Biocompatibility testing is evolving

A paradigm shift in biocompatibility testing for medical devices

04.05.2026

Biocompatibility testing is a vital part of medical device development, ensuring that materials and components are safe and compatible with the human body. Methods for the biological evaluation of medical devices have traditionally relied on in vivo animal studies but, especially since the introduction of Directive 2010/63/EU in 2010, laboratories have increasingly embraced modern in vitro methods to replace, reduce and refine (3Rs) animal use in research and testing. This shift is driven not only by ethical considerations, but also by the recognition that animal physiology is often a poor predictor of human response. In fact, in vitro biocompatibility testing often delivers faster, more accurate and more reproducible results at a fraction of the cost.

What are the challenges in biocompatibility testing?

To appreciate these challenges and explore potential solutions, it’s important to first understand the complexities of the biocompatibility testing process. Under ISO 10993 standards – which serve a central role in the biological evaluation of medical devices – instruments are categorised according to their intended clinical function and duration of contact with the body, guiding what type of tests are required (see pull-out box). Accurate sample selection, extraction and preparation are essential early steps in the process, ensuring that test materials accurately reflect the finished device and the components that will come into contact with the body. Both the materials that make up a device and the way in which a patient responds to these materials can differ considerably, leading to inevitable uncertainty and making it vital to minimise other variables to enhance the reliability and reproducibility of results.

A wide range of biocompatibility tests can be required by regulators to demonstrate the safety of new medical devices, with three core tests – cytotoxicity, irritation and sensitisation – necessary for nearly all submissions.

Cytotoxicity testing assesses whether a medical device or its extracts can cause harm to living cells.
Irritation testing determines whether a device or its extracts cause irritation to the skin, mucous or ocular tissues.
Sensitisation testing evaluates immune-mediated hypersensitivity reactions.
Genotoxicity testing identifies toxins that can alter the genetic material of cells.
Pyrogenicity testing measures the potential of a device to induce fever.