ISO 10993-1:2025: Enhanced Characterization, Clearer Risk Logic
The 2025 revision keeps biological evaluation firmly inside ISO 14971 risk management and across the full device life cycle. Your plan-and-report pair matters more than ever: the biological evaluation plan (BEP) must spell out intended use, reasonably foreseeable misuse, categorization, characteristics related to biological safety, hazards and acceptability criteria, gap analysis, strategy, competencies, and responsible personnel; the biological evaluation report (BER) must show conformance to the plan and explain how each biological effect was addressed, including the rationale for test selection or waivers and the overall conclusions on residual biological risk. Evaluations must be revisited when post-market information or product/process changes could affect safety.
The standard now leans first on information. Chemical characterization (ISO 10993-18) is the central input that focus the evaluation and guide test selection; where adequate, relevant information exists, animal studies should be minimized or not performed. Testing, if needed, is selected by type/duration of body contact and justified in the BEP, using the ISO 10993 series as the primary map. Annex A explains how to use chemical data and why and when this analysis is necessary.
ISO 10993-1:2025 also calls out physical characteristics as potential risks. Particle generation and material defects (e.g. porosity, sharp edges) can create biological hazards. The standard now treats particulate risk “through a risk lens”. Even devices contacting skin or mucosa warrant justification of particulate safety. Two scenarios must be considered: manufacturing residual particles (e.g. glass or metal debris from cutting) and wear-generated particles (e.g. flaking from friction). For each, the BEP should assess if particles could dislodge and where they might accumulate. Notably, particles that bioaccumulate in tissue effectively lengthen exposure – ISO 10993-1 now requires treating those cases as long-term exposure. For example, a porous ceramic implant might release fine particles over time. If those particles can lodge in bone or be transported systemically, the risk assessment must address “local effects after tissue contact” even for a non-implant device.
Foreseeable misuse:Consider misuse as part of both planning and categorization, and base it on real-world evidence. Use post-market data and clinical literature to identify situations where the device is used outside the intended use in a way that is systematic. If such misuse is likely, adjust the device categorization and exposure assumptions and include it in the BEP. Document in the BER what you considered and how you addressed it. For example, a bladder catheter left in for weeks instead of days should be treated as a longer exposure and can change the endpoints you assess. Another example is a guidewire routed through a different vascular path, which changes the body contact site and can alter the biological effects to consider.
If risk from a misuse scenario is above your acceptability criteria, refine the estimate first. Improve constituent quantification, gather stronger literature, or run targeted testing. Then apply risk controls in the priority order set by ISO 14971. Start with inherently safer design and manufacture, then use protective measures in the device or process, then provide information for safety and training. Re-evaluate and document residual risk.
Life-cycle perspective (Clause 4.3): Treat device change over time and the full life cycle together. The biological evaluation must cover transport, storage, handling, use, reprocessing, and end of life, and it must be maintained across the life of the device. Anticipate material changes during transport or storage that could alter safety. For reusable devices, set and validate the claimed number of processing cycles. If the maximum number is not specified, justify the biological risk controls. Post-market information can trigger updates to the evaluation. For single-use devices, identify and test the worst case condition. Depending on materials and packaging, the worst case can be at release or at end of shelf life. Choose representative or worst case samples and account for life-cycle changes in sample selection.
Changes caused by composition or use are addressed explicitly. If the device is absorbable or if chemical or physical degradation including wear can occur, document mechanisms, rates, and the parameters that drive them. Simulate expected degradation in vitro. Perform in vivo degradation or kinetic studies only when in vitro or clinical evidence is insufficient. Evaluate the impact of particulates from residuals, wear, or degradation on both local and systemic effects, considering physical attributes and potential release of substances. Consider toxicokinetics, including absorption, distribution, metabolism, and excretion, when devices are absorbable, are long term implants with degradation or corrosion, are likely to release substantial quantities of constituents or nano-objects, or are drug device combinations. Toxicokinetic studies follow ISO 10993-16 and should start with in vitro work where possible.
In essence, Clause 4.3 calls for demonstrating biological safety under real-world conditions across the product life cycle and for updating conclusions when new information or process changes arise.
Finally, the updated standard reinforces that all identified biological hazards must be traced through the life cycle. For instance, if an additive is present only before sterilization but is removed during processing, this should be documented. Conversely, if a processing aid (like a lubricant) is found on the final device, its biological impact must be evaluated. In summary, device characterization now includes a thorough analysis of what the materials and processing introduce, how they may degrade or deposit, and when in the product life cycle these events occur. Each of these factors (formulation details, potential residues, physical defects, and misuse) is expected to be considered and justified in the BEP and BER.
About the Author: Prof. Łukasz Szymański
Prof. Łukasz Szymański is an expert in medical device biocompatibility testing, serving as the Chief Scientific Officer (CSO) of the ISO 17025-accredited and GLP-certified European Biomedical Institute (EBI) and North American Biomedical Institute (NABI). As a dedicated researcher and a key contributor to advancing safety standards in the biomedical field, Prof. Szymański plays an integral role in shaping scientific innovations and regulatory compliance within the industry.