ISO 10993-1 has long served as the foundational standard for the biological evaluation of medical devices. The 2025 revision represents a significant evolution in how biological safety is assessed, documented and integrated into overall device risk management. Rather than focusing on a checklist of biological tests, the updated standard formalises a lifecycle based, risk driven framework aligned with ISO 14971 and strengthened regulatory expectations under EU MDR and FDA scrutiny. For manufacturers and regulatory teams, understanding the practical implications of ISO 10993-1:2025 is essential for updating Biological Evaluation Plans and Biological Evaluation Reports and ensuring ongoing compliance.
Background and Scope of ISO 10993-1
ISO 10993 is a series of standards addressing the biological evaluation of medical devices. Part 1 defines the overall framework and applies to all medical devices with direct or indirect body contact. It establishes how biological risks should be identified, assessed and controlled within the broader risk management system. The standard does not prescribe automatic testing requirements. Instead, it defines a structured approach to determine what data are necessary based on intended use, device characteristics and patient exposure.
Why ISO 10993-1 Was Revised
The revision reflects several important drivers. Alignment with ISO 14971 risk management principles was required to ensure consistency between biological risk evaluation and overall device risk management. Regulatory scrutiny has intensified under EU MDR and through evolving FDA expectations, particularly regarding justification of testing strategies and chemical safety assessments. Earlier versions of the standard were sometimes applied in a test-driven manner, with excessive reliance on animal studies rather than scientific rationale. The new edition addresses these issues by reinforcing risk-based thinking and lifecycle evaluation.
From Test Driven Compliance to Risk-Based Evaluation
One of the most significant conceptual shifts in ISO 10993-1:2025 is the move away from test-driven compliance. Under older approaches, manufacturers often selected biological tests based primarily on contact category tables without fully integrating device-specific risk considerations. The revised standard emphasises that biological evaluation is not synonymous with biological testing. Testing may be required, but only after systematic identification and evaluation of biological risks.
Biological evaluation must now be demonstrably integrated into the overall risk management file. Biological hazards are identified, risks are evaluated, control measures are defined and verification activities are conducted in alignment with ISO 14971. The process must be documented within a structured Biological Evaluation Plan and supported by a weight of evidence assessment.
Lifecycle Based Biological Evaluation
ISO 10993-1:2025 explicitly introduces a lifecycle perspective. Biological evaluation is no longer confined to the design verification stage. Instead, it must consider all phases of the device lifecycle.
This includes design and material selection, where early decisions regarding polymers, coatings, additives and manufacturing residues influence biocompatibility risk. Manufacturing processes must be evaluated for potential introduction of contaminants, processing aids or chemical residues. Clinical use and reprocessing conditions must be assessed, particularly for reusable devices where cleaning, sterilisation or repeated patient contact may alter exposure profiles. Post-market surveillance data must also inform ongoing biological risk assessment. Complaints, adverse events and field experience may trigger reassessment of biological safety assumptions.
Greater Emphasis on Intended Use
The revised standard reinforces the importance of clearly defining intended use and contact characteristics as the foundation of biological evaluation. Evaluation must explicitly consider the user population, including vulnerable groups where relevant. Anatomical contact type, such as skin, mucosal membrane, blood or implanted tissue, must be clearly characterised. Duration and frequency of contact must be defined accurately, with refined definitions for contact days and exposure categories. Clinical context must also be taken into account, including whether the device is used in acute, chronic or repeated settings.
This clarification reduces ambiguity and strengthens the link between exposure profile and biological risk assessment. It also aligns biological evaluation more closely with the intended purpose and clinical evaluation documentation required under EU MDR.
Terminology Clarification and Weight of Evidence
ISO 10993-1:2025 improves clarity around terminology and intent. A key distinction is made between biological evaluation and biological testing. Biological evaluation encompasses the full risk assessment process, including literature review, existing data analysis, chemical characterisation and testing where justified.
The role of chemical characterisation is strengthened, and weight of evidence assessments are emphasised. Manufacturers must evaluate all available data, including historical use of materials, published literature, in vitro studies and chemical analysis results, before determining whether additional testing is required. The shift in terminology from biological endpoints to biological effects reflects a more holistic and scientifically grounded approach.
