ISO 10993-1 has always been the framework standard for the biological evaluation of medical devices. The 2025 revision doubles down on that role: it positions biological evaluation explicitly within a lifecycle risk-management process, tightens expectations on chemical characterisation, and raises the bar on how you justify test strategies and residual risks.
For MDR manufacturers, that matters. A Biological Evaluation Report (BER) that looked acceptable under the 2018 edition may now prompt Notified Bodies to ask awkward questions:
- Is your chemistry data robust enough?
- Does your BER actually connect to the ISO 14971 risk file?
- Have you justified why you did (or didn’t) run specific biocompatibility tests?
If not, you’re looking at extra rounds of questions, additional testing, and possible certification delays.
What is ISO 10993-1 and why it matters
ISO 10993-1:2025 is the latest edition of Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process. It sets the top-level framework for the entire ISO 10993 series – from cytotoxicity and sensitisation through to systemic toxicity and degradation products.
Regulators treat it as the reference for ISO 10993 biological safety:
- EU MDR 2017/745 expects biological safety and compatibility to be demonstrated as part of Annex I General Safety and Performance Requirements, and ISO 10993-1 is the standard most commonly used to structure that evidence.
- The US FDA formally recognised the standard in its 2023 guidance Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process”, confirming that a risk-based ISO 10993-1 approach is the default expectation for US submissions as well.
Critically, ISO 10993-1:2025 is designed to sit inside the risk management process defined by ISO 14971:2019, which sets out how to identify hazards, estimate risks, implement controls, and review them over the device lifecycle.
So if ISO 14971 is the skeleton of your risk management system, ISO 10993-1:2025 provides the biological flesh on that skeleton: what endpoints you need to consider, what evidence is acceptable, and how to judge residual biological risk.
What’s new in ISO 10993-1:2025
The 2025 revision isn’t just a tidy edit. It changes the tone of the standard from “here is a test menu” to “build a scientifically coherent risk story”. Current expert commentary highlights five broad shifts.
1. Stronger emphasis on biologically-focused risk assessment
ISO 10993-1:2025 pushes you to integrate chemistry, toxicology, pre-clinical testing, and clinical data into a single biological risk assessment – not a pile of disconnected reports. Biocompatibility is framed as a conclusion, not just a set of lab outputs.
In practice, that means:
- You must explicitly explain why the combination of chemical characterisation, test results, and clinical experience is sufficient.
- Generic “device is biocompatible based on historical use” statements will not survive Notified Body scrutiny.
2. Tighter alignment with ISO 14971
The new edition makes the link to ISO 14971 more explicit. Biological hazards and endpoints must be clearly traced into the risk management file, with risk controls and residual risk evaluation visible in the same framework used for other hazards.
That means:
- The BER can’t live in a silo.
- Biological risks, control measures, and residual-risk acceptability must show up in your ISO 14971 documentation and management review.
3. Clearer expectations for complex and long-term devices
For long-term implants, absorbable materials, coated devices, and combination designs, ISO 10993-1:2025 adds more depth around:
- Degradation behaviour and its clinical significance.
- Long-term exposure, especially for paediatric patients or chronic therapies.
- Interactions between multiple materials, coatings, and leachables.
The message is simple: if your device stays in the body for a long time, the bar for biological justification is higher – and the standard now says that out loud.
4. More weight on analytical chemistry (ISO 10993-18)
The revision leans harder on chemical characterisation as the basis for biological evaluation, in line with FDA’s draft guidance on Chemical Analysis for Biocompatibility of Medical Device Evaluations, which outlines detailed expectations for extractables/leachables study design, analytical methods, and reporting.
Expect more questions if:
- Your chemistry studies are incomplete or use poorly justified extraction conditions.
- Your toxicological risk assessments don’t clearly connect chemical findings to patient exposure and clinical risk.
5. Stricter use of existing data and literature
ISO 10993-1:2025 still allows the use of existing biocompatibility data, literature, and clinical experience, but it now makes it clearer that:
- Literature reviews must be structured and relevant to your device’s materials, manufacturing, and use.
- Any decision not to test must be backed by a written, scientifically reasoned justification, and linked back to the risk file.
