Strengthening Biological Evaluations

The Evolving Expectations for Biological Evaluation Reports

A practical guide to building biological evaluation reports (BERs) that survive notified body review. Leading with science, aligned with ISO 10993-1:2025 and tied into your risk management. 

Notified Bodies (NBs) have raised the bar on biocompatibility. Under EU MDR 2017/745 and IVDR 2017/746, technical reviewers now expect a chemistry-led BER, defensible toxicological risk assessment, and alignment with the latest standards. If your BER still leans on animal testing, read-across or a results table with conclusions simply asserted, expect deficiencies. 

Here is a quick snapshot of what reviewers look for now, and where manufacturers often fall short, for both new devices and products already on the market. 

1. Lead with Chemical Characterisation

Notified Body reviewers are increasingly expecting to see a thorough chemical characterisation to anchor the whole biological evaluation, rather than defaulting to a battery of biological tests. Your Biological Evaluation Plan should clearly define the approach for characterisation, equivalence and testing. BERs that rely on historically depended on animal testing or read‑across draw scrutiny unless underpinned by rigorous extractables and leachables (E&L) data characterising all relevant constituents, impurities, degradation products, and processing residues.  Chemistry drives the strategy, and any decision not to characterise a material needs its own justification. 

Key Takeaway: Make E&L data the backbone of your BER, and justify every gap.

2. Toxicological Risk Assessment (TRA) Rigour and Authorship

Every compound reported above the Analytical Evaluation Threshold (AET) should be carried into a documented TRA, with defensible tolerable intake and exposure limits, credible data sources (and a clear hierarchy when data is sparse), and conservative handling of unidentified or non-target compounds. Reviewers want transparent reasoning trail rather than a results table with conclusions asserted.  They want to see evidence that the author is suitably qualified. A CV or peer-reviewed paper is accepted; a LinkedIn profile generally is not! The same expectation applies wherever you claim equivalence in place of testing or a justification. 

Key Takeaway: Show your working, and show your author’s credentials. 

3. Transition to ISO 10993-1:2025

The 2025 revision of ISO 10993-1 tightens up expectations on chemical characterisation, risk-based justification and data integration, and NBs are aligning to it. A BER built to the 2018 edition which successfully passed previous reviews may now prompt gap questions. Treat “State of the Art” as a moving baseline you are expected to track and address, even where harmonisation status lags, it can sometimes take 1-3 years for new versions of standards to become harmonised. Keep technical documentation up to date with State of the Art, make sure all updated standards and requirements are captured in all of the documentation.  Failure to assess the impact of the update to ISO 10993 and make the required updates could end up as a non-conformance in surveillance or re-certification audits.  

Key Takeaway: Run a 2018-2025 gap analysis now, and plan to implement the required updates it identifies.

4. Justify CMR  and Endocrine Disruptor Substances… Properly

For substances above 0.1% w/w that are CMR 1A/1B or endocrine-disrupting, NBs expect a full benefit-risk justification under GSPR 10.4.2 and the SCHEER guidance, including a documented analysis of alternative materials, designs or treatments and why they were rejected. Cost alone is not an acceptable reason for rejection. Expectations have broadened beyond classic phthalates (e.g. DEHP) to a wider watchlist, and labelling obligations are checked. Evaluations must reflect the device in its final finished and sterilised state, capturing the influence of processing aids, mold-release agents, adhesives, coatings, sterilisation residues (e.g. Ethylene Oxide/Ethylene Chlorohydrin ) and degradation products. Many manufacturers only focus on the materials their device is made from and do not consider the impact these substances, or products in their BER. Changes in suppliers, components, sub-components or processing should always be assessed to capture if a re-evaluation is needed. 

Key Takeaway: Work with suppliers to evaluate whether CMR or endocrine disruptor substances are present and document any benefit-risk justifications for any substances above 0.1%.

5. Real Integration with ISO 14971 Risk Management

A recurring deficiency is a BER that sits in isolation. NBs now expect the biological evaluation to feed directly into, and be traceable to, the risk management file.  All biological hazards identified, risk controls, residual risk acceptance and benefit-risk all linked.  Worst case clinical or use exposure should also be realistic and consistent with the dose and exposure assumptions (contact duration, number/frequency of devices per patient, invasiveness, paediatric or vulnerable populations). Post-market biological feedback and complaints must run through your risk management process to decide whether further testing or material changes are needed on an ongoing basis in line with PMS process requirements. 

Key Takeaway: Your BER should read as part of one coherent safety case, not a standalone test report. 

How to Future-Proof Your Biological Evaluation Report

Biocompatibility evaluation now demands a far more comprehensive, transparent and scientifically defensible approach than many have been used to. Plan in advance for chemistry-led characterisation, rigorous toxicological assessment, realistic exposure assumptions, robust equivalence rationales and genuine integration with risk management, and do not overlook CRM and endocrine-disruptor justifications where they are needed or post-market biological review. Get these right, and your BER will withstand NB scrutiny and demonstrate a coherent, comprehensive, risk-based safety case for your device.

References

• ISO 10993-1:2025 – new foundations for biological evaluation under the MDR – Pure Clinical
• ISO 10993-1:2025 – What’s New in Biological Evaluation – PatientGuard
• ISO 10993-1:2025 Updates – Top 10 Essentials – NAMSA
• Reliable Toxicological Risk Assessment for E&L in the USA and Europe – SciQra
• Phthalates in Medical Devices: European Regulatory Requirements – NAMSA
• SCHEER Updates Guidance on Phthalates in Medical Devices – Emergo by UL
• ISO 10993 Biocompatibility Testing: The Complete Guide – MedDeviceGuide

Disclaimer. The views and opinions expressed in this article are solely those of the author and do not necessarily reflect the official policy or position of Test Labs Limited. The content provided is for informational purposes only and is not intended to constitute legal or professional advice. Test Labs assumes no responsibility for any errors or omissions in the content of this article, nor for any actions taken in reliance thereon.