Author

Dr. Torben Gehring, Deputy Head of Department of in vitro Pharmacology/Toxicology Group Leader Hemocompatibility Testing

Dr. Banu Akdogan, Group Lead Genotoxicology Eurofins Medical Device Testing

Article

The publication of ISO 10993-3:2026 represents one of the most significant updates to the biological evaluation framework for medical devices in recent years. The revised standard reflects a continued evolution in how genotoxicity, carcinogenicity, reproductive toxicity, and developmental toxicity are assessed, moving beyond a predominantly testing-focused approach and placing greater emphasis on risk-based evaluation.
A central aspect of the revision is the increased use of chemical characterisation in accordance with ISO 10993-18 and toxicological risk assessment in accordance with ISO 10993-17 to support safety evaluations. Rather than relying primarily on biological testing, manufacturers are encouraged to utilise available scientific information to better understand potential patient exposure and associated toxicological risks.

Increased Reliance on Toxicological Risk Assessment

One of the most notable changes introduced in ISO 10993-3:2026 is the increased reliance on toxicological risk assessment.
The revised standard highlights the importance of scientifically evaluating extractables, leachables, and exposure information when assessing potential biological risks. This reflects a broader trend across the ISO 10993 series, where chemical characterisation and toxicological expertise play an increasingly important role in supporting biological evaluations.
For manufacturers, this means that a thorough understanding of device composition, potential chemical release, and exposure considerations becomes increasingly important when developing a biological evaluation strategy.

Integration of ISO/TR 10993-33

Another significant change is the incorporation of guidance previously contained within ISO/TR 10993-33:2015 directly into ISO 10993-3.
By integrating this guidance into the main standard, ISO 10993-3:2026 provides a more comprehensive framework for genotoxicity evaluation within a single document. This integration helps consolidate important considerations and supports a more streamlined approach to evaluating genotoxic risk.

New Guidance on Endocrine Disruptors

ISO 10993-3:2026 also introduces dedicated considerations for endocrine disruptors.
The inclusion of endocrine-active substances reflects growing awareness of the importance of understanding substances of concern that may be present within medical devices. The revised standard highlights the need to consider the potential presence and toxicological relevance of such substances as part of the overall biological evaluation process.

Dedicated Evaluation Strategies for Nanomaterials

The revised standard places greater emphasis on the evaluation of nanomaterials by recognising that conventional testing approaches may not always be suitable for characterising their genotoxic risk. Given the unique properties of materials at the nanoscale, ISO 10993-3:2026 introduces targeted recommendations to support the selection of appropriate assessment strategies and the generation of scientifically robust data. This addition helps ensure that potential risks associated with nanomaterial exposure are evaluated using methods that reflect their distinctive behaviour and biological interactions.

Expanded Focus on Developmental and Reproductive Toxicity

Developmental and Reproductive Toxicity (DART) receives increased attention within the revised standard.
Developmental toxicity is now explicitly addressed, reflecting an expanded focus on evaluating potential risks associated with patient exposure. This addition further strengthens the framework for assessing reproductive and developmental safety considerations where relevant.

Reduced Reliance on Animal Testing

ISO 10993-3:2026 further advances the ongoing shift toward alternative, science-driven assessment strategies that reduce dependence on animal testing. The standard emphasises the value of analytical chemistry, toxicological risk assessment, and exposure-based evaluations in generating the evidence needed to assess biological safety. This risk-based framework enables manufacturers to make well-justified decisions using relevant scientific data, supporting both regulatory expectations and the principles of the 3Rs (Replacement, Reduction, and Refinement).

What Does This Mean in Practice?

As these changes become integrated into biological evaluation programmes and regulatory submissions, manufacturers may benefit from reviewing existing device portfolios and assessment strategies.
Compliance with the updated expectations will increasingly depend on the quality and robustness of:

• Chemical characterisation programmes
• Extractables and leachables assessments
• Toxicological risk assessments
• Biological Evaluation Reports (BERs)
   

Early evaluation of existing documentation and supporting data may help identify potential gaps and support a smoother transition to the revised requirements.

Looking Ahead

ISO 10993-3:2026 reflects an important step in the continued evolution of biological evaluation. By strengthening the role of chemical characterisation, toxicological risk assessment, and scientific evaluation, the revised standard supports a more comprehensive risk-based approach to assessing genotoxicity, carcinogenicity, reproductive toxicity, and developmental toxicity.
As manufacturers prepare for implementation, understanding these changes and their practical implications will be an important part of maintaining effective biological evaluation programmes and supporting regulatory submissions.

At Eurofins Medical Device Testing, our multidisciplinary teams of toxicologists, chemists, and biocompatibility experts support manufacturers in navigating these evolving requirements, from analytical characterisation through to toxicological risk assessment and regulatory strategy.

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