ISO 10993-1 Revision Highlights

Part 3: Biological Effects

The sixth edition of ISO 10993-1(2025) introduces significant updates that align biological risk evaluation for medical devices with ISO 14971 risk management principles; manufacturers are now required to systematically identify biological hazards, hazardous situations, and potential biological harms associated with their devices. Biological risk estimation requires consideration of both physical and chemical properties of the device and its components. The process involves assessing exposure and estimating risks, followed by implementing effective risk control measures to mitigate or eliminate identified risks.

The standard now requires manufacturers to consider not only the intended use but also reasonably foreseeable misuse, reflecting predictable human behaviors (please refer to Highlights Part 1). Such scenarios may influence biological exposure and associated risks. The 10993-1:2025 edition replaces the term “biological endpoints” with “biological effects”, with relevant biological effects identified based on the type of device contact and exposure duration (refer to Part 2 Highlights). The previous single matrix table has been separated into four distinct tables, each corresponding to different tissue contact categories.

Core biological effects or the “Big Three” – cytotoxicity, sensitization, and irritation – remain universally applicable to all medical devices, regardless of contact category or duration. However, a substantial revision is the removal of the requirement for material-mediated pyrogenicity testing across all device categories.

Following is a summary of sixth edition biological effects updates:

Material-mediated pyrogenicity

Consensus among global testing laboratories and regulators confirms that material-mediated pyrogenicity is rare. Consequently, this test is no longer generally required; pyrogenicity evaluation is now limited to devices containing materials previously linked to pyrogenic responses or those with unknown pyrogenic potential (such as novel materials).

Genotoxicity

A genotoxicity evaluation is now a consideration for medical devices contacting mucosal membranes, breached or compromised surfaces, or those with indirect blood contact. This requirement applies to all devices with prolonged use, except those contacting only intact skin. Devices with limited-duration contact with circulating blood require evaluation of genotoxicity if they are implantable or part of an extracorporeal circuit.

Implantation

The term “implantation” has been updated to “local effects after tissue contact” to better clarify that some non-implanted devices are also recommended for evaluation of this biological effect.

When testing is determined to be necessary, studies can be designed to estimate risks of biological harms related to local tissue effects as well as to assess medical device performance or other biological effects  such as systemic toxicity or hemocompatibility, depending on the device’s intended use.

Systemic toxicity

The sixth edition consolidates previously separate categories – acute, subacute, sub-chronic, and chronic – into a single systemic toxicity effect. Toxicity testing should correspond with the device’s duration of use and include appropriate intermediate endpoints as necessary.

Carcinogenicity

Carcinogenicity evaluation is now a consideration for medical devices with long-term mucosal contact. It remains rare for carcinogenicity tests to be performed for medical devices. Thorough chemical characterization and subsequent toxicological risk assessment are emphasized to support carcinogenicity evaluation.

In summary, the sixth edition of ISO 10993-1 introduces significant changes in terminology, removes material-mediated pyrogenicity requirements, and refines genotoxicity and carcinogenicity evaluation for certain devices. These updates aim to enhance patient safety and provide greater flexibility in study design, ensuring that biological evaluations are tailored to the unique characteristics and intended uses of each medical device.

MED Capabilities

MED Institute provides comprehensive biological risk assessment services to support the safety evaluation of medical devices in accordance with ISO 10993 and related regulatory requirements. Our multidisciplinary team of professionals offers expert guidance on material characterization, biological equivalence assessment, toxicological evaluation of chemical constituents, and even support in responding to submission deficiencies. MED Institute’s technical experts have extensive experience in developing biological evaluation plans and biological evaluation reports in compliance with global regulatory standards and based on sound scientific principles. By engaging with our team of experts, several manufacturers have designed safer products and accelerated their regulatory submissions and successful market entry.

Contact us today to discuss your project needs 855.463.1633 | askmed@medinstitute.com | medinstitute.com.