Chemical Characterisation as the Default Starting Point
A major practical change is the formal positioning of chemical characterisation under ISO 10993-18 as the default starting point for most biological evaluations. Rather than beginning with animal testing, manufacturers are expected to conduct extractables and leachables analysis, identify chemical constituents and assess toxicological risk through established safety thresholds.
Chemical data inform toxicological risk assessments and may eliminate the need for certain biological tests. This approach supports more precise risk control and reduces unnecessary animal use. It also aligns with regulatory expectations under EU MDR, where notified bodies increasingly scrutinise toxicological justifications and chemical safety documentation.
Reduction in Animal Testing
The 2025 revision reinforces the principle of avoiding unnecessary animal studies. Greater emphasis is placed on existing data, in vitro testing methods, scientifically justified waivers and alternative approaches. Animal testing should only be conducted when no adequate alternative exists and when justified by risk assessment.
This change reflects both ethical considerations and advances in analytical and in vitro methodologies. Manufacturers must document clear justification for any animal testing included in the Biological Evaluation Plan.
Integration of Biological Risk into Overall Risk Management
Biological risks must now be clearly identified, evaluated, controlled and verified within the overall risk management process. Foreseeable misuse must also be considered as part of exposure assessment. Biological hazards are no longer treated as separate from mechanical, electrical or software risks. Instead, they form part of the integrated risk profile of the device.
This integration requires cross-functional collaboration between regulatory, clinical, materials science and manufacturing teams. Biological evaluation cannot be performed in isolation but must reflect the full design and lifecycle context of the device.
Practical Implications for BEP and BER Updates
Manufacturers will need to review and update their Biological Evaluation Plans to reflect the lifecycle and risk-based emphasis of ISO 10993-1:2025. BEPs should clearly define intended use, material characteristics, exposure categories and chemical characterisation strategy. They should outline how weight of evidence will be applied and how decisions regarding testing are justified.
Biological Evaluation Reports must demonstrate traceability to risk management, incorporate chemical characterisation findings and document post-market considerations where relevant. Greater transparency and scientific rationale will be expected by notified bodies and regulators.
Regulatory Expectations Under EU MDR
Under EU MDR, notified bodies expect robust integration between biological evaluation, risk management and clinical evaluation. The revised ISO 10993-1 provides a framework that aligns more closely with MDR Annex I general safety and performance requirements. Manufacturers must ensure that biological evaluation documentation clearly demonstrates conformity and addresses chemical safety, toxicological risk and lifecycle considerations.
Strategic Considerations for Manufacturers
ISO 10993-1:2025 encourages early engagement with materials experts and toxicologists during device development. Proactive chemical characterisation planning can reduce downstream testing requirements and regulatory delays. Lifecycle thinking should be embedded from design through post-market surveillance. Clear documentation and structured justification are essential. Manufacturers that adopt a scientifically grounded, risk-based approach will be better positioned for regulatory review under increasingly stringent scrutiny.
LFH supports manufacturers in interpreting ISO 10993-1:2025, updating Biological Evaluation Plans and Reports and aligning chemical characterisation strategies with EU MDR expectations. Our regulatory and clinical specialists provide structured, scientifically robust support to ensure compliance while reducing unnecessary testing and accelerating certification pathways.
FAQs – ISO 10993-1
Does ISO 10993-1:2025 eliminate biological testing entirely?
No, testing may still be required, but only after a structured risk-based evaluation.
Is chemical characterisation now mandatory for all devices?
Chemical characterisation is considered the default starting point for most evaluations.
Does the new standard apply to all medical devices with body contact?
Yes, it applies to all devices with direct or indirect body contact.
Are animal studies still permitted?
Yes, but only when scientifically justified and when alternatives are insufficient.
Must foreseeable misuse be considered in biological evaluation?
Yes, foreseeable misuse must be included in exposure and risk assessment.
Will notified bodies expect updated BEPs and BERs?
Yes, documentation must reflect the lifecycle and risk-based approach of ISO 10993-1:2025.
