ISO 10993-1:2025 – The End of Box-Ticking Biocompatibility Assessments

ISO 10993-1:2025 Changes at a Glance
Biological Evaluation Is Now Fully Integrated with Risk Management
Reasonably Foreseeable Misuse Is Now Explicitly Within Scope
Exposure Assessment Has Been Refined
The Annex A Matrix Has Been Replaced
Material and Chemical Characterisation Take Centre Stage
Continued Push to Reduce Animal Testing
What about FDA?
What Should Manufacturers Do Now?
What Does The Future Hold?

Abingdon Analytical is a dedicated, independent test house service provider to the in vitro diagnostics (IVDs) and medical devices industry. Laboratory Manager, Baranse Ozturk shares first-hand insights into the evolving biocompatibility landscape, alongside the updates to the ISO 10993-1:2025 standard. In this article, she shares her views on the standard that is now in effect and what needs to change in evaluation practices.

ISO 10993-1:2025 Changes at a Glance

The landscape of medical device biocompatibility assessment is developing. The updated ISO 10993-1:2025 standard, published in November 2025, now partially recognised by FDA, represents one of the most significant updates to biocompatibility standards in recent years. Rather than prescribing a fixed battery of tests, the revised standard reinforces a risk-based, scientifically justified approach aligned with ISO 14971, the international standard for medical device risk management.

For IVD and medical device manufacturers, this is not just a routine update. It changes how biological safety should be evaluated, documented, and justified; and the shift is most consequential for new regulatory approval submissions and post-market reviews.

Importantly, the ISO 10993-1:2025 standard itself does not require re-testing of devices already on the market with established, acceptable safety profiles. However, if your Biological Evaluation Plans (BEPs) and Biological Evaluation Reports (BERs) are still based on the 2018 version of the standard, now is the time to review your approach…

Biological Evaluation Is Now Fully Integrated with Risk Management

Biological safety is no longer treated as a standalone activity. ISO 10993-1:2025 requires clear traceability between hazard identification, risk assessment, risk controls, and residual risk acceptability. This is the same framework manufacturers already apply under ISO 14971 for mechanical, electrical, software, and usability risks.

In practice, passing biocompatibility tests alone is unlikely to constitute a complete regulatory argument. Reviewers increasingly expect to see biological risks managed within a coherent risk management file, with a documented rationale for why each evaluation approach was chosen and what the residual biological risk conclusion is.

It is worth noting that the FDA specifically excluded Clause 6.9 (Biological Risk Estimation) from its recognition of ISO 10993-1:2025, because this clause introduces a risk scoring methodology that conflicts with the established risk management framework under ISO 14971:2019. For FDA submissions, biological risks must be addressed within the ISO 14971 risk management file, not through a separate Clause 6.9 scoring approach.

Reasonably Foreseeable Misuse Is Now Explicitly Within Scope

The new standard explicitly requires biological evaluations to consider how devices may realistically be misused in practice, not just how they are intended to be used. This includes use outside of intended anatomical sites, incorrect or repeated use, reprocessing outside validated instructions, and real-world environmental conditions such as heat, moisture, or perspiration that may alter chemical exposure from the device.

This requirement broadens the scope of biological risk assessment considerably and encourages manufacturers to evaluate the actual conditions under which devices may be used throughout their lifecycle.

Exposure Assessment Has Been Refined

The way exposure duration is calculated has been updated to more accurately reflect real-world contact patterns. The 2025 revision introduces more precise exposure-duration calculation rules, incorporating concepts such as daily contact, total exposure period, intermittent contact, and repeated exposure over time. These rules are more detailed than a straightforward substitution of one metric for another and manufacturers should review the standard directly for their specific device type and use scenario.

Depending on the device, the refined calculation approach can affect exposure categorisation, and, in turn, which biological endpoints require evaluation and the supporting evidence needed to demonstrate safety. This is particularly relevant for devices used intermittently or repeatedly over extended periods, where previous approaches may have understated cumulative exposure.

The Annex A Matrix Has Been Replaced

The familiar Annex A “checklist” testing matrix has been restructured rather than simply removed. Much of the previous content has moved into the normative body of the standard, where biological evaluation requirements now sit alongside risk management expectations. Annex A itself has been refocused on material selection and characterisation, while Annex B explains the changes introduced to the contact-specific biological effects tables.

