Written by Diego Rodriguez, Regulatory Consultant & Alberto Bardají de Quixano, Head of Medical Devices.
A physician does not request every possible test for every patient simply because the tests exist. First, the physician understands the patient, the symptoms, the history, and the risk factors. Then the physician decides which tests are necessary to confirm or rule out a concern.
The same logic now applies to medical device biocompatibility.
When ISO 10993-1:2025 was published in November 2025, it marked one of the most significant evolutions in biological evaluation of medical devices in decades. At first glance, the update may appear to be a refinement. In reality, it represents a fundamental shift in philosophy; biocompatibility is no longer a testing exercise. It is a risk management process.
For manufacturers, this means rethinking how biological evaluation is approached, both for existing devices and new developments. Many manufacturers continue to ask the wrong question; “Which tests do we need to perform now?” The better question is; “What biological risks are relevant for this device, and what evidence do we need to justify its safety?”
This article breaks down the eight major shifts in ISO 10993-1:2025, what they mean for your organization, and how to implement them without unnecessary cost or delay.
What Changed: The Eight Major Shifts in ISO 10993-1:2025
The 2025 revision of ISO 10993-1 does not introduce completely new concepts, but it significantly clarifies, strengthens, and restructures existing principles. According to Diego Rodriguez Muñoz, RA Specialist at MDx CRO, the shift from checklist compliance to risk-based assessment represents a maturation in how the industry understands biocompatibility:
“The philosophy changed because ISO 10993-1:2025 reinforces that biological safety cannot be demonstrated only by completing a predefined list of tests. A medical device is biologically safe when the manufacturer can demonstrate, through a structured risk-based evaluation, that the materials, contact type, exposure, manufacturing process, lifecycle, and available evidence have been properly assessed.”
1. From Matrix-Based Testing to Risk-Based Biological Assessment
For decades, biological evaluation was driven by predefined test matrices. The approach was straightforward; identify your device category, look up the matrix, perform the tests listed. It felt objective. It felt safe.
ISO 10993-1:2025 closes this approach permanently.
The new standard makes explicit what should have been obvious; the purpose of biological evaluation is not to complete a checklist. The purpose is to demonstrate that a device is biologically safe through structured, scientific assessment of actual biological risks.
- The old mindset: “Which tests do we need?”
- The new mindset: “What are the biological risks, and what evidence justifies safety?”
This shift appears subtle, but it is not. It fundamentally changes how you plan a biological evaluation.
Consider a scenario; a silicone implant intended for long-term use. Under the old approach, you would follow the matrix, run all prescribed tests, check the boxes, and declare compliance. Under the new approach, you start by understanding the device; its materials, how it contacts tissue, how long it stays in the body, what could go wrong, and what evidence already exists to address each risk. If existing data satisfies the risk assessment, additional testing may not be needed. If gaps exist, testing is targeted to those gaps.
The outcome is more scientific justification; potentially fewer unnecessary tests; better decisions about where to invest resources.
Many manufacturers worry that ISO 10993-1:2025 means “more testing.” Often, the opposite is true. As Diego explains, the key message is not that the new standard
requires additional tests;
“The new standard is not about automatically adding more tests, but about building a stronger scientific justification based on the device materials, contact type, exposure, manufacturing process, lifecycle, and overall biological risk profile.”
If your planning is thorough and your rationale is sound, testing requirements may actually decrease.
2. Chemical Characterization Becomes the Foundation for Biological Evaluation
Before ISO 10993-1:2025, chemical characterization existed. It was important. But it often played a secondary role to biological testing, now it is central.
ISO 10993-1:2025 prioritizes a clear evaluation logic:
- First: understand the materials and constituents (detailed chemical characterization)
- Then: perform toxicological risk assessment based on that information
- Finally: conduct biological testing only if relevant gaps remain
This reordering is profound because chemical characterization is preventive. If you understand what a material releases, you can estimate whether those substances pose toxicological risk without animal testing. If the risk is low and well-justified, biological testing becomes optional rather than mandatory.
