In line with ICH guidelines and the REACH  regulation, research-based chemical and pharmaceutical companies are statutorily required to perform animal tests when developing new drugs in order to test the product safety of biological preparations and chemicals. Animal research provides crucial information on product efficacy and safety. Therefore, international laws require animal research to be performed prior to testing the effect of new drugs in humans, or prior to marketing chemicals on a large scale.

Animal research is only permitted if there are no recognized alternative methods available; otherwise, the alternative methods must be utilized. Animal research is, however, still unavoidable in many fields and frequently cannot be replaced by alternative testing. Because living systems are extremely complex, the entire living system of an animal must be observed and tested in order to explore, explain, or predict the course of diseases or the effects of possible treatments. All aspects of animal research are regulated by laws and regulations, which govern the housing 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 testing is approved and monitored by regulatory authorities.

For Merck KGaA, Darmstadt, Germany, animal welfare is not just an important ethical issue, but also influences the quality of test results. In order to get reliable, accurate data from our studies, we need animals that are comfortable and provided the best living conditions 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 laboratory animals, striving to continuously improve these conditions. We therefore promote the 3R principles of animal welfare:

1. Reduction of the required number of animals.
2. Refinement, e.g. to minimize the stress placed on animals before, during and after testing.
3. Replacement of animal research.

Group-wide regulations and organizational structures

Merck KGaA, Darmstadt, Germany keeps animals in its own facilities at various sites worldwide. At all our sites where animals are kept or animal tests are performed, we have appointed responsible individuals and groups (such as 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. In 2010, the biopharmaceuticals business signed the Interpharma Charter on Animal Welfare. In this charter, pharmaceutical companies commit to global Animal Welfare principles and highest possible standards in animal research worldwide.

Our Corporate Policy "Use, Care and Welfare of Laboratory Animals " describes our principles for the housing, care and feeding of laboratory animals, as well as the roles and responsibilities of the Group function Corporate Animal Science and Welfare. In this guideline, we commit ourselves to high quality and to continually improving the housing, care and feeding of our laboratory animals and expect the same from contract research organizations (CRO) as well as our business partners.

In 2014, we created the "Manual for the Group function Animal Science and Welfare". It describes the requirements for the implementation, maintenance and improvement of laboratory animal science and welfare.

Our Animal Science and Welfare unit is headed by the Corporate Animal Welfare Officer, who creates uniform animal welfare standards. This Group function initiates and conducts audits as well as institutes additional improvements to animal welfare at the company and its partners. A global laboratory animal science network, established in 2013, brings together our Animal Science and Welfare experts. The network supervises the local animal welfare units and supports specific projects and processes related to animal science and welfare (e.g. site accreditation, strategic planning concerning animal science and welfare).

Audits and site accreditation

In 2013 and 2014, our Animal Science and Welfare organization performed five audits at our own laboratory animal facilities; eight animal science and welfare audits took place at contract research organizations and animal breeders.

To demonstrate that we adhere to the highest international animal welfare standards, it is our goal to have all our laboratory animal facilities at the biopharmaceuticals business accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC ) by the end of 2015. The AAALAC accreditation factors in national laws and guidelines while also 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 ). Our two laboratory animal facilities in Darmstadt, Germany were successfully reaccredited in 2013 and 2014. The Grafing site in Germany was accredited at the beginning of 2015. The U.S. facility in Billerica, MA was AAALAC-accredited in 2012 and is preparing for reaccreditation in 2015.

Employee training

In order to ensure that animals are handled, tested, housed, fed, and cared for according to the latest standards, all employees working with laboratory animals are specially trained and receive continual advanced training. These training seminars are planned, scheduled, performed, and documented by the company's animal welfare managers in accordance with local legislation. The Group function Animal Science and Welfare supervises these measures, providing consultation and selected training as well.

