📘 INTRODUCTION
ISO 10993-1:2025 (6th edition), published on November 18, 2025, is one of the key foundations for the biological evaluation of medical devices. It sets out the general principles for assessing the biological safety of materials and devices that come into direct or indirect contact with the human body.
This version succeeds the 2018 edition and introduces several strategic changes for manufacturers, notified bodies, and testing laboratories.
🎯 Scope and Regulatory Context
The standard applies to all medical devices whenever contact with the human body is intended or reasonably foreseeable.
It falls within the regulatory framework of Regulation (EU) 2017/745, under which biological evaluation is an essential component of the general safety and performance requirements.
🔍 Key changes introduced in the 2025 edition
1️⃣ Enhanced integration of risk management (ISO 14971)
Biological assessment must now be fully integrated into the overall risk management process, including a systematic analysis of biological hazards, hazardous situations, potential harm, and control measures.
The 2025 version also specifies that manufacturers must ensure that individuals involved in the biological assessment possess the necessary skills and expertise, particularly in toxicology, risk assessment, and an understanding of materials.
➡️ Impact: Manufacturers will need to revise their biological evaluation processes to align them with a risk management approach.
2️⃣ ASSESSMENT OF REASONABLY FORESEEABLE MISUSE
The 2025 edition explicitly introduces the need to consider reasonably foreseeable misuse (beyond the intended use) as part of the biological assessment.
Up until the previous version, the assessment focused primarily on the intended use of the device as defined in the instructions for use. With version 2025, the intended use is no longer sufficient; scenarios of misuse must be identified and analyzed.
➡️ Impact: The biological assessment plan must now define not only the intended use but also plausible misuse scenarios, and assess the impact of these scenarios on exposure, tissue contact, or even the duration of exposure.
3️⃣ New categorization of contacts and exposure durations
Standard 2025 revises the device classification structure by replacing the previous single table (Table A.1) with four separate tables:
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Contact with intact skin.
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Contact with intact mucous membranes.
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Contact with damaged skin or mucous membranes, or internal tissues other than circulating blood.
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Contact with circulating blood.
The general duration categories (“ <: 24 hours,” “ >: 24 hours to 30 days,” “ >: 30 days”) remain, but the method for determining them now includes the concepts of “total duration of exposure,” “daily contact,” and “intermittent contact.”
The term “transient” is replaced by “very brief contact” for exposures lasting less than 1 minute. Bioaccumulation must be taken into account if a chemical component is known to accumulate, as this could result in a device being classified as “long-term.”
➡️ Impact: When drafting the biological assessment plan, the contact category must be clearly determined based on the exposure scenario. It will be essential to clearly justify the selected exposure scenario (duration, frequency, normal use, or misuse) and to analyze the possibility of multiple or prolonged exposures.
4️⃣ Chemical characterization and reduction of in vivo testing
Physicochemical data (materials, extractables/leachables, manufacturing processes) must be incorporated to identify biological hazards, hazardous situations, and adverse effects.
One of the key points of the 2025 edition is the increased emphasis on animal welfare in the context of biological testing. The standard encourages the application of the “3Rs” principle when it is determined that alternative methods (in vitro, in silico, physicochemical characterization) can provide reasonable equivalence to animal testing. Thus, before resorting to in vivo testing, the standard calls for documenting the justification for their necessity—or even avoiding them altogether if sufficient data are available.
➡️ When drafting the biological assessment plan, include a section dedicated to chemical/physical characterization; document any gaps, the rationale for not conducting certain tests, and the impact on the biological risk assessment
5️⃣ BIOLOGICAL EQUIVALENCE
ISO 10993-1:2025 strengthens and clarifies the approach to biological equivalence. It is no longer based solely on the similarity of materials, manufacturing processes, or conditions of use, but on demonstrating that a device does not introduce any new or increased biological risk compared to a relevant comparator. The standard now requires a structured gap analysis in the BEP, based on available chemical, material, physical, and contact data, in accordance with the spirit of ISO 10993-18. If equivalence is justified, no additional testing, including in vivo testing, is required.
➡️ Opportunity to reduce or avoid additional testing: conduct a more rigorous gap analysis and provide stronger supporting documentation in the BEP and BER.
6️⃣ Structured documentation: BEP and BER
The 2025 version of ISO 10993-1 significantly strengthens the documentation requirements, particularly regarding the Biological Evaluation Plan (BEP) and the Biological Evaluation Report (BER). These two documents become the cornerstones for demonstrating the biological safety of a medical device throughout its lifecycle.
📄 The BEP must clearly define the context of use, the duration of exposure, the type of contact, and the reasonably foreseeable scenarios of intended and unintended use. It must document the identified biological hazards, existing data, data gaps, acceptability criteria, and tests that are necessary or not justified. It must include a comprehensive justification for alternative approaches (in vitro, in silico), particularly in accordance with the 3Rs principles. It must specify the skills and expertise involved in the assessment.
📄 The BER is the final document that consolidates all biological safety evidence.
It must demonstrate that residual biological risks have been reduced to an acceptable level and provide a clear scientific interpretation of the results obtained and the decisions made. It must include an analysis of any gaps and explain how these gaps do not result in uncontrolled risks. It must also document the use of historical data or biological equivalence.
➡️ Develop a BEP and a BER: Strengthen the scientific rationale, harmonize internal data, establish a robust documentation process, and review existing files.
🧠 Conclusion
ISO 10993-1:2025, published on November 18, 2025, marks a major and transformative shift in the biological evaluation of medical devices. It moves away from an approach centered on a “list of tests to be performed” to adopt a methodology that is deeply integrated with risk management, aligned with ISO 14971, and extended to the entire life cycle of the device.
This edition introduces essential clarifications, strengthens documentation requirements (particularly through the BEP and BER), and places greater emphasis on physicochemical characterization, analysis of existing data, scientific justification, and the systematic use of alternative methods (the 3Rs principle).