Why manufacturers historically missed this: Many organizations focused on “what tests can we run?” rather than “what do we know about our materials?” Chemical data; extractables, leachables, composition; was treated as supporting information. ISO 10993-1:2025 elevates it to decision-making status.
The practical impact: If chemical characterization is properly planned from the beginning, it can avoid unnecessary testing and may reduce the need for animal testing by providing stronger scientific justification for biological safety. This matters both for timelines and costs. Missing chemical information early can delay the evaluation or require remedial work later; when it is expensive to fix.
3. Device Categorization Based on Actual Contact Type Instead of Device Classification
ISO 10993-1:2025 reorganized how devices are categorized. The shift moves away from treating device category as a fixed label toward defining it based on actual biological interaction.
Devices are now assessed according to the type of body contact;
- Intact skin contact
- Mucosal surface contact
- Compromised tissue or internal tissues (non-blood)
- Blood contact
For many devices, this change has not created a major practical “category move.” But it has shifted how manufacturers think about categorization; less about what the device is (for example, “implant”), more about where and how it touches the body.
Real example, dental products for long-term oral use: Zirconia dental products intended for long-term oral use were already assessed based on their contact with the oral environment; mucosal/oral tissue exposure. Under ISO 10993-1:2025, this categorization remained appropriate, but the standard now describes the logic more clearly. The work was less about changing categories and more about confirming that contact type, exposure duration, and biological endpoints were still correctly justified.
The practical impact on the Biological Evaluation Plan (BEP) was limited in this case, but the documentation requirements became stricter. Manufacturers now need to explicitly justify why the selected contact category is correct and why the biological endpoints included in the evaluation are appropriate.
4. Biological Evaluation Plan (BEP) is Now Mandatory, Not Optional
The BEP has always existed in ISO 10993 standards, but ISO 10993-1:2025 elevates it to mandatory status with clearer expectations.
The BEP defines your evaluation strategy; which risks are relevant, how you will assess each, what data you will use, and what conclusions you will draw. It is your roadmap before you spend money on testing or documentation.
Many manufacturers skip or minimize the BEP, treating it as bureaucratic overhead. This is a mistake. A well-developed BEP prevents costly rework. It clarifies expectations with regulators before submission. It demonstrates thinking, not just activity.
ISO 10993-1:2025 expects the BEP to cover;
- Device and material description
- Contact assessment (type, duration, exposure)
- Biological hazard identification
- Information gathering strategy (what data already exists, what is needed)
- Chemical characterization plan
- Biological testing strategy (and justification for why this strategy is appropriate)
- Risk assessment approach
The BEP should be part of your design and development plan, demonstrating integration with design controls. It is a living document that evolves with your device, not a static compliance box.
5. Exposure Duration Calculated as Contact Days; Not as Continuous Hours
ISO 10993-1:2025 introduces a more clinically relevant way of assessing exposure using “contact day” logic.
Previously, manufacturers sometimes added together seconds or minutes of multiple exposures to calculate total contact duration. The new standard clarifies that any exposure counts as a minimum of one day. Two exposures means at least two days of contact, even if they total only minutes.
This matters because contact duration category affects which biological endpoints you need to address. It is not that ISO 10993-1:2025 changed the biological science; it is that it clarified how real-world use should be assessed.
Example: A bandage used for 24 hours, removed, and then reapplied for another 24 hours.
- Old approach: Could be calculated as 48 hours continuous contact
- New approach: Two separate days of contact (potentially affecting duration category)
For reusable devices or those with intermittent use, this shift can significantly influence the overall risk profile and the biological evaluation strategy.
6. Reasonably Foreseeable Misuse Must Be Evaluated in the Biological Assessment
ISO 10993-1:2025 explicitly requires consideration of reasonably foreseeable misuse; use of the device in a way not intended by the manufacturer, but in ways that can reasonably be expected based on known behavior, post-market data, or clinical literature.
This is not entirely new; it was already part of overall risk management philosophy. But ISO 10993-1:2025 makes it explicit within biological evaluation.
