ISO 10993-1:2025 Revision Highlights Part 1

Reasonably Foreseeable Misuse

The November 2025 release of the revised ISO 10993-1 standard brings significant updates to biological safety evaluations of medical devices. The reversion includes addition of several new terms and definitions that are aligned with ISO 14971 risk management principles. The standard now emphasizes identifying biological effects rather than endpoints and terms such as biological harm, biological hazard, and biological risk analysis reflect more emphasis towards identification of biological consequences. Notable updates include refinement of exposure duration criteria based on contact days, clarification that the material-mediated pyrogenicity test is recommended only for devices incorporating constituents that have previously elicited a pyrogenic response (very rare) or with unknown pyrogenic potential, and inclusion of genotoxicity as an effect for consideration for devices that contact intact mucosal membranes for a prolonged period. Additionally, the ‘effects after implantation’ endpoint has been changed to ‘local effects after tissue contact’ reflecting the biological response from the potential hazards that may be associated with non-implanted devices as well as implanted. One of the major changes in this version is the requirement for including consideration of reasonably foreseeable misuse in the biological evaluation. We will outline considerations for reasonably foreseeable misuse in this post, followed by a series of blog posts highlighting some of the other significant changes introduced in the latest 10993-1 revision. Stay tuned as we break down these changes and their practical implications for manufacturers and stakeholders in the medical device industry.

What is reasonably foreseeable misuse ?

Reasonably foreseeable misuse refers to situations where a medical device is used in a manner that is not intended by the manufacturer. The definition and principles of foreseeable misuse originate from ISO 14971:2019, which covers the application of risk management to medical devices. Additionally, ISO/TR 24971:2020 provides further guidance on the application of ISO 14971. These documents establish a framework for systematically evaluating and managing risks associated with medical devices over their life cycle, including reasonably foreseeable misuse.

To what extent should manufacturers account for it? (Does this place an unreasonable burden on manufacturers?)

The key consideration in this concept is what is ‘reasonable’. Manufacturers are not required to account for every conceivable hazardous situation that could arise from device misuse. Instead, the focus should be on situations that are reasonably foreseeable and are readily predictable based on typical human behavior, user population characteristics, and the context of use. In this way, the biological evaluation process remains practical by focusing on realistic misuse scenarios rather than attempting to address every conceivable misuse.

The concept of reasonably foreseeable misuse requires manufacturers to account for how users (both laypersons or trained professionals), might inadvertently or deliberately use a device outside its indications. Such scenarios may occur due to misunderstanding, lack of knowledge, unclear instructions, or even intentional acts, all of which can lead to hazardous situations. Potential instances of misuse could be identified from the post-market surveillance data, clinical literature, off-label use or common user errors. By considering these possibilities, manufacturers can better identify and mitigate risks associated with potential misuse during the biological evaluation process.

When misuse is deliberate and not reasonably foreseeable through typical patterns of human behavior or user error, it becomes challenging for manufacturers to address these risks within the biological evaluation framework. Certain intentional misuse scenarios can be classified as abnormal use (as outlined in ISO 14971:2019). Abnormal use refers to actions that fall outside the scope of usability or the biological evaluation process. This is because the risks associated with such use cannot be effectively managed or controlled through modifications to the user interface or are outside the scope of biological evaluations.

To align with the ISO 10993-1:2025 updates, reasonably foreseeable misuse will be a key consideration that requires proactive risk assessment, realistic planning, and ensuring safety assessment beyond intended use. While manufacturers are not expected to address every possible misuse, focusing on predictable human patterns and real-world data will help make the biological evaluation more manageable. It is crucial for manufacturers and stakeholders to stay informed and adapt to the new ISO 10993 requirements, ultimately promoting safer medical devices.

MED Capabilities

MED Institute provides comprehensive biological risk assessment services to support the safety evaluation of medical devices in accordance with ISO 10993 and related regulatory requirements. Our multidisciplinary team of professionals offers expert guidance on material characterization, biological equivalence assessment, toxicological evaluation of chemical constituents, and even support in responding to submission deficiencies. MED Institute technical experts have extensive experience in developing biological evaluation plans and biological evaluation reports in compliance with global regulatory standards and based on sound scientific principles. By engaging with our team of experts, several manufacturers have designed safer products and accelerated their regulatory submissions and successful market entry.

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