After seven years since the last major revision, ISO 10993-1:2025 was published on November 18, 2025, ushering in a fundamental shift in how medical device manufacturers approach biological safety evaluation. This sixth edition isn't just an update—it's a paradigm change that transforms biocompatibility testing from a checkbox exercise into a truly risk-based, scientifically justified process.
What Is ISO 10993-1?
ISO 10993-1 is the cornerstone standard for biological evaluation of medical devices, defining the principles and requirements for assessing a device's biological safety within the broader risk management framework established by ISO 14971. It guides manufacturers through identifying, assessing, and managing biological risks associated with materials, design choices, and tissue contact during a device's intended use.
The Major Shift: From Checkbox to Critical Thinking
Goodbye, Table A1
The most significant change? The prescriptive Table A1 from ISO 10993-1:2018 has been replaced by a risk-based framework. For years, manufacturers relied on Table A1 as a shopping list—if your device touched intact skin for less than 24 hours, you knew exactly which boxes to check. This approach provided comfort and predictability but came at a cost.
The problem? Companies sometimes conducted unnecessary tests simply because they appeared on the checklist, while genuine risks that fell outside standard categories sometimes went unaddressed. The checkbox mentality created an illusion of comprehensive safety evaluation while potentially missing device-specific hazards.
The New Question
Instead of asking "Which tests must we perform?" the 2025 standard pushes companies to ask "What biological safety risks does our device actually present?" This fundamental reframing requires deeper understanding of your device, its materials, and its interactions with the human body.
Key Changes in ISO 10993-1:2025
1. Complete Alignment with ISO 14971
ISO 10993-1:2025 now functions as a biologically focused extension of ISO 14971, with biological evaluation presented as a portion of the overall risk management process. The standard now uses ISO 14971's terminology, principles, and flow throughout, including:
- Biological hazard identification
- Biological hazardous situations
- Biological harm assessment
- Risk estimation and evaluation
- Risk control strategies
2. Updated Terminology
The standard introduces more precise language aligned with risk management:
- "Biological endpoints" → "Biological effects"
- New terms: biological harm, biological hazard, biological risk analysis
- "Effects after implantation" changed to "local effects after tissue contact", recognizing that non-implanted devices can also cause local biological responses
3. Four New Tables Replace Table A1
The single Table A1 has been split into four tables that better address diverse device types and contact scenarios, encouraging comprehensive safety assessments rather than minimum compliance.
4. Reasonably Foreseeable Misuse
The scope now includes not only the intended use of the device, but also reasonably foreseeable misuse, requiring additional considerations for evaluators. Manufacturers must now think beyond perfect-world scenarios and consider realistic patterns of human error or creative usage.
5. Lifecycle-Based Evaluation
The standard introduces a structured biological evaluation process that mimics ISO 14971's lifecycle approach, ensuring that biological safety is assessed from design through post-market surveillance. This isn't a one-time assessment—it's an ongoing commitment.
6. Enhanced Documentation Requirements
The biological evaluation report must document conformity with the evaluation plan and provide a rationale for decisions, aligning with ISO 14971's requirements for risk management documentation. Every decision must be justified with scientific reasoning.
What This Means for Manufacturers
Do You Need More Testing?
Not necessarily. If you truly understand your device's risks, testing requirements may remain similar or even decrease. Additional testing only becomes necessary when the risk-based approach reveals previously unconsidered biological hazards.
Must You Redo Everything?
The standard does not mandate re-testing of devices with acceptable safety histories. However, historical information must be systematically reviewed and documented to ensure that any differences do not impact the safety conclusion.
The real question is: Have you been checking boxes or truly assessing risks? If you've been following a genuine risk-based approach, updates may be minimal. If you've been relying on Table A1 as a prescription, you have work to do.
Action Steps
- Review the full standard - Download and thoroughly understand ISO 10993-1:2025
- Conduct a gap analysis - Compare your current biological evaluation framework against the new requirements
- Update documentation - Revise Biological Evaluation Plans (BEPs) and Biological Evaluation Reports (BERs) to emphasize risk justification
- Train your team - Ensure personnel understand risk estimation, hazard identification, and the new terminology
- Engage early with notified bodies - Discuss transition strategies, especially for EU MDR compliance
Regulatory Timeline
- European Union: No official grace period has been confirmed. The latest edition is being considered state of the art according to the Medical Device Regulation (MDR), so manufacturers should discuss transition plans with their Notified Bodies.
- United States: Recognition is dependent on the FDA. Monitor FDA communications for guidance on adoption timelines.
The Bottom Line
ISO 10993-1:2025 represents more than a technical update—it's a philosophical shift toward genuine risk-based thinking. The days of treating biocompatibility as a checklist exercise are over. Manufacturers who embrace this change early, develop robust risk assessment capabilities, and build scientifically justified biological evaluation programs will not only achieve compliance but also build safer medical devices and stronger regulatory submissions.
The standard challenges us to be better stewards of patient safety by asking the right questions, applying scientific rigor, and thinking critically about biological risks throughout a device's entire lifecycle. It's time to abandon checkbox thinking and embrace the complexity of true biological safety evaluation.