Author

Anja Friedrich, CEO Eurofins Medical Device Testing France 

Aude Bévillard, Team Leader, Biocompatibility & Toxicology Consulting

Article

As stated in ISO 10993-1:2025, material selection and biological risk assessment are integral parts of the medical device design process. These activities shall take into account the chemical, toxicological, physical, electrical, morphological, and mechanical properties of the materials used. The selection of a raw material should be based on a well-characterized composition, consistent specifications, demonstrated biocompatibility, controlled manufacturing process, appropriate testing, and comprehensive supplier documentation. Relevant information can typically be obtained from the material data sheet (MSDS), safety data sheet (SDS), certificate of analysis (CoA), and any available biological safety or biocompatibility documentation provided by the supplier.

Special attention should be paid to CMRs (carcinogenic, mutagenic and reprotoxic substances) and endocrine-disrupting properties of raw materials to be used for medical devices that are invasive, come into direct or indirect (transport or store substances to be re/administered) contact with the human body. MDR Annex I requests to label such materials in case of concentrations that are above 0,1 % weight by weight (w/w) in the final medical device. But even with a lower weight ratio the toxicological risk to the patient must be evaluated. 

Following ISO 13485:2016/A11:2021 the suppliers must be qualified. Nevertheless, information is often limited due to proprietary issues with the suppliers. The batch-wise quality of incoming materials and components needs to be determined e.g. by chemical analysis and/or microbiological testing.

When evaluating biological safety within a Biological Evaluation Plan (BEP), a review of the scientific literature e.g. using toxicological databases is an essential component. Many materials, such as stainless steel and medical-grade polymers, have a long history of safe use in medical applications. Nevertheless, a detailed assessment of the specific material, its intended application, and the nature and duration of body contact must always be performed. 

In the event of a material or supplier change, the potential impact on biological safety must be assessed. If the assessment demonstrates that no additional biological risk has been introduced, further testing may not be necessary. However, if additional risks cannot be excluded—for example, due to insufficient information or significant changes in material composition or manufacturing processes—supplementary testing may be required. Cytotoxicity testing is often a valuable first indicator of biocompatibility, whereas chemical characterization can identify or rule out the presence of potentially toxic substances.

For decades, suppliers have frequently relied on USP Class VI testing to demonstrate the biological safety of materials. This approach traditionally included cytotoxicity testing according to USP <87> and in vivo biological reactivity studies according to USP <88>. In the revised USP chapters, <87> has been reorganized, including the removal of the agar diffusion method, introduction of the Neutral Red Uptake (NRU) Test and the incorporation of genotoxicity-related considerations. Chapter <1184> sensitization testing is integrated into <88>. Furthermore, USP <88> no longer classifies plastic materials into six classes. Instead, the focus has shifted towards in vitro test methods. 

With the revision of chapter <87> and <88> becoming official on December 1, 2026, the scope of these chapters is limited to plastic materials of construction and plastic or elastomeric components used in pharmaceutical packaging and delivery systems, as well as packaging for combination products. Implants and medical devices are no longer within the scope of these USP chapters. The informative chapter <1031> already revised in December 2024 now provides a risk-based framework for evaluating the biocompatibility of materials used in pharmaceutical packaging and delivery systems. 

To conclude, for assessments of biological safety, a comprehensive collection and review of available information, thorough supplier qualification, and a risk-based testing strategy aligned with the intended use of the device are recommended. Consistent with current regulatory expectations, such an approach should prioritize existing data and, where testing is required, follow a stepwise strategy beginning with in vitro methods. 

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