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The 2025 revision of ISO 10993‑1 introduces several important updates that reshape how manufacturers plan, justify, and document the biological evaluation of medical devices. The revised standard strenghtens the link between biological safety and risk management, redefines how exposure duration is determined, introduces new device contact categories, and clarifies requirements for using existing data and assessing sensitive populations.
Aligned terminology: The standard now adopts risk‑management terms such as biological hazard, biologically hazardous situation, biological harm, and residual biological risk, ensuring consistency across risk‑management documents
BEP/BER requirements:
Qualified personnel: Biological evaluation must be performed by individuals with demonstrable competence (toxicology, chemistry, clinical evaluation, etc.), supporting scientifically defensible decisions.
Greater emphasis on existing data and alternatives: The revised standard strengthens the use of existing data, chemical characterization, and alternative approaches to support biological safety assessments and avoids unnecessary animal testing.
ISO 10993‑1:2025 positions biological evaluation as a risk‑driven, lifecycle process rather than a standalone check. Biological safety must be actively managed, scientifically justified, and transparently documented—evolving with the device and its risks.
ISO 10993‑1:2025 introduces a use‑based, cumulative approach to defining exposure duration. This revised framework directly influences device categorization and the scope of biological evaluation.
Contact day:
Exposure is defined by contact days, meaning any day a device or its components contact the patient, regardless of contact duration within that day.
Total exposure period:
Device classification is based on the total number of contact days between first and last use.
Bioaccumulation default rule:
Materials or constituents with bioaccumulation potential must be classified as long‑term exposure, unless a scientific justification supports otherwise.
Exposure classification must include both intended use and foreseeable misuse, such as:
Under ISO 10993‑1:2018, devices with short contact durations could often be classified as limited exposure. Under the revised definition, repeated or intermittent use may shift a device into prolonged or long‑term exposure, unless scientifically justified otherwise. This reclassification can expand the required biological evaluation, particularly for systemic effects.
ISO 10993‑1:2025 replaces the traditional single contact matrix with four body contact categories, providing a clearer framework for selecting relevant biological endpoints.
Devices are classified according to where they contact the body:
Legacy terms such as “externally communicating devices” have been removed, simplifying classification and interpretation..
Each contact category table is associated with a set of core biological endpoints, which may include:
Depending on the device, additional endpoints may also need to be considered, such as immunotoxicity, neurotoxicity, reproductive and developmental toxicity, or material‑mediated pyrogenicity.
Key updates:
Devices within the same contact category may now require different biological evaluations, depending on exposure duration and use patterns. In particular, the mandatory inclusion of genotoxicity for prolonged or long‑term contact (except intact skin) represents a significant expansion compared to previous editions. As a result, use and exposure now drive both classification and endpoint selection.
ISO 10993‑1:2025 introduces a clearer and more structured framework for biological equivalence, defining when existing biological data from a comparable device or material may be used.
Biological equivalence is no longer based solely on similarities in material composition or manufacturing processes. Instead, the focus is on whether patient‑relevant biological risks are comparable under the intended conditions of use.
To support an equivalence claim, manufacturers must provide a clear and well‑structured scientific justification, documented within the Biological Evaluation Plan (BEP) and Biological Evaluation Report (BER). This justification should demonstrate that the available data are applicable to the device under evaluation and adequately address its biological safety.
Demonstrating biological equivalence supports transparent and scientifically sound use of existing data and can reduce the need for additional testing, including animal studies, while maintaining patient‑relevant biological safety.
ISO 10993‑1:2025 places stronger emphasis on evaluating biological safety for sensitive or vulnerable patient groups, ensuring that potential risks are considered beyond the “average” adult user.
Who to consider:
Manufacturers should consider patient groups that may have increased susceptibility, including children and infants, elderly patients, chronically ill patients, pregnant individuals, women of child‑bearing age, and immunocompromised patients.
What to assess:
For these populations, it must be evaluated whether materials, leachables, or degradation products could result in different or higher biological risks compared to the general population.
Documented justification:
Any specific considerations related to sensitive populations must be identified, evaluated, and scientifically justified within the Biological Evaluation Plan (BEP) and Biological Evaluation Report (BER).
Considering sensitive populations ensures that biological safety assessments reflect real‑world clinical use and patient diversity, supporting a more robust and clinically relevant evaluation.
The updated ISO 10993‑1:2025 framework places greater emphasis on structured documentation, risk‑based justification, and scientifically sound biological evaluation. We support manufacturers in meeting these expectations through targeted, expert‑driven services.
