Animal testing

Chemical and pharmaceutical companies are legally required to perform animal tests when developing new drugs; this is also required for the product safety of biological preparations as well as for chemicals in connection with the REACH  regulation. Animal testing provides crucial information on product efficacy and safety. Therefore, international law requires it to be performed prior to testing the effect of new drugs in humans, or prior to marketing chemicals on a large scale.

Animal testing may only be conducted if there are no recognized alternative methods available; otherwise, the alternative methods must be utilized. Animal testing is, however, still unavoidable in many fields and frequently cannot be replaced by alternative testing. All aspects of animal testing are stipulated by law and regulations, and are approved and monitored by regulatory authorities. These laws govern the treatment of laboratory animals (such as cage size, temperature, ventilation, and relative humidity), the conduct and approval of animal tests, and the reliability and expertise of all involved individuals.

Animal welfare

For Merck KGaA, Darmstadt, Germany, animal welfare is an important issue not only for ethical reasons, but also because of its influence on the quality of clinical trial results. In order to get reliable, accurate data from our studies, we need animals that are comfortable and subjected to as little stress as possible. In addition to this, we are committed to applying high, state-of-the-art quality and animal welfare standards in the housing, care and feeding of our lab animals, and we strive to continuously improve these conditions.

We promote the 3R principles of animal welfare (reduction, refinement and replacement). We therefore develop and use methods and techniques to further replace animal testing, to reduce the required number of animals, and to minimize the stress placed on them before, during and after testing.

Animal testing in pharmaceuticals and chemicals

As a pharmaceutical manufacturer, we are legally required, per government and industry regulations, to perform animal tests to prove the quality, efficacy and safety of our products prior to clinical testing. International and national laws govern the type and scope of the data to be submitted to the authorities. Animal tests are justified by the obligation to save and protect human lives and to alleviate human suffering.

For our chemicals, the EU chemicals regulation REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) that took effect in 2007 specifies that all substances manufactured in or imported to the EU must be registered and evaluated in accordance with certain requirements in order to assess their potential hazards. Depending on the amount of chemicals in question, this also includes animal testing. We minimize the number of animal tests by working with other manufacturers, importers and users in the Substance Information Exchange Forum (SIEF ) in order to share data. This allows us to avoid animal testing that is not absolutely necessary for consumer protection, or to avoid repeating animal tests that have already been conducted.

Group-wide regulations and organizational structures

Merck KGaA, Darmstadt, Germany keeps animals in its own facilities at various sites worldwide. At all of our sites where animals are kept or animal tests are performed, we have appointed responsible individuals and groups (e.g. animal care and welfare officers, institutional animal care and use committees) both on a voluntary basis as well as in response to national requirements. These units assess and assure the quality of the respective animal husbandry practices.

Our "Use, Care and Welfare of Laboratory Animals" corporate guideline, which was approved by the Executive Board in November 2011, describes our principles for the housing, care and feeding of lab animals. It also sets down the requirements we place on third parties who conduct animal testing on our behalf. In this guideline, we commit ourselves to high quality and to continually improving the housing, care and feeding of our lab animals.

Animal welfare at Merck KGaA, Darmstadt, Germany falls under the Group function Animal Science and Welfare, which has existed since January 1, 2013. The Corporate Animal Welfare Officer will create uniform animal welfare standards, conduct and/or initiate audits, and institute additional improvements to animal welfare at Merck KGaA, Darmstadt, Germany and its partners by increasing transparency throughout the Merck KGaA, Darmstadt, Germany.

As a member of Interpharma, an association of pharmaceutical companies in Switzerland, prescription medicines division has signed the Interpharma Charter on Animal Welfare.

Site accreditation

To demonstrate that we adhere to the strictest animal welfare standards, we have our laboratory animal facilities at the prescription medicines division accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International  (AAALAC Int.). In addition to taking into account the high international quality standards of the Guide for the Care and Use of Laboratory Animals from the Institute for Laboratory Animal Research  (ILAR), the AAALAC accreditation also factors in national laws and guidelines as well. In the 2011-2012 period, we received full AAALAC accreditation for our animal husbandry practices at our Non-Clinical Safety and Experimental Pharmacology units in Darmstadt (Germany) and Billerica, Massachusetts (USA). Other Merck KGaA, Darmstadt, Germany laboratory animal facilities are currently preparing to undergo the accreditation process.