Example; A wound dressing intended for 24 hours of use: It is reasonably foreseeable that a patient might leave it on longer. The manufacturer should assess whether that extended exposure changes the biological risk. Does the adhesive degrade? Does moisture accumulation increase risk? Does the duration move the device into a different contact category?
This does not automatically mean additional testing is needed. But it must be justified in the BEP and BER (Biological Evaluation Report). The manufacturer must demonstrate that either (a) the extended use does not materially change risk, or (b) the biological evaluation already accounts for the extended use scenario.
7. ISO 14971 Risk Management Framework Integration, Biological Evaluation is No Longer Separate
Biological evaluation is no longer separate from overall device risk management.
ISO 10993-1:2025 aligns biological evaluation directly with ISO 14971 (risk management), adopting its structure, terminology, and logic. This means biological hazards and risks must be identified, assessed, and controlled within your comprehensive risk management framework; not in isolation.
8. Device Lifecycle Thinking, Biological Assessment Continues Beyond Launch
Biological safety is no longer assessed at a single point in time. It must be considered across the entire lifecycle of the device, including material selection, manufacturing, transport, storage, clinical use (including reuse or reprocessing), and end-of-life considerations.
Changes at any of these stages can influence biological safety and should be evaluated within the overall risk management framework.
The Real Impact: Gap Assessment Case Study for ISO 10993-1:2025 Compliance
Theory is one thing, implementation is another, here is what gap assessment looks like in practice.
A Real Case Study to illustrate ISO 10993-1:2025 Compliance
Zirconia Dental Products for Long-Term Oral Contact
The team at MDx CRO recently worked with a manufacturer of zirconia dental products intended for long-term oral contact who faced the question
every manufacturer now faces; “Does our existing biological evaluation meet ISO 10993-1:2025 expectations?” This real-world case exemplifies the practical challenges manufacturers encounter.
The challenge was not philosophical; it was practical; ensuring that the new requirements and expectations introduced by the 2025 revision were correctly interpreted and fully addressed, while making sure no relevant gap was omitted and that existing evidence was sufficient to justify that no additional testing was required.
The approach: Structured gap assessment
Rather than assume, the organization performed a systematic review against ISO 10993-1:2025;
- Intended Use; Confirmed the stated purpose, contact type, and exposure duration under the new “contact day” logic.
- Material Composition and Manufacturing; Reviewed material specifications, manufacturing process documentation, and any relevant chemical characterization data.
- Existing Biological Data; Cataloged all available biological testing results, literature references, and historical evidence.
- Contact Assessment; Confirmed whether the device contacts intact skin, mucosal surfaces, internal tissues, or blood, and verified duration categorization.
- Endpoint Assessment; For each biological endpoint relevant to the contact category, assessed whether it was;
- Already covered by existing data
- Covered but requiring stronger rationale
- Missing and requiring additional information
- Risk Management Integration; Confirmed that biological evaluation was integrated with overall device risk management (ISO 14971).
The outcome
No additional testing was required. But the biological evaluation file was updated to strengthen rationale where needed, to address the new expectations around chemical characterization, and to clearly document how each biological endpoint was justified.
The real value is clarity. The manufacturer moved from “we think we are compliant” to “here is exactly why we are compliant, and here are the gaps we identified (and why they do not require action).”
Why this matters?
This case exemplifies what regulators expect under ISO 10993-1:2025. They want to see thinking, structure, and scientific reasoning; not just test reports. A manufacturer who invests in proper gap assessment demonstrates both competence and transparency.
The Most Common Mistakes About ISO 10993-1:2025 Implementation (and How to Avoid Them)
Implementation is new, but patterns are already emerging. Here are the mistakes manufacturers are making; and how to avoid them.
Mistake #1. Continuing to Think “Testing Checklist” Instead of “Risk Assessment”
The mistake; Starting with the question “Which tests do we need?” and working backward from there.
Why it happens; The old matrix-based approach made this feel objective and safe. Changing thinking takes time.
The fix; Start with the device, its materials, its intended use, and its actual biological risks. Let the risk assessment drive decisions about what evidence is needed. Testing becomes one tool among many, not the default answer.