The updated ISO 10993-1:2025 Annex A and Annex B tables are organised according to the nature of body contact – intact skin, mucosal membranes, breached or compromised surfaces, and blood-contacting devices – rather than broad device categories. Endpoint selection must now be justified scientifically for each contact type, not selected from a single matrix. Devices with multiple contact modes may require separate biological effects analyses for each interaction pathway.

Material and Chemical Characterisation Take Centre Stage

The 2025 revision to the ISO 10993 standard places significantly greater emphasis on documented material understanding and chemical characterisation as the foundation of biological evaluation. Generic statements such as “the material has a history of safe use” are less likely to satisfy a thorough regulatory review on their own. Instead, manufacturers are expected to provide structured scientific justification supported by material composition data, extractables and leachable information, toxicological risk assessments, and structured gap analyses for any material, supplier, manufacturing, sterilisation, or process change.

Any change to a material or process should be evaluated for its potential biological impact and documented within the risk management framework.

Continued Push to Reduce Animal Testing

The 2025 revision strengthens support for the 3Rs principle – Replace, Reduce, and Refine. Manufacturers are encouraged to leverage chemical characterisation, toxicological risk assessments, existing scientific literature, and in vitro testing methods before considering animal studies. The emphasis is on generating scientifically robust evidence while minimising unnecessary animal testing wherever suitable alternatives exist.

A well-structured, risk-based argument grounded in chemical characterisation and in vitro data is not only scientifically preferred, it is also the approach regulators are increasingly expecting to see.

What about FDA?

ISO 10993-1:2025 is partially recognised by FDA, not fully adopted – and manufacturers should understand what that means in practice. On 25 May 2026, the FDA officially recognised ISO 10993-1:2025 (Recognition No 2-313), signalling a transition towards greater alignment with the risk-based framework. However, two specific clauses are excluded: the phrase “consumer products or” in Clause 6.5.11.3, which conflicts with Attachment G of FDA’s 2023 Biocompatibility Guidance, and Clause 6.9 Biological Risk Estimation, which conflicts with ISO 14971:2019. A full Declaration of Conformity to the standard without caveats is therefore not possible for FDA submissions.

There is also an important practical issue for manufacturers targeting both EU and US markets. ISO Tables 1 to 4 require genotoxicity evaluation for all prolonged contact device categories, whereas FDA’s Table A.1 does not require it for all such categories. Manufacturers should verify genotoxicity testing requirements against FDA guidance, not just the ISO tables, before proceeding, and should consider a pre-submission (Q-Submission / Q-Sub) meeting with FDA where there is any uncertainty.

On transition timelines, declarations of conformity to ISO 10993-1:2018 will continue to be accepted by FDA until 1 July 2029, after which the 2025 edition must be referenced. FDA’s existing published guidance and terminology remain in place during this period, so manufacturers should treat this as an evolving alignment rather than a wholesale switchover.

What Should Manufacturers Do Now?

If your current biological evaluation approach is based on ISO 10993-1:2018, a structured gap assessment is the logical next step. The standard itself does not require re-testing of devices already on the market with established, acceptable safety profiles – the focus is on ensuring that documentation, rationale, and risk management files reflect the updated framework.

Key areas to review include:

• alignment with ISO 14971 risk management files
• exposure assessment methodology against the refined calculation rules
• endpoint selection justification against the new contact-specific tables
• material and chemistry evidence packages
• change control processes that trigger biological impact assessment and
• overall biological risk rationale.

For FDA submissions, manufacturers should also address how the two excluded clauses (6.5.11.3 and 6.9) are handled and verify genotoxicity testing requirements against FDA’s Table A.1.

What Does The Future Hold?

The transition to ISO 10993-1:2025 is less about wholesale re-testing and more about a demonstrable shift: from test-driven compliance to scientifically justified, risk-based biological evaluation. Manufacturers who begin reviewing their approach now will be better placed to demonstrate alignment with the updated framework, respond to Notified Body and regulator questions, and reduce the risk of avoidable delays later in the development cycle.

Need support navigating ISO 10993-1:2025? At Abingdon Analytical, we help IVD and medical device manufacturers assess the impact of ISO 10993-1:2025 on biological evaluation programmes, identify compliance gaps, and develop risk-based evidence packages that meet evolving global regulatory expectations. Get in touch with the Abingdon Analytical team to explore how our expertise can support your biocompatibility programme: [email protected]