Employee training

In order to ensure that animals are tested, housed, fed, and cared for according to the latest standards, all employees working with laboratory animals at Merck KGaA, Darmstadt, Germany are specially trained and receive continual advanced training. The nature and scope of this training is governed by national and international legislation as well as local requirements, and the training is monitored by the responsible regulatory authorities. In addition to this, our employees participate in external continuing education programs, such as the accredited laboratory animal science courses offered by FELASA  (the Federation of European Laboratory Animal Science Association). At the site in Darmstadt, Germany, we also offer veterinarians the opportunity to complete a three-year continuing education program to specialize in laboratory animal medicine. In addition to this, we provide online training programs and classroom courses on animal welfare, “3R” and the AAALAC accreditation standard.

Using and developing alternative methods

Whenever practical and legally feasible, Merck KGaA, Darmstadt, Germany uses alternative testing methods instead of animal testing, including in-vitro tests and computer-based methods. Over the last several years, our researchers have received multiple awards for developing alternative test methods:

• 2005: The Eurotox Gerhard Zbinden Young Scientists Award
• 2006: The German Animal Welfare Research Prize awarded by the Federal Ministry of Food, Agriculture and Consumer Protection (BMELV) for Alternative Methods to Replace or Reduce Animal Tests
• 2007: The Hessian Animal Welfare Research Prize for Alternative Methods to Replace or Reduce Animal Tests
• 2008: The Eurotox Bo Holmstedt Young Scientists Award for Alternative Test Strategies according to the 3R Principles
• 2009: The Eurotox Gerhard Zbinden Young Scientists Award
• 2010: The IUTox Bo Holmstedt Scientists Award for Alternative Test Strategies according to the 3R Principles

Within the scope of our collaboration in associations such as EFPIA, VFA, Interpharma, and the 3R IQ Consortium, we are striving to obtain regulatory recognition for alternative testing methods that transcends national boundaries. There is a serious need for action here because animal testing can only be truly reduced if a new methodology gains widespread recognition at an international level. Without international recognition, both animal testing and alternative testing have to be conducted when developing pharmaceuticals intended for global distribution.

Through our work with the German Chemical Industry Association (VCI) and the German Association of Research-based Pharmaceutical Companies (VFA), we actively support the SET Foundation, and we support the 3R Foundation through our work with Interpharma. Both foundations are dedicated to finding alternative and complementary animal testing methods. We are furthermore collaborating with the European Federation of Pharmaceutical Industries and Associations (EFPIA) to devise performance indicators that can be used to evaluate the methods for 3R improvements that companies develop.

Species

Mice and rats constitute 99% of the laboratory animals used within the Merck KGaA, Darmstadt, Germany. Other animal species are only used if mandated by statutory regulations and/or if preliminary scientific testing and experience shows the results from experiments on rats and mice to be insufficiently robust. Other animal species may also be used if preliminary scientific testing and experience indicates that the results must be backed up by testing on non-rodent species as well. Statutory regulations require pharmaceuticals in development to be safety tested both on a rodent species (rat or mouse) as well as on a non-rodent species (dog, pig or monkey). In this way, potential side effects can be identified and included in the risk assessment of a substance prior to first-in-man use. In all experiments, the safety of human beings is our top priority.

Animal welfare at external partners

We procure our lab animals from special animal breeders and furthermore hire special contract research organizations to conduct animal testing on our behalf; we also collaborate or partner with industry institutes and universities. Our animal welfare policy stipulates that the same high standards that apply within Merck KGaA, Darmstadt, Germany also apply to these external partners as well. Within the scope of our work with Interpharma during the 2011-2012 period, we helped develop an audit concept for such contract institutes. An Interpharma audit has already been conducted on an animal breeder at two different sites in Germany and found the animal husbandry practices there to be of good quality.