Mistake #2. Ignoring Chemical Characterization Data in the Planning Phase
The mistake; Relegating chemical data to a supporting role instead of elevating it to decision-making status.
Why it happens; Historically, biological testing seemed more “rigorous” than chemistry. Many organizations lack in-house chemical expertise.
The fix; Invest in chemical characterization data upfront. Extractables/leachables analysis, material composition review, and toxicological assessment should inform your biological evaluation strategy from day one.
Mistake #3. Treating Gap Assessment as an Optional Compliance Step
The mistake; Assuming that a 2018 biological evaluation automatically “passes” under 2025 expectations without systematic review.
Why it happens; Gap assessment requires time and expertise. It is tempting to skip it and hope for the best.
The fix; Conduct a structured comparison of your existing documentation against ISO 10993-1:2025 expectations. Identify what is already covered, what needs stronger rationale, and what is genuinely missing. This investment prevents costly surprises later.
Mistake #4. Not Integrating Biological Evaluation into Overall Risk Management
The mistake; Treating biological evaluation as a standalone compliance exercise rather than as part of ISO 14971 risk management.
Why it happens; Different teams, different timelines, different reporting structures.
The fix; Ensure that biological hazards and risks are identified, assessed, and controlled within your overall risk management framework. Biological evaluation is not separate; it is integrated.
Implementing ISO 10993-1:2025, A Practical Roadmap for Device Manufacturers
Implementation varies depending on whether you are managing existing devices or developing new ones.
For Existing Devices: The Gap Assessment Path
Step 1: Gap Assessment (Weeks 1-4)
Conduct a structured review of existing biological evaluation documentation against ISO 10993-1:2025 expectations. Identify gaps, prioritize, and classify each as;
- Already adequately covered
- Covered but requiring stronger rationale
- Missing (requiring new information or testing)
Step 2; Update BEP/BER (Weeks 4-8)
Revise biological evaluation documentation to reflect new standard expectations. Strengthen rationale where needed. Document decisions clearly.
Step 3; Regulatory Alignment (Weeks 8+)
If necessary, discuss findings with notified bodies or regulatory contacts. Most manufacturers find that proper gap assessment and documentation update are sufficient; additional testing is often not required.
Timeline; 8-12 weeks for most devices, depending on complexity and existing documentation quality.
Resource needs; In-house expertise or external partner with ISO 10993-1:2025 knowledge and gap assessment experience.
For New Devices; Plan from Design Phase Forward
Step 1: BEP Development (Design Phase)
Develop the biological evaluation plan as part of your design and development plan. Define contact category, exposure duration, relevant biological endpoints, and evaluation strategy before design lock.
Step 2: Material Selection with Chemical Information in Mind
Select materials based not just on performance but on understanding chemical composition, extractables, and potential toxicological risk. This informs your testing strategy.
Step 3: Chemical Characterization Planning (Development Phase)
Conduct extractables/leachables studies and toxicological assessment in parallel with design development, not after.
Step 4: Risk-Based Testing Strategy
Determine which biological tests (if any) are necessary based on chemical data and risk assessment. Avoid reflexive testing; justify each test against identified risks.
Step 5: BER Documentation
Upon completion, compile biological evaluation report demonstrating how each identified risk was addressed and why the device is biologically safe.
Timeline: Integrated into normal device development; no additional timeline required if planned properly.
Resource needs: Access to biological evaluation expertise early in development.
Key Deliverables: BEP and BER
Biological Evaluation Plan (BEP):
- Device description and intended use
- Contact assessment (type, duration)
- Material composition and chemical characterization strategy
- Biological hazard identification
- Information gathering and testing strategy
- Expected outcomes and decision criteria
Biological Evaluation Report (BER):
- Executive summary of findings and conclusions
- Device and material description
- Contact assessment
- Chemical characterization results
- Toxicological risk assessment
- Biological test results (where conducted)
- Literature review
- Overall risk evaluation
- Safety conclusion with scientific justification
Both documents must demonstrate traceability; every claim must be supported by evidence or clear scientific reasoning.