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 the Federation of European Laboratory Animal Science Association,  and training provided by the Society of Laboratory Animals, the Industrial Laboratory Animal Scientists and the “Interessengemeinschaft Tierpfleger” (Community of Animal Caretakers). We also provide online training programs and classroom courses on animal welfare, the 3R principles 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 research, including in-vitro tests and computer-based methods. In November 2014, our researcher Stefan Weigt received the Hessian Animal Welfare Research Prize. He developed a method through which all possible disruptions of embryonic development due to active substances can be tested in vitro on fish embryos. This work is a major contribution to the reduction of animal research.

Over the last several years, our researchers have received multiple awards for developing alternative test methods:

• 2014: The Hessian Animal Welfare Research Prize for Alternative Methods to Replace or Reduce Animal Tests
• 2010: The IUTox Bo Holmstedt Scientists Award for Alternative Test Strategies according to the 3R Principles
• 2009: The Eurotox Gerhard Zbinden Young Scientists Award
• 2008: The Eurotox Bo Holmstedt Young Scientists Award for Alternative Test Strategies according to the 3R Principles
• 2007: The Hessian Animal Welfare Research Prize for Alternative Methods to Replace or Reduce Animal Tests
• 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
• 2005: The Eurotox Gerhard Zbinden Young Scientists Award

Within the scope of our collaboration in associations such as the European Federation of Pharmaceutical Industries and Associations (EFPIA ), the German Association of Research-based Pharmaceutical Companies (VFA), Interpharma, and the IQ 3Rs Consortium , we strive to obtain regulatory recognition for alternative testing methods that transcends national boundaries. There is a serious need for action here because animal research can only be truly reduced if a new methodology gains widespread recognition at an international level. Without international recognition, both animal research and alternative testing have to be conducted in parallel when developing pharmaceuticals intended for global distribution. Our Corporate Animal Welfare Officer represents EFPIA at the AAALAC Board of Trustees and is the chair of the IQ 3Rs Consortium in 2015.

We actively support the SET Foundation  and the 3R Foundation, both of which are dedicated to finding alternative and complementary animal testing methods with the aim of reducing animal testing. Currently, the Corporate Animal Welfare Officer is the Vice Chair of the SET board. In addition to these foundations, we are also collaborating with EFPIA to devise performance indicators that can be used to evaluate the methods for 3R improvements developed by companies.

Since 2015, Merck KGaA, Darmstadt, Germany has also been a member of the European Animal Research Association (EARA ). The EARA informs, educates and unifies audiences in support of research and facilitates an open debate on animal research.

Animal species

Before a substance is administered to an animal, we perform a careful species selection process involving computer simulation and in vitro preliminary scientific testing, as well as comparison with similar compounds. Mice and rats constitute more than 96% of the species used within the company. Other animal species (in particular non-rodents like dogs, pigs or non-human primates) are only used if specified by statutory regulations or if essential for scientific reasons. For example, regulatory authorities require pharmaceuticals in development to be safety tested in both a rodent species (e.g. rat or mouse) as well as a non-rodent species. Other guidelines (e.g. REACH) also require testing in non-rodents under certain circumstances. In this way, potential side effects can be identified with higher accuracy and included in the risk assessment. In all experiments, the safety of human beings is our top priority.

Animal species

Animal welfare practices of external partners

We procure our lab animals from special animal breeders and furthermore hire special contract research organizations to conduct animal research on our behalf. We also collaborate or partner with industry institutes and universities. Around 80% of animal research activities are conducted in-house, around 20% by leading contract institutes or partners from industry and academia. Our animal welfare policy stipulates that the same high standards that apply within Merck KGaA, Darmstadt, Germany also be applied equally to these external partners.

The company is developing its own auditing concept and performs animal science and welfare audits on external partners on a risk-based approach. In addition, within the scope of our work with Interpharma, we were closely involved in developing an audit concept for contract research institutes and animal breeders. An Interpharma audit was conducted on an animal breeder at two different sites in Germany in 2013. In 2014, Interpharma performed two more audits on animal breeders in France and Denmark. Three animal breeder sites and five CROs were audited by the company in 2013 and 2014. Generally, all sites were considered of high quality and well suited to serve as animal breeders. Only in a few specific instances did findings suggest some room for improvement. Three audits on breeder facilities in the Netherlands and the U.S. are planned for 2015.