ISO 14155: 2026 Updated Requirements for Medical Device Clinical Investigations
Diana Posa (1), Ermanno Papaleo (1)1. Iberania Contract Research20 April 2026The fourth edition of ISO 14155, the international Good Clinical Practice standard for medical device clinical investigations, has been published.
In March 2026, the International Organization for Standardization (ISO) published the fourth edition of the ISO 14155 Clinical investigation of medical devices for human subjects — Good clinical practice.
This new version replaces ISO 14155:2020 and reflects regulatory and practical experience gained several years after the EU Medical Device Regulation (MDR, Regulation (EU) 2017/745) entered into full application in May 2021.
Although ISO 14155:2020 remains the only harmonised version currently conferring presumption of conformity under the EU MDR, Notified Bodies and competent authorities are expected to consider ISO 14155:2026 as reflecting the state of the art from its publication. For ongoing studies, a focused gap assessment against the 2026 requirements is advisable to identify necessary updates, supported by clear justification where immediate full alignment is not feasible.
KEY EVOLUTION OF ISO 14155
This ISO 14155 is grounded in the principles of the Declaration of Helsinki and international Good Clinical Practice (GCP). It specifically addresses the requirements for the design, conduct, recording and reporting of clinical investigations conducted in human subjects to evaluate the clinical performance, effectiveness and safety of medical devices.
Key characteristics of the standard remain unchanged:
Protection of the rights, safety and well‑being of human subjects.
Applicability to pre‑market and post‑market clinical investigations, including PMCF studies.
Clear definition of roles and responsibilities of sponsors, investigators and other stakeholders.
However, ISO 14155:2026 introduces important updates, including clearer risk management principles, reinforced oversight structures, and strengthened scientific and statistical expectations:
Applying ISO 14971 risk management principles coherently to clinical investigations.
Defining appropriate oversight mechanisms for complex and multi‑site studies.
Ensuring consistency in event classification and safety assessment.
Addressing statistical considerations with sufficient methodological rigor.
CHANGES INTRODUCED IN ISO 14155:2026 VERSION
Terminology changes were introduced.For example, the meaning of Clinical Performance was revised to clarify clinical benefit and context of use. The term Compliance was harmonized by Conformance throughout the standard. Definitions related to Device Deficiencies, Adverse Events, and Safety Reporting were also clarified. However, although the most recent revision of the Declaration of Helsinki (2025) introduced the term Participant, this change was not adopted in ISO 14155:2026, which continues to use the term Subject.
Risk management is now more precisely scoped. Guidance on applying ISO 14971 to clinical investigations is expanded through a revised informative Annex H, with a clearer distinction between device-related risks and risks arising from protocol-mandated procedures outside routine clinical practice. For multi-country studies, Sponsors must also document differences in what constitutes routine clinical practice across regions, ensuring context-appropriate risk evaluation. The standard also introduces an explicit assessment of residual risk, improving transparency and alignment with EU MDR lifecycle expectations. Consistently, adverse events are now categorized accordingly, keeping device performance data separate from procedural complications.
Scientific and statistical rigor is strengthened methodological expectations, particularly in relation to alignment between study objectives, hypotheses and endpoints, with clearer expectations on non-inferiority margins and missing data handling. Three study design types are now outlined as exploratory, confirmatory or observational clinical investigations. There are also increased requirements for an improved statistical transparency for analysis planning. A new informative Annex K consolidates study design considerations and describes the framework in detail.
Governance and oversight are more formally structured. Clinical Events Committees are introduced as a recognized governance component to ensure consistent, unbiased clinical event adjudication across sites. Their inclusion reflects widespread recognition that investigator‑level variability can compromise data credibility and scientific robustness, especially in multi-center studies. Data Monitoring Committees receive a clearer role, including responsibility for suspension or stopping conditions, and their absence must now be explicitly justified. Dedicated articles on suspension and premature termination provide a more harmonized process than previous editions.
Ethical and subject protection requirements are also reinforced. Subjects must be explicitly given the opportunity to discuss participation with family members or trusted persons, and protections are broadened to include users and other persons involved in the investigation. Follow-up and continued care obligations are clarified, including care that may differ from routine clinical practice. This aspect carries significant logistical and financial implications and warrants early planning by sponsors.
The full implications of ISO 14155:2026 will become clearer as sponsors, notified bodies, and regulators begin applying it in practice. What is already evident is that early adoption rewards those who invest in cross-functional expertise, including clinical, statistical, and regulatory, to navigate the new expectations around estimands, risk management, and governance.
The standard raises the ceiling and at Iberania CRO, we support organizations in implementing the full scope of ISO 14155:2026 in a practical and compliant manner.
Reach out if you have any questions!