In recent months, the regulatory framework governing the biological safety of Medical Devices has undergone a significant evolution. With the publication, in November 2025, of the new edition of ISO 10993-1 – the reference standard for biological evaluation – a shift in perspective already underway has been further reinforced: no longer an approach based on a list of tests to be performed, but rather a structured process driven by risk management.

This update was followed, in April 2026, by the new editions of ISO 10993-6 and ISO 10993-7, which respectively update testing for local effects after implantation and the evaluation of ethylene oxide residues. During the same period, ISO 14155:2026, dedicated to clinical investigations, was also updated.

Taken together, these revisions mark a significant transition toward a more modern, coherent, and integrated system. Biological and clinical safety can no longer be addressed as isolated activities or limited to the initial development phase. On the contrary, they must be managed as continuous processes accompanying the medical device throughout its entire lifecycle.

From design to the clinical phase and through post-market surveillance, every decision must be supported by a robust and continuously updated risk assessment, based on data, scientific evidence, and device knowledge. This approach enables more targeted evaluations, reduces unnecessary testing and, above all, improves the overall level of patient safety.

1. ISO 10993-1:2025 – Main changes in the framework standard

The methodological evolution is driven by the framework standard ISO 10993-1, published in its 2025 edition. The standard revises the fundamental requirements, formalizing the transition from a prescriptive approach based on test execution to a biological evaluation process integrated into the risk management system in accordance with ISO 14971. Compared to the 2018 version, the new edition introduces significant changes, including:

• New standard title: the title changes from “Evaluation and testing within a risk management process” to “Requirements and general principles for the evaluation of biological safety within a risk management process”. The title explicitly reinforces an approach based on general principles of biological safety rather than solely on the execution of tests.
• Alignment with ISO 14971: harmonization of terminology and structural integration of biological evaluation into the risk management process.
• Characterization and hazard identification: greater emphasis on material characterization and systematic identification of biological hazards and related hazardous situations.
• Estimation of biological risk: evaluation based on the combination of identified hazards and patient exposure, in line with the risk estimation principles of ISO 14971.
• Replacement of Table A.1: the previous single matrix has been replaced by four separate tables based on the type of contact, focusing on biological effects to be considered and on a more targeted selection of endpoints.
• Role of physicochemical information: no longer treated as biological effects, but as essential elements for hazard identification and risk assessment.
• Devices already on the market: stronger emphasis is placed on the use of existing data and scientific justification; tests are not automatically required to be repeated, provided that biological risk is adequately assessed and documented on the basis of available and updated evidence.

New criteria for exposure calculation

Within the framework standard, the method for determining the duration of contact with the device has been refined by introducing an approach based on actual exposure and the so-called “contact days”, with possible impacts on device classification:

• Repeated or continuous contact: in cases of use on consecutive days, exposure duration is evaluated by considering the calendar days between the first and the last use. Under this logic, devices used for limited periods but on a daily basis (e.g., CPAP devices used for a few hours per day) may fall within prolonged or long-term contact categories.
• Intermittent contact: where use is separated by significant intervals (typically equal to or greater than 24 hours), exposure duration may be determined on the basis of actual contact days only, requiring case-by-case assessment.
• Reasonably foreseeable misuse: determination of contact duration and modalities must also include scenarios of “reasonably foreseeable misuse”, which may alter biological exposure and influence subsequent risk assessment.

The concept of “reasonably foreseeable misuse”, derived from ISO 14971, is explicitly integrated into ISO 10993-1:2025 and must be considered from the biological evaluation planning phase (Biological Evaluation Plan). It contributes not only to the definition of exposure scenarios, but also to the identification of biological hazards and risk estimation, potentially affecting contact duration and modality and, consequently, device classification and the selection of biological effects to be evaluated.

2. Laboratory Testing – what changes in ISO 10993-6 and ISO 10993-7

The specific parts of the ISO 10993 series define the test methods and evaluation criteria to be applied for biological safety characterization purposes. The revisions published in April 2026 introduce relevant methodological updates and, although not yet formally recognized by the FDA, are already considered “state of the art” references in regulatory evaluations:

• ISO 10993-6:2026 (Local effects after implantation): updates methods for evaluating local tissue response, introducing the new Annex E relating to testing on peripheral nerve tissues and strengthening the guidance provided in Annex G for histopathological evaluation.
• ISO 10993-7:2026 (Ethylene oxide residues): introduces a more structured and risk-based approach for evaluating the safety of EO-sterilized devices, with expanded Annexes F and G and updated methodologies for residue determination and patient exposure estimation, also according to the target population and duration of use.

3. Clinical Investigations – What Changes in ISO 14155:2026 (Clinical Trials)

The fourth edition of the standard on Good Clinical Practice (GCP) for Medical Devices replaces the 2020 version with immediate applicability and no transition period, introducing a significant strengthening of the risk-based approach and governance:

• Risk management: the standard clarifies the distinction between residual risks associated with the use of the investigational device and risks deriving from clinical procedures required by the Clinical Investigation Plan (CIP) but not belonging to routine clinical practice. For the latter, a descriptive approach to risk evaluation is introduced, distinct from the ISO 14971 logic applied to the device.
• Trial governance: the role of independent committees established by the sponsor is formalized. CECs (Clinical Events Committees) ensure consistent and independent classification of clinical events; DMCs (Data Monitoring Committees) require the definition and documentation of criteria for study suspension or termination. The decision not to establish a DMC must now be formally justified.
• Design and reporting: the new Annex K has been introduced (for alignment with FDA guidelines, MHRA guidance, and ICH E9 statistical principles), and procedures and timelines for adverse event (AE) reporting have been strengthened.

Operational impact

Manufacturers should perform a gap analysis of existing Technical Files and adapt their Quality Management System (QMS) to the latest regulatory expectations.

>>> Complife Group offers strategic-regulatory consulting and advanced testing and validation services throughout the entire product lifecycle. From the definition of the Biological Evaluation Plan to laboratory operations, Complife experts support manufacturers in ensuring compliance with the latest ISO standards.

SOURCE:
ISO 10993-1:2025
ISO 10993-7:2026
ISO 14155:2026
ISO 10993-6:2026
Complife Group, Biocompatibility Morning, Bologna, 20 maggio 2026, materiali evento.