. The primary objectives of this forum are to monitor research results generated from EU-funded projects on in vitro testing and to provide the European Commission with input from industry on its needs for research in this area.

As a member of the European Federation of Pharmaceutical Industries Association (EFPIA), we are represented in an ad hoc group on animal research and welfare. The group is presently working on a best practice guide on dosing and blood sampling together with the European Centre for Validation of Alternative Methods (ECVAM).

Transgenic animals
Transgenic animals are animals whose hereditary traits have been permanently altered by genetic engineering techniques so that new genes, e.g. from humans, have been incorporated or certain gene sequences inactivated. Transgenic animals can be used to study the genetic basis for disease in a way that has not been possible before. Furthermore, they can be used for testing of new compounds or for the production of complex therapeutic hormones.

Novo Nordisk uses transgenic mice as models for human diseases when testing new drug candidates. They are also used to investigate adverse reactions. Approximately 2% of the animals used at Novo Nordisk in 1998 were transgenic. This is an increase of 22% compared to 1997 and is primarily due to an expansion in activities at our research facility in Seattle, USA.

We believe that transgenic animals will increasingly become an integral part of our biomedical research aimed at improving the quality of life for humans.

Cooperation with PPL Therapeutics
Novo Nordisk has 6.5% of the shares in the UK research company PPL Therapeutics PLC, a world leader in transgenic production technology. PPL Therapeutics and the Roslin Institute developed the cloned sheep Dolly.

We are working in collaboration with PPL Therapeutics on the experimental production of three pharmaceuticals: Fibrinogen to stop blood loss, Factor VII for the treatment of haemophilia and GLP-1 (Glucagon-like peptide) for diabetes therapy. In 1998, 57 sheep and 260 rabbits were used at PPL for these projects. Of the sheep, approximately 70% were transgenic and the remainder were used as donors of eggs or as surrogate mothers. Of the rabbits, half were used as donors of eggs or as surrogate mothers, 12 were transgenic and the remainder were non-transgenic littermates.

Our involvement with PPL Therapeutics is focused on the production of pharmaceuticals in transgenic animals and not on cloning techniques. We believe, however, that cloning potentially can be an important new technology, but that it needs to be assessed carefully and debated openly in public before routine use is allowed. We are in favour of the development of international guidelines to ensure that this technology is only used for ethically acceptable purposes.

View examples of replacement, reduction and refinement