Promoting Alternative Methods
We are committed to finding new ways to refine, reduce and replace animal studies. Therefore, we are continuously developing new methods, both independently and in collaboration with other organizations.
Validating and Implementing Alternative Methods
In recent years, many new methods have been developed as an alternative to animal research. After such alternative methods are validated and accepted by regulatory authorities, they are implemented quickly at Bayer and are routinely used to replace animal studies.
Bayer was involved in the development of a phototoxicity test. It detects whether substances become toxic under UV light. This is an unwanted side effect of some drugs. The test was validated by the OECD in 2003 and is now used to replace animal testing.
The Crop Science division co-authored publications showing the redundancy of the one-year dog study in assessing human health risks for the registration of agrochemicals. A data analysis proves that in 99% of cases, there would have been no significant impact on the safe exposure levels by running the one-year dog study in addition to the 90-day dog study. As a consequence of the publications and a series of initiatives the one-year dog study was removed from test requirements for agrochemicals in Europe and USA, Canada and Australia.
These are just a few examples of innovative new methods Bayer has developed. Alternative methods always have to be discussed and accepted by the regulatory authorities. The following table lists several more validated alternative methods established at Bayer or with significant Bayer contribution:
|Short Name||Objective||Replacement Potential|
|3T3 NRU Phototoxicity Test||In vitro test for identification of the phototoxic potential of a compound||Partial replacement of in vivo studies for the investigation of potential phototoxic effects of drug candidates|
|Bovine Corneal Opacity & Permeability Assay (BCOP)||In vitro alternative to the in vivo test in the rabbit (Draize Test) for eye irritation||Tiered testing strategy, replacing in vivo studies for the identification of industrial chemicals, pesticides or drugs which might cause eye irritation or severe eye damage|
|Human Corneal Epithelium (HCE Test)||In vitro alternative to the in vivo test in the rabbit (Draize Test) for eye irritation||Tiered testing strategy, replacing in vivo studies for the identification of industrial chemicals, pesticides or drugs which might cause eye irritation or severe eye damage|
|HET-CAM||Hen’s Egg Test – Chorioallantoic Membrane as in vitro alternative to the in vivo test in the rabbit (Draize Test) for eye irritation|
|3D Human Skin Model||In vitro alternative to the in vivo test in the rabbit (Draize Test) for skin irritation and corrosivity||Replacement of in vivo studies for the identification of industrial chemicals, pesticides or drugs which might cause skin irritation or corrosion. Can be used to detect photoreactive chemicals if applied in combination with UV light|
|Mishell-Dutton Culture||In vitro alternative to immune function assays in the rat or mouse (TDAR) (conduct of the entire test, consisting of treatment and immune reaction, in vitro instead of in vivo)||Reduction of the number of animal groups which have to be treated with the test substance|
|Direct Peptide Reactivity Assay (DPRA)||In chemico assay which determines the reactivity of test items with model peptides||In chemico/in vitro test battery for identification of skin sensitizers. The in vitro integrated testing strategy will replace the in vivo skin sensitization assay|
|Phospholipidosis Assay||In vitro alternative for the identification of phospholipidosis-inducing drug candidates||Avoidance of animal testing thanks to early identification of drug candidates with unfavorable properties|
|New biomarkers for cardiotoxicity and nephrotoxicity||Earlier and more sensitive prediction of cardiac and kidney toxicity of drug candidates||Reduced burden on animals and refinement of clinicochemical diagnostics using more sensitive biomarkers|
|Integration of genotoxicity tests into repeat-dose toxicity studies (IWGT working group)||Micronucleus test and/or comet assay are incorporated into repeat-dose studies||
Reduction of animal use (no separate in vivo genotoxicity studies necessary), refinement of genotoxicity assessment taking e.g. toxicokinetic, hematological and histopathological data into consideration
Collaborations to Develop Alternative Methods
Bayer collaborates with other companies and universities to demonstrate the value of alternative methods in the context of validation and feasibility studies. This helps to establish new methods internationally. The following chart lists examples of different national and international projects in which Bayer takes part to reduce the use of animals in legally required studies.
|Project description||Coordinator||Bayer’s role|
|eTOX||Integrating chemical and toxicological data for the development of computer-based systems to predict toxicities. www.etoxproject.eu||Novartis||Co-Lead|
|eTransafe||Integration of preclinical and clinical data to analyze the predictive robustness of animal studies (Translational Safety). www.etransafe.eu||Novartis||Co-Lead|
|IPIE||Development of a database, methods and processes for better prediction of ecological risks of drugs with reduced use of animals (EcoRiskPrediction). www.i-pie.org||Bayer||Lead|
|ECETOC||The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) provides a forum for expert collaboration from world-wide industry, academia and regulatory bodies who work together to develop an agreed understanding on how the state of the science can be used to improve risk assessment by developing novel tools, guidance and frameworks. This collaboration has, together with the increased awareness of animal welfare issues, promoted the development and deployment of various (computer-based) estimation methods for regulatory assessment of chemicals. www.ecetoc.org||Bayer||Lead|
Cooperation with Authorities and Other Associations
The search for new approaches and methods that help minimize animal studies is an important part of our work. We cooperate with regulatory authorities (e.g. COST Imparas), universities (e.g. University of Nebraska) and international associations (e.g. International Life Science Institute, Crop Life International) to develop alternative methods that limit or even avoid the use of animals.
Our cooperation with the Centre for Alternatives to Animal Testing (CAAT) is another important focus of our commitment to the 3Rs. CAAT combines the innovative capacity of many different companies to find new ways to replace animal studies and reduce the number of animals in laboratories.
We use scientifically valid protocols to ensure that all studies provide relevant data without using too many animals. This approach complies with animal welfare regulations which require us to justify all use of laboratory animals.