For many legacy devices, that alone will force a rethink of how BERs are written and how evidence is marshalled.
Biological evaluation of medical devices – core principles
Within the medical device biocompatibility standard framework, biological evaluation is not “just testing”. It’s a staged process:
- Biological Evaluation Plan (BEP)
You define the device, materials, intended use, patient contact type and duration, and the biological endpoints you need to consider. You also set out what data you’ll rely on (chemistry, existing tests, new studies, literature, clinical data). - Hazard Identification and Endpoint Selection
Based on contact type/duration and materials, you identify potential biological hazards (cytotoxicity, sensitisation, genotoxicity, systemic toxicity, etc.) and decide which endpoints must be addressed. - Evidence Generation
You combine the right tools for the job:- Chemical characterisation (ISO 10993-18).
- In vitro or in vivo tests where truly needed.
- Published data and historical testing.
- Clinical experience and PMS information.
- Biological Evaluation Report (BER)
You then pull this together into a Biological Evaluation Report, explaining what was tested, what wasn’t, what was found, and why the residual biological risk is acceptable in light of benefits and controls.
Recent biocompatibility insight briefs emphasise that weak BER narratives, particularly ones that don’t explain endpoint omissions or link to risk management, are a frequent cause of review delays.
Integrating ISO 10993-1:2025 with ISO 14971 risk management
ISO 10993-1:2025 assumes you’re running a proper ISO 14971:2019 risk-management process. The relationship looks like this:
- ISO 14971
- Identifies all device hazards (mechanical, electrical, biological, use-related, etc.).
- Defines risk-control measures and acceptance criteria.
- Drives ongoing review of risk based on PMS.
- ISO 10993-1:2025
- Focuses on biological hazards (toxicity, sensitisation, local effects, systemic effects).
- Defines endpoints, study strategies, and evidence requirements.
- Requires you to plug biological conclusions back into the ISO 14971 risk file.
- QMS & Clinical Evaluation (MDR)
- “Consumes” the biological risk conclusions within your Technical Documentation, CER and PMS plans.
If your BER lives in a separate SharePoint folder and never speaks to the risk file, ISO 10993-1:2025 is a clear nudge that this needs to change.
Biological Evaluation Report (BER) – Do you need to update it?
Not every BER needs to be torn up overnight. But ISO 10993-1:2025 gives you a clear lens to decide when an update is wise – or necessary.
You likely need to revisit your Biological Evaluation Report if:
- Device or process changes
You’ve changed materials, additives, sterilisation methods, or manufacturing processes (e.g. replacing PFAS, switching EtO sterilisation cycles, or adding new coatings). Those changes alter the chemical picture – and regulators will expect updated biological evaluation. - Your BER is based on ISO 10993-1:2018 assumptions
If the current BER doesn’t clearly integrate chemical characterisation, toxicological risk assessment and clinical data into a single risk argument, it’s at odds with the 2025 emphasis. - Endpoint omissions are poorly justified
Statements like “no additional testing required due to historical use” without proper literature review or material characterisation are unlikely to satisfy a Notified Body. - You’ve already had biocompatibility questions
If previous MDR reviews or FDA submissions triggered questions about biocompatibility rationale, test selection or linkage to risk management, ISO 10993-1:2025 is your cue to reset the structure.
Updated testing and evaluation requirements
Chemical characterisation and material analysis
ISO 10993-1:2025 gives more prominence to ISO 10993-18 – chemical characterisation – as the starting point of biological evaluation. Rather than defaulting to a battery of in vivo tests, you’re expected to:
- Characterise extractables and leachables under realistic worst-case conditions.
- Use robust analytical methods and clear identification/quantification thresholds.
- Feed those data into a structured toxicological risk assessment.
FDA’s draft guidance on chemical analysis for biocompatibility reinforces the same message: poor or inconsistent chemistry is one of the biggest root causes of biocompatibility deficiencies in submissions.
Biological endpoints and testing selection
The 2025 edition refines the familiar matrix of biological endpoints by contact type and duration. But the spirit has shifted: the matrix is now a starting hypothesis, not an automatic test list.
You’re expected to:
- Justify why each endpoint is or isn’t relevant based on materials, exposure and clinical use.