BEP & BER support
We prepare or update Biological Evaluation Plans (BEP) and Biological Evaluation Reports (BER) in line with ISO 10993‑1:2025, including:
Toxicological Risk Assessment (ISO 10993‑17:2023)
We perform dose‑response and exposure‑based toxicological risk assessments (TRA) compliant with ISO 10993‑17:2023, including the derivation of:
Study monitoring
We provide scientific oversight of biological and toxicological studies, ensuring alignment with the BEP, ISO expectations, and regulatory requirements.
ISO 10993-1:2025 defines the principles and framework for the biological evaluation of medical devices. The revised standard strengthens the integration between biological evaluation and risk management according to ISO 14971. It introduces a lifecycle-based approach, where biological safety is continuously evaluated based on device changes, clinical use, materials, exposure, and new information.
The main updates include stronger risk management integration, revised exposure duration concepts, new body contact categories, updated biological endpoint selection, clearer requirements for biological equivalence, and increased consideration of sensitive patient populations. These changes aim to make biological evaluations more risk-based, scientifically justified, and aligned with actual device use.
ISO 10993-1:2025 shifts biological evaluation from a one-time assessment to a continuous lifecycle process. Manufacturers should identify biological hazards, evaluate potential harm, implement appropriate controls, and reassess risks when changes occur, such as modifications to materials, manufacturing processes, sterilization methods, or intended use.
ISO 10993-1:2025 emphasizes the role of the BEP and BER in documenting biological safety decisions. The BEP should define biological risks, relevant endpoints, evaluation strategy, acceptability criteria, and justification for testing or existing data use. The BER should evaluate available evidence and demonstrate whether residual biological risks are acceptable.
Yes. ISO 10993-1:2025 supports the use of existing biological data, chemical characterization, and alternative approaches when scientifically justified. Manufacturers must demonstrate that available information adequately addresses biological risks, reducing unnecessary testing while maintaining patient safety.
A contact day is any day during which a medical device or its components contact the patient, regardless of how long contact occurs on that day. This approach ensures that repeated patient exposure is considered when determining the appropriate exposure category and biological evaluation requirements.
ISO 10993-1:2025 introduces a cumulative, use-based approach for determining exposure duration. Classification is based on the total number of contact days between the first and last use of the device. This means repeated or intermittent use may result in a longer exposure classification than under previous approaches, potentially affecting the required biological evaluation.
ISO 10993-1:2025 introduces four body contact categories to replace the previous contact matrix approach. These categories are:
The new structure provides a clearer basis for selecting relevant biological endpoints according to the type of patient contact.
ISO 10993-1:2025 identifies core biological endpoints that may need evaluation, including cytotoxicity, sensitisation, irritation, systemic toxicity, local effects after tissue contact, genotoxicity, carcinogenicity, and hemocompatibility. Additional endpoints, such as immunotoxicity, neurotoxicity, reproductive toxicity, developmental toxicity, or material-mediated pyrogenicity, may be considered depending on device-specific risks.
ISO 10993-1:2025 requires consideration of genotoxicity for devices with prolonged or long-term contact, except devices limited to intact skin contact. The need for genotoxicity assessment should be scientifically justified based on the device materials, exposure conditions, chemical characterization data, and potential biological risks.
ISO 10993-1:2025 allows manufacturers to use existing biological safety data from a comparable medical device when biological equivalence is demonstrated. This requires sufficient similarity in factors relevant to biological safety, including body contact, duration of contact, composition, physical characteristics, manufacturing processes, patient population, and material quantity.
The assessment should confirm that any differences do not introduce new or increased biological risks. Biological equivalence is supported by evaluating chemical, physical, material, and contact equivalence. The justification should be documented in the Biological Evaluation Report (BER).
ISO 10993-1:2025 places greater emphasis on evaluating biological risks for sensitive populations. These may include children, infants, elderly patients, pregnant individuals, women of child-bearing age, chronically ill patients, and immunocompromised patients. Manufacturers should consider whether differences in susceptibility may affect the biological safety assessment and document the justification within the BEP and BER.
Manufacturers should review their biological evaluation processes and update documentation strategies to align with the revised standard. Key actions include reassessing exposure duration, reviewing biological endpoints, strengthening risk management links, evaluating existing data, and ensuring that BEP and BER documentation provides clear scientific justification.
Agirad supports medical device manufacturers with ISO 10993-1:2025 biological evaluation activities, including preparation and review of Biological Evaluation Plans (BEP), Biological Evaluation Reports (BER), toxicological risk assessments according to ISO 10993-17:2023, and scientific oversight of biological studies. Our support helps manufacturers develop scientifically justified assessments aligned with regulatory expectations.