The FDA officially recognized EN ISO 10993-1:2025 – “Biological evaluation of medical devices – Part 1: Requirements and general principles for the evaluation of biological safety within a risk management process” on Monday, May 25, 2026. However, the Agency granted only a partial recognition!
The 6th edition of ISO 10993-1 has been reshaped with a stronger focus on risk estimation, aligning it closely with ISO 14971-Application of risk management to medical devices. For manufacturers, implementing ISO 10993-1:2025 requires a documented approach. The standard now demands that manufacturers evaluate the medical device throughout its entire lifecycle and analyze all device exposure scenarios in greater depth as part of the overall risk management process.
The FDA will accept declarations of conformity for pre-market submissions based on ISO 10993-1:2018 until July 1, 2029. After this date, declarations of conformity will be accepted exclusively based on ISO 10993-1:2025, while taking certain observations into account.
Specifically, the following parts of the standard are not recognized by FDA:
Clause 6.5.11.3 of EN ISO 10993-1:2025: “consumer products”
The point in relevant to the definition of consumer products. In the FDA Guidance on the Use of ISO 10993-1:2018 (2023), Attachment G: Biocompatibility of Certain Devices in Contact with Intact Skin, the Agency recognizes that many intact skin-contacting devices are composed of synthetic polymers or natural fabrics with a long history of safe use. The FDA considers such materials to pose a very low biocompatibility risk, supporting a least burdensome approach in premarket submissions. This approach allows for the submission of specific material information instead of new biocompatibility testing when certain conditions are met, thereby aligning with the 3Rs principle (Replace, Reduce, Refine) to minimize animal testing.
The FDA only partially recognized the newly published EN ISO 10993-1:2025. The Agency has noted that the phrase consumer products as used in the standard conflicts with Attachment G of the FDA’s 2023 Biocompatibility Guidance. Specifically, demonstrating that a material is used in a consumer product with skin contact (as per 6.5.11.2 of EN ISO 10993-1:2025) does not automatically satisfy requirements for bypassing biocompatibility testing.
According to this guidance, devices contacting only intact skin for any duration (limited, prolonged, or long-term) may be eligible for this streamlined assessment if composed of materials listed in the FDA policy. Relevant polymers include, among others, ABS, PC, POM, silicone, PE, PET, PA, PUR, PTFE, and their blends. Not all materials in consumer products are included in Attachment G of the guidance.
Clause 6.9 of EN ISO 10993-1:2025: Biological risk estimation
The FDA states that this clause conflicts with Sections 5.5, 6, and 7 of ISO 14971:2022 (Medical Devices — Application of Risk Management to Medical Devices), which address
- Risk Estimation: For each identified hazardous situation, the manufacturer shall estimate the associated risk using available information or data.
- Risk Evaluation: for each hazardous situation it should be estimated of the risk is acceptable or not using the criteria for risk acceptability defined in the risk management plan.
- Risk Control: measures that are appropriate for reducing the risks to an acceptable level
Risk estimation incorporates the analysis of the probability of occurrence of an harm and the severity of the harm.
For both standards, to reach a proper biological risk estimation, qualitative or quantitative values should be assigned to the severity and probability of occurrence of biological harm.
According to ISO 14971:2019, the risk management plan defines the criteria for risk acceptability, since reviewers check compliance by inspecting the risk management file. According to EN ISO 10993-1:2025, Biological risk estimation is an input to determine biological safety. Acceptability criteria are defined in the biological evaluation plan and ISO 14971 serve as guidance to develop them. Therefore, because risk estimation alignment between the standards may differ, the FDA will require submissions to rely directly on the ISO 14971 framework.
Genotoxicity evaluation
In addition, FDA notice that, Table 1-4 of EN ISO 10993-1 add the evaluation of genotoxicity for all prolonged-contact devices, except for those that come into contact with intact skin only (Clause 6.5.7 of ISO 10993-1:2025).
In fact, ISO 10993-1 6th edition outlines different recommendations for genotoxicity evaluation for medical device categories with the same contact duration. Exposure to a genotoxic chemical increases the risk of cancer development. When exposure is systemic, a genotoxic chemical can reach multiple tissues, increasing the risk, consequently, more medical devices will require genotoxicity assessment. The authors added a genotoxicity evaluation for medical devices contacting mucosal membranes, breached or compromised surfaces, and in direct contact with circulating blood.
In accordance with ISO 10993-1:2025, if a prolonged-contact MD presents systemic toxicity, then it must also be addressed as genotoxicity. Regardless of duration, this could affect any device in contact with circulating blood.
As noted by FDA this is not aligned with Table A.1 of the FDA guidance (2023). Therefore, the implementation of these requirements in accordance with EN ISO 10993-1:2025 might not be necessary for the biological evaluation of your medical devices.
What does FDA suggest?
A technical working group responsible for the systematic approach to biological evaluation and terminology (ISO TC194 WG1) within the broader ISO/TC 194 committee (which governs the clinical and biological evaluation of medical devices) is developing technical reports on the application of ISO 10993-1:2025. It covers topics such as:
- intermittent contact
- bioaccumulation,
- reasonably foreseeable misuse,
- and application throughout the medical device life cycle
Therefore, discussion for the implementation of these requirements to proceeding with the biological evaluation in alignment of risk estimation, of a MD is a suggested valuable strategies by FDA.
ToxHub comprises a specialized team dedicated to ensuring the safety and regulatory compliance of medical devices. Our toxicologists possess extensive experience in medical devices’ toxicological risk assessments. They offer the required expertise in regulatory compliance and are available to provide technical and specialized consultancies to ensure the success in MDs products development.
Issued by Eleonora Pace