- Avoid repeat animal testing where chemistry, tox and clinical experience already close the gap.
- Document your logic in the BEP and BER.
Use of existing data and literature
Using existing data is still very much supported, but ISO 10993-1:2025 requires:
- Structured literature reviews, with inclusion/exclusion criteria and clear relevance to your device.
- Critical appraisal of older studies and supplier data against current knowledge (e.g. emerging concerns around certain additives or degradation products).
“Copy-paste” bibliographies or vague references to “similar devices” won’t cut it under the new expectations.
Biocompatibility assessment under MDR – What changes for manufacturers?
Under EU MDR, biological safety isn’t a standalone annex – it is woven through Annexe I (GSPRs), Annexe II (Technical Documentation) and Annexe XIV (clinical evaluation).
With ISO 10993-1:2025, Notified Bodies are likely to look for:
- A Biological Evaluation Plan that explicitly cites the 2025 edition, explains endpoint selection and documents test omissions with scientific justification.
- A BER that cross-references the ISO 14971 risk file and clinical evaluation – not just a stack of lab certificates.
- Evidence that PMS and complaint data feed back into biological risk assessments, and that those updates are visible in risk files and BER versions.
For many MDR manufacturers, this will mean:
- Re-framing existing BERs rather than completely starting from scratch.
- Tightening links between toxicology, clinical and RA/QA teams.
- Planning BER updates into the MDR surveillance/renewal cycle rather than waiting for a nonconformity.
Practical Steps to Implement ISO 10993-1:2025
You don’t need a revolution; you need a structured plan. A practical roadmap could look like this:
Step 1: Run a gap assessment
Compare your current BEPs/BERs and test strategies against ISO 10993-1:2025:
- Is chemical characterisation central or an afterthought?
- Are endpoint decisions documented and justified?
- Does the BER explicitly link to the ISO 14971 risk file?
This is often best done as a joint exercise between RA/QA, toxicology and clinical teams.
Step 2: Update the Biological Evaluation Plan (BEP)
Your BEP should now:
- Describe the device, materials and contact in plain, precise language.
- Map endpoints to a rationale (why this endpoint, why this method, why this omission).
- Explain how chemistry, tox and clinical data will be combined in the BER.
Step 3: Review supplier and material data
Regulators are increasingly critical of unverified supplier claims. Under ISO 10993-1:2025, it’s wise to:
- Request updated material specifications and any new biocompatibility/chemistry data.
- Check for changes in raw materials, processing aids, or sterilisation compatibility that might alter biological risk.
Step 4: Align risk and quality documentation
Make sure:
- Biological risks and controls appear in the ISO 14971 risk file.
- Technical documentation, IFU/label claims and clinical evaluation are consistent with BER conclusions.
- QMS procedures (design control, change control, PMS) reference ISO 10993-1:2025 where relevant.
Step 5: Train teams and engage Notified Bodies
- Train internal teams – especially R&D, QA/RA and toxicology – on what’s changed in ISO 10993-1:2025.
- Brief your Notified Body ahead of surveillance or renewal audits if you plan a significant BER/BEP update cycle, so expectations are aligned.
Common pitfalls and regulatory findings
Across regulators and expert reports, recurring problem areas include:
- Incomplete chemical characterisation – missing extractables/leachables studies, poor analytical sensitivity, or no toxicological interpretation.
- BERs detached from risk management – conclusions that never show up in the ISO 14971 file or management review.
- Omitted endpoints with no justification – especially for long-term or high-risk devices.
- Blind trust in supplier data – no verification or critical review in light of new scientific concerns.
Prevention looks like:
- Using structured BEP/BER templates with explicit sections for risk linkage and test justification.
- Running cross-functional reviews (RA, QA, tox, clinical) before sign-off.
- Treating the BER as a living document that updates with design changes and PMS, not a one-off submission artefact.
Case Study: Implementing ISO 10993-1:2025 in practice
Imagine a Class IIb implantable device manufacturer heading into MDR surveillance in early 2026:
- Their existing BER is based on ISO 10993-1:2018, with limited chemistry and vague references to “long history of safe use”.
- Previous NB feedback has already flagged questions around sensitisation risk and incomplete justification for omitted systemic-tox tests.
