In addition to the efforts of European Centre for the Validation of Alternative Methods (ECVAM) and other EU Validation Centers, a number of independent academic, government, and nonprofit organizations also operate in the European Union (EU) with more general 3Rs mandates. These include:
3R Research Foundation Switzerland
The Swiss 3R Research Foundation was established in 1987 as a tripartite initiative between the public sector Parliamentary Group for Animal Experimentation Questions, the Foundation for Animal-Free Research, and the corporations Novartis Pharma, Hoffman-LaRoche, and Serono Ltd. The foundation acts primarily as a funding body for 3Rs research in Switzerland, with a grants budget of approximately €400,000 per year. Since its inception, the foundation has provided more than €8.4 million in funding to roughly 100 research projects, such as:
- In vitro studies of lung cell-particulate matter interactions
- In vitro studies of skin sensitization using human monocyte-derived dendritic cells
- Short term assay for liver cell activated neurotoxic drugs
- Development of an in vitro system for the detection of estrogenic compounds
- Targeted reporter gene expression to improve and refine traditional models of tumor growth and metastasis
In addition to direct funding, the foundation also publishes periodic 3Rs information bulletins online and has developed an accredited 3Rs training course, which has become an integral element in animal user training and continuing education programs throughout Switzerland.
Doerenkamp-Zbinden Foundation
Founded in 1982 on the initiative of its namesakes, Hildegard Doerenkamp and the late Prof. Gerhard Zbinden, the Doerenkamp-Zbinden Foundation was created to promote and reward "exceptional achievements in animal protection in biomedical research." From its inception through the mid-1990s, the foundation focused primarily on reducing the suffering of animals used in experiments, awarding roughly a dozen refinement-oriented grants of up to $50,000 per year for up to two years. Additionally, the foundation has financed the Doerenkamp Chair for Innovations in Animal and Consumer Protection at the University of Erlangen in Germany to enhance the development and use of noninvasive imaging techniques in biomedical research.
More recently, the foundation has been reorganized to focus exclusively on replacement and reduction initiatives and has renamed itself the Doerenkamp-Zbinden Foundation for Animal-Free Research. Under this new mandate, a Foundation Professorship for In Vitro Methods for the Replacement of Animal Experiments has been established at the University of Konstanz in Germany. The foundation also awards an annual prize for outstanding achievement, above and beyond its ongoing grants program.
Dr Hadwen Trust for Humane Research
Established in 1970 in honor of the distinguished 19th century physician and humanitarian Walter Hadwen, the Dr Hadwen Trust aims "to advance the development and acceptance of non-animal techniques to replace animals in biomedical research." To this end, the trust conducts and funds research satisfying high ethical and scientific standards. Types of support include grants for up to three-years for postdoctoral research fellows, technicians, and research assistants, as well as occasional infrastructure grants and/or funding support for workshops, conferences, and/or publications that fulfill the trust's aims. Although the trust focuses predominantly on the application of the 3Rs in the context of fundamental and applied research, it has funded a number of projects relevant to the field of regulatory toxicology, including:
- Computer models for drug testing
- Hi-tech drug selection
- Skin allergy testing
- Human placenta and medicines
- Liver metabolism and drug development
In addition to its active research and funding programs, the trust also chairs the 3Rs advocacy coalition Focus on Alternatives which works by lobbying, facilitating access to information, educating animal researchers, and organizing workshops and meetings on specific topics of concern. The trust also has an active public awareness and outreach program through its website, ScienceRoom.org.
Dutch-Belgian Society for In Vitro Methods (INVITROM)
INVITROM is a joint initiative among academic centers in Belgium and the Netherlands whose mission is the "promotion of the development, the application and the acceptance of in vitro models in the biomedical research." Information exchange, including the organization of an annual symposium, is a key function of INVITROM. So too is fostering collaboration between research institutes, industry, and regulators in support of more rapid development and acceptance of in vitro models, paradigms, and strategies.
European Consensus Platform for Alternatives (ECOPA)
ECOPA is an EU-wide umbrella group for national "consensus platforms" comprising academic, government, industry and animal welfare stakeholders working cooperatively to advance the 3Rs in member states. The stated mission of ECOPA is "to facilitate the exchange of scientific information, expertise and experience between national consensus platforms, industry, science, animal welfare and EU and government institutions to enhance the further development and implementation of refinement, reduction and replacement in animal experimentation in Europe and worldwide." To this end, ECOPA organizes conferences and seminars, maintains an online repository of 3Rs databases and animal welfare legislation, and supports scientific and educational initiatives that are consistent with its mission.