Regulatory Alignment EU and FDA Approaches to ISO 10993-1:2025
EU perspective; The Medical Device Regulation (MDR) recognizes ISO 10993-1:2025 as state-of-the-art. Notified bodies are already aligning with the 2025 revision. Manufacturers seeking CE marking should plan for ISO 10993-1:2025 compliance.
FDA perspective; The FDA has not yet formally recognized ISO 10993-1:2025 in its official database of recognized consensus standards. However, FDA’s draft guidance on “Chemical Analysis for Biocompatibility Assessment” (published September 2024) aligns with the risk-based, chemistry-forward approach of the 2025 standard. FDA recognition is expected, but timelines are typically 12-24 months behind EU adoption.
For manufacturers in both markets; Plan for ISO 10993-1:2025 compliance. The scientific approach aligns across both regions. No major friction is expected between EU and FDA interpretations; the main difference will be adoption timeline.
Why ISO 10993-1:2025 Matters Beyond Compliance and Testing Requirements
The shift to risk-based biological evaluation is not just regulatory; it is patient-centric.
Patient Safety; A more rigorous risk assessment process, grounded in materials science and clinical understanding, identifies and controls biological risks more effectively than checklist compliance.
Animal Welfare; Smart chemical characterization means fewer animals used in testing. By using data-driven approaches to inform testing decisions, manufacturers can justify reduced animal use without compromising safety.
Business Case; Proper planning reduces rework, prevents unnecessary testing, and accelerates time to market. Manufacturers who invest in structured biological evaluation planning see faster regulatory approval and lower development costs.
Regulatory Confidence; Risk-based, scientifically justified evidence carries more weight than checkbox compliance. When you present a regulator with clear thinking and evidence, approval is more straightforward.
When to Bring in Expert Support for ISO 10993-1:2025 Compliance
ISO 10993-1:2025 implementation is manageable with the right expertise. Here are the signs you might benefit from external guidance.
Red flags that expert support would help;
- You are unsure about your device’s contact category under the new standard
- Your chemical characterization data is incomplete or unclear
- Performing gap assessment feels overwhelming given your internal resources
- Your timeline is tight and you cannot afford delays
- You have received preliminary feedback from regulators and need guidance on responding
What expert guidance typically includes;
- Gap assessment and recommendations
- BEP/BER review and strengthening
- Risk strategy development
- Regulatory interaction support
- Timeline and resource planning
The right partner brings three things; deep ISO 10993-1:2025 knowledge, regulatory experience, and practical understanding of device development. They help you avoid the expensive mistakes while accelerating toward approval.
Gap Assessment Checklist
To support your ISO 10993-1:2025 compliance review, we have created a detailed gap assessment checklist that walks you through each requirement step-by-step.
This checklist includes;
- 15-20 assessment questions
- Scoring rubric (Low Risk / Medium Risk / High Risk)
- Next steps based on your assessment results
- Regulatory alignment guidance
Access the Gap Assessment Checklist
ISO 10993-1:2025 is not a burden; it is clarity.
For decades, the testing matrix provided a false sense of objectivity. Manufacturers could follow the rules and feel confident. ISO 10993-1:2025 removes that illusion and demands something better; thinking.
The shift from “checklist mentality” to “risk-based assessment” reflects a mature understanding of what biocompatibility truly means. It is not about running a certain number of tests. It is about demonstrating, through structured evaluation and scientific reasoning, that a device is safe for its intended use.
Manufacturers who embrace this shift early will see benefits;
- More efficient biological evaluation
- Faster regulatory approval
- Better patient safety outcomes
- Reduced unnecessary animal testing
The standard is new, but the direction is clear. Whether you are managing existing devices or developing new ones, the time to act is now. Early implementation positions you ahead of competitors and demonstrates commitment to robust biological safety.
If your organization is ready to align with ISO 10993-1:2025, a structured gap assessment and risk-based biological evaluation strategy is the starting point. That is where clarity begins.