They decide to align with ISO 10993-1:2025:
- Gap Assessment – identifies missing chemical characterisation, no explicit link to ISO 14971, and weak literature support.
- Updated BEP – sets out new chemical analysis per ISO 10993-18 and FDA expectations, plus a restructured justification for endpoints.(NAMSA)
- Targeted Testing – runs focused extractables/leachables and sensitisation studies instead of a broad, unfocused panel.
- Rewritten BER – integrates chemistry, toxicology and updated clinical data into a single risk narrative, with clear linkages to the risk file.
At the next MDR surveillance audit, biological safety passes without major findings. No additional animal testing is required, and the manufacturer has a clearer, more defensible biological safety story for future design changes.
Future outlook: Global alignment and next steps
ISO 10993-1:2025 is part of a broader evolution:
- ISO 10993-17:2023 tightened the approach to toxicological risk characterisation – especially for leachables and systemic exposure.
- FDA’s guidance and draft guidance continue to harmonise expectations around chemical analysis and biological evaluation methods.
- MDR, FDA and other regulators are converging on a shared idea: biocompatibility is not a static “pass/fail” event; it’s a lifecycle risk activity that must adapt as science, materials and clinical practice evolve.
For manufacturers, that means ISO 10993-1:2025 is unlikely to be the last word – but it is now the baseline. Building flexible, well-documented processes around it will make future updates far easier to absorb.
Patient Guard can help you build that flexibility – from ISO 10993 gap assessments and BER rewrites to integrated risk-management alignment under ISO 14971. Get in touch.
Wrapping up
The ISO 10993-1:2025 revision doesn’t just tweak terminology. It raises expectations for:
- Scientifically reasoned, risk-based biological evaluation.
- Deep integration with ISO 14971 and MDR technical documentation.
- Transparent, defensible BEPs and BERs that regulators can follow without guesswork.
For manufacturers, the opportunity is clear: use this biological evaluation update in 2025 as a chance to modernise your biocompatibility strategy, reduce unnecessary testing, and make regulatory interactions smoother.
If you’re ready to bring your biological evaluation in line with ISO 10993-1:2025, Patient Guard can support you with a structured ISO 10993 gap assessment, BER update plan, and full integration into your ISO 14971 risk management and MDR technical documentation. Speak to an expert today.
FAQ – ISO 10993-1:2025 and Biological Evaluation
The new edition of ISO 10993-1:2025 reinforces biological evaluation as a risk-based, lifecycle process. It strengthens alignment with ISO 14971, increases reliance on chemical characterisation (ISO 10993-18), clarifies expectations for complex and long-term devices, and tightens rules on using existing data and justifying test omissions.
Not necessarily – but you may need to update your Biological Evaluation Report (BER) if it lacks robust chemical characterisation, doesn’t integrate tox and clinical data into a coherent risk narrative, or doesn’t clearly link to your ISO 14971 risk file. Devices with material or process changes, or where regulators have previously raised biocompatibility questions, should be prioritised.
ISO 14971 provides the overarching risk-management framework; ISO 10993-1:2025 specifies how biological hazards, endpoints and evaluation must be handled within that framework. Biological risks, control measures and residual-risk conclusions from the BER must appear in the ISO 14971 risk file and be considered in PMS and management review.
A BER under ISO 10993-1:2025 should:
- Follow a pre-defined BEP;
- Summarise chemical characterisation, biological tests, literature and clinical data;
- Justify any omitted endpoints;
- Provide a clear conclusion on residual biological risk;
- Explicitly link to ISO 14971 risk management and MDR technical documentation.
Notified Bodies review your BEP, BER, risk management file, PMS and clinical evaluation together. They check that your approach follows ISO 10993-1:2025, that chemical and biological evidence is sufficient for the device’s risk class and contact type, and that residual risks are justified in line with MDR Annex I. Weak justifications, missing chemistry, or BERs that don’t link to risk management are common triggers for nonconformities.
Yes. Patient Guard can support you with ISO 10993-1:2025 gap assessments, updated BEPs and BERs, toxicological risk assessment strategies, and alignment with ISO 14971 and MDR technical documentation – helping you modernise your biological evaluation without over-testing or missing critical risks.
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