The 2025 revision of ISO 10993-1 introduces a more structured lifecycle approach to the biological evaluation of medical devices by aligning it closely with ISO 14971 risk management principles. Biological evaluation is now expected to be a continuous process, with risk estimation and evaluation implemented at every stage from early design to post-market surveillance.
While some changes relate to terminology and emphasis, ISO 10993-1:2025 also has several practical implications for medical device manufacturers. These include possible device re-categorization and additional testing requirements, particularly with regard to genotoxicity and carcinogenicity evaluation.
Prioritization of in vitro methods and reduction of animal testing
The new version of ISO 10993-1 places even greater emphasis on animal welfare than the 2018 edition, promoting a risk-based approach that limits in vivo testing to cases where it is strictly necessary. Animal tests should not be performed unless no suitable alternative methods are available and unless they are essential to demonstrate biological safety.
It is worth noting that regulatory authorities such as the FDA may still require certain tests to be performed in vivo, even when in vitro alternatives are outlined in the relevant ISO 10993 standard. Examples include sensitization and irritation (ISO 10993-10 and ISO 10993-23), for which the FDA does not currently consider in vitro methods as equivalent.
Changes to device categorization
In the previous version of ISO 10993-1, medical devices were categorized as surface, externally communicating, or implantable, in addition to their contact-site-specific designation. In the newest version, devices are categorized only based on contact type:
Intact skin
Intact mucosal membranes
Breached or compromised surface or internal tissues (other than blood)
Blood
Exposure duration is also defined more clearly in ISO 10993-1:2025, particularly with respect to the “total exposure period” accumulated over multiple uses of the same device. Reusable devices are categorized based on the total exposure time rather than exposure from a single use, which may lead to re-categorization into different duration classes and therefore influence the extent of biological evaluation required.
Reasonable foreseeable misuse
The new version of ISO 10993-1 requires manufacturers to consider “reasonably foreseeable misuse,” which is not intended by the manufacturer but can result from intentional or accidental, “readily predictable human behavior.” If such misuse is likely to result in longer exposure times or contact with other than intended sites, this must be considered when selecting the biological risks that need to be evaluated.
Changes to biological evaluation matrix tables and effects to be evaluated
The main evaluation matrix, formerly presented in Table A.1 of ISO 10993-1:2018, has been split into four separate tables in the 2025 version. Each table details the biological effects (formerly “biological endpoints”) to be evaluated for devices belonging to different contact categories.
Changes to evaluation requirements for specific biological effects include:
Extension of genotoxicity testing requirements. A genotoxicity evaluation is now required for all medical devices with prolonged (>24 h–30 d) or long-term (>30 d) contact with all tissues except intact skin. Previously, this was not consistently recommended for all prolonged-contact devices contacting mucosal membranes, breached or compromised surfaces, or having indirect blood contact.
Extension of carcinogenicity evaluation requirements to devices in long-term contact with intact mucosal membranes.
Removal of material-mediated pyrogenicity from Tables 1–4. Rather than a checkbox requirement, it is now treated as a separate consideration.
Consolidation of acute, subacute, sub-chronic, and chronic systemic toxicity columns into a single systemic toxicity column. The extent of the evaluation should reflect the duration of exposure to the device.
Replacement of “implantation effects” with “local effects after tissue contact”, acknowledging that it may be necessary to assess local tissue responses for non-implantable devices.
Are new tests required?
Many medical devices will be categorized differently following the ISO 10993-1:2025 update. Devices already on the market do not automatically require new testing; however, manufacturers are expected to review previous biological evaluations and document that they remain valid in light of the updated risk-based approach and revised exposure duration criteria. If gaps are identified, for example, in the form of missing genotoxicity information for devices with prolonged or long-term contact, additional testing may be required.
If additional testing or updates to the Biological Evaluation Plan (BEP) are needed, Measurlabs is here to help. With a comprehensive range of ISO 10993 testing services and extensive experience in ensuring that medical devices comply with regulatory expectations, we are well-equipped to support manufacturers in adapting to the ISO 10993-1 update.