Animal testing and medical devices: where do we stand?

Animals have always been used in scientific and medical research to ensure that pharmaceutical products and medical devices are safe and effective before their use in humans. However, animal testing raises many ethical questions and is open to public debate.

In this context, the 3Rs principle (Replacement, Reduction and Refinement) has been established and lays the foundation for an ethical and a more humane animal research. The 3Rs principle encourages alternatives to animal testing while preserving scientific quality and improving animal welfare when the use of animals cannot be avoided.

The 3Rs stand for:

• Replacement of the use of animals with new approach methodologies (NAMs) using non-animal methods when possible. These alternative methods include in chemico assays, in vitro assays (cell culture, 3D cell cultures, organ-on-chips) and computer modelling (in silico models, i.e. structure activity relationship, Quantitative structure–activity relationship (QSAR) models, read-across),
• Reduction of the number of tested animals to a minimum while maintaining scientifically valid results,
• Refinement of practices to minimize the suffering and the stress of tested animals and improving their welfare when used for regulatory purposes.

In 2010, the European Parliament and Council published the directive 2010/63/EU regarding the protection of animals used for scientific purposes. It requires to integrate the 3Rs and welfare standards for the treatment of animals in all aspects of the development, manufacture and testing of products. The medical device European Regulation 2017/745/EU supports the implementation of the 3Rs for animal experimentation laid down in the Directive 2010/63/EU.

According to ISO 10993-1 standard, animal testing should only be carried out if the available scientific data and in vitro studies do not provide sufficient information to address the safety of the medical device. Moreover, the ISO 10993-2 standard specifies the minimum requirements to be satisfied to ensure and demonstrate that when animal testing is required, proper provision has been made for the welfare of tested animals.

In line with the 3Rs principle, alternative methods to animal testing are being developed. In vitro tests for genotoxicity evaluation are already acknowledged and mentioned in the associated standard (ISO 10993-3). For medical devices, the in vitro skin irritation assay with reconstructed human epidermis models has been adapted and validated for the testing of extracts per ISO 10993-23. The standard states that preference should be given to in vitro tests before considering animal testing or human patch test.

In vitro and in chemico assays have been developed for cosmetics and chemical substances for other biological endpoints, such as skin sensitization. However, these assays have yet to be adapted and validated for medical devices testing.

Several roadmaps have recently been developed (e.g., US EPA, EFSA) to support the implementation of NAMs for a full replacement of animal testing for chemicals. Currently, only a few toxicological endpoints can be fully assessed with non-animal methods to support classification and labelling (CLP) or to conclude on (no) hazard: skin sensitization, skin and eye irritation and (partially) genotoxicity. For the more complex toxicological endpoints, such as repeated dose toxicity, reproductive toxicity or carcinogenicity, the mandatory evaluation requirements still rely on animal testing. The need to combine several approaches to assess these more complex endpoints rather than imagine one-to-one replacement is more and more accepted and understood. Several initiatives are exploring opportunities to fulfil standard information requirements through a combination of approaches, including the use of cell transformation assays (CTAs), QSARs, toxicokinetics, and other in vitro assays and computational tools.

Undoubtedly, a better understanding of the underlying toxicological effects is needed to replace the animal testing with approaches based solely on mechanistic information from in silico/in vitro systems.

Our intervention

Efor Group provides guidance in the implementation of the ISO 10993-2 standard and the selection of in vitro models adapted for testing on medical devices.

Our team of experts is also trained in the selection of test samples, the follow-up of tests and the management of any non-conformities related to the assays. Audits of service provider laboratories may also be offered.

Moreover, our team expertise remains up-to-date thanks to a thorough watch on latest state-of-the-art, methods and standards updates. 

Our technical management teams are available to assist you in your projects and can be contacted at onedt@efor-group.com