ECOPA's membership includes consensus platforms in the following EU countries:
European Partnership for Alternative Approaches to Animal Testing (EPAA)
The EPAA was established in 2005, as a joint initiative of the European Commission (EC) and a number of companies and trade associations for the purpose of pooling knowledge and resources to accelerate the development and acceptance of 3Rs methods in regulatory toxicology. Governed by a Steering Committee comprising both EC and corporate representatives, the EPAA originally carried out its principal work through five working groups with the following mandates:
- Mapping of past and current 3Rs activities to share successful approaches and better inform the planning and prioritization of subsequent actions - included questionnaire to selected EU stakeholders to survey 3Rs research activities
- Prioritization, promotion, and implementation of future research based on the application of the 3Rs - included a workshop on new strategies for reproductive and developmental toxicity testing
- Identification, dissemination, and implementation of best practice in the 3Rs - included compiling a list of organizations promoting the 3Rs
- Implementation of the 3Rs in regulation- and decision-making - involved hosting workshops on topics such as cosmetics, pharmaceuticals, chemicals, and pesticides
- Validation and acceptance included proposing criteria for prioritization and a workshop and report on barriers to the validation and acceptance of 3Rs methods
Currently, projects of the EPAA are organized into the following three platforms:
- Science Platform: Involves the prioritization, promotion, and implementation of future research based on the application of the 3Rs; activities include workshops and/or reports on recent advances in computational and systems biology, chronic repeat dose systemic toxicity, in vitro metabolism, and in vitro ADME
- 3Rs in Regulation Platform: Involves promoting implementation of 3Rs in EU regulatory testing; activities include a review of acute systemic toxicity and alternative approaches, a workshop on the use of the consistency approach for routine release of vaccines, feasibility study for replacing the two-generation study reproductive toxicity study with a one-generation study, identification of priority areas for implementing 3Rs in regulatory testing, promoting closer collaboration of ECVAM and industry to support test method validation, and identifying and proposing strategies for overcoming barriers to validation and regulatory acceptance
- Communication & Dissemination Platform: Includes activities that promote the identification, dissemination, and implementation of best practice in the 3Rs; includes the following limited-access databases developed by the EPAA:
- In-house Review Database: inventory of alternative methods used by companies in product safety evaluations
- Research Review Database: compilation of ongoing 3Rs research projects in the EU; intended to facilitate identification of gaps in research and inform direction of future research
The EPAA hosts an annual conference in Brussels to report on its progress and provide politicians and selected stakeholders the opportunity for additional input.
Netherlands Center for Alternatives to animal use (NCA)
NCA is an academic institute within the Utrecht University Faculty of Veterinary Medicine created to act as a focal point for coordinating research and disseminating information on alternatives to animal experiments. To this end, the center works in close collaboration with the Netherlands Organization for Health Research and Development, whose Program Committee on Alternatives to Animal Experimentation determines funding priorities for 3Rs research in Holland, as well as with ECOPA's Dutch division. NCA also performs extensive educational outreach, including:
- Publication of the NCA Newsletter
- Maintenance of a Dutch database on alternatives
- Organization of scientific workshops and symposia
- Participation in national and international networks of experts
- Instruction in the subject of alternatives to animal use during laboratory animal science classes.
Nordic Information Centre for Alternative Methods (NICA)
Founded in 1998 by the Scandinavian Society for Cell Toxicology and financed largely through grants from Swedish animal welfare and 3Rs organizations, NICA aims to provide information about alternatives to animal experiments. NICA's core activities include:
- Providing online access to the Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) and MEIC monographs on time-related human lethal blood concentrations (MEMO) databases
- Establishing and maintaining a database of alternative projects in the Nordic countries
- Providing advice to members of ethical and animal care committees
Swedish Fund for Research Without Animal Experiments
The Swedish Fund for Research Without Animal Experiments is a private organization financed by public donations that "promotes the development and validation of replacement alternatives to animal experiments by awarding grants to research projects." The fund, active since 1964, is one of the first organizations in the world to award grants specifically for the replacement and reduction of animal experimentation. Recently funded projects include:
- Neurotoxic mechanisms for acute systemic toxicity studied in vitro
- Neuronal cell model for identification of mildly eye-irritating compounds
- Studies of endocrine disruptors in the human adrenocortical cell line (H295R)
- From stem cell to T cell in vitro - optimization and validation of a new method for studing immunotoxicity
- Use of human toxicity data for the evaluation of in vitro tests
The fund regularly sponsors the annual workshops of the Scandinavian Society of Cell Toxicology, and routinely awards grants for university courses on alternatives as well as for laboratory personnel training.
UK National Center for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)
The NC3Rs was established in 2004 as an offshoot of the UK Medical Research Council (MRC) Centre for Best Practice for Animals in Research, with a mandate to serve as a focal point for 3Rs and animal welfare research and related initiatives in the UK. An independent organization, financed by and accountable to a range of government, industry, and other stakeholders, the NC3Rs is principally active in the following three areas:
- Research funding: As an extension of the UK's principal funding body for health research, the MRC, a major function of the NC3Rs is the direct funding of fundamental and applied research that will advance knowledge and application of the 3Rs. With a 2006 grants budget of £1 million, the NC3Rs was able to fund a number of both large and small projects. Funding priorities for 2007 include "tissue engineering solutions for replacing animal use" and "refinement of procedures of substantial severity."
- Publications and information dissemination: The NC3Rs produces a range of publications promoting the 3Rs, including a newsletter and commissioned articles on topical issues, new technologies, and 3Rs research. The center has also developed an expansive Internet portal to provide easy access to online databases, websites, journal articles, legislation, and other reference materials.
- Forum for stakeholder interaction: Since its inception, the NC3Rs has convened an annual stakeholder meeting "to facilitate the exchange of information and ideas, to identify priorities, and to consider issues of common interest."
The NC3Rs Annual Report for 2008, Realising the Potential, highlights the achievements of the organization over the past 12 months.
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