Sofia Spjuth
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The fourth edition of ISO 14155 is days from publication. Here’s what’s changing, what it means for your clinical investigations, and what to do now.
By: Sofia Spjuth
On January 28, 2026, the European Commission published Implementing Decision (EU) 2026/193, formally harmonizing the EN ISO 14155:2020/A11:2024 standard for clinical investigations with the EU Medical Devices Regulation (MDR). At the same time, the fourth edition of the standard is in its final production stages and is expected to be published within weeks, effectively replacing the newly harmonized version Almost immediately.
Since the MDR entered into force, ISO 14155 has not been formally harmonized—until now. This creates an unusual situation in which a long-waited harmonized standard will be canceled and replaced just days or weeks after achieving harmonization.
As a member of the ISO/TC 194 working group that developed this revision—and a participant in the development of the previous edition (ISO 14155:2020)—I’ve had a front-row seat to the discussions that shaped these changes. Here are three things you need to know.
1. Risk Management for Clinical Investigations Gains Long-Awaited Clarity
If you’ve struggled to apply risk management principles to your clinical investigations, you’re not alone. This was one of the most discussed topics within the working group and what accelerated the revision of the standard. Persistent industry feedback made clear that sponsors and other stakeholders found it difficult to translate the general framework of ISO 14971 into the specific context of a clinical study. The new edition addresses this with expanded guidance in the core text as well as an updated informative annex (Annex H) describing how ISO 14971’s principles apply to a clinical investigation:
Focus on investigational device risks. The updated standard clarifies that risk management shall focus on risks related to use of the investigational device, especially residual risks, and that evaluation must account for the sample size, population, and indication specific to your study. This is a welcome distinction as the rate of Adverse Device Effects (ADEs) during a clinical investigation can differ materially from post-market use in a broader population.
Clinical procedure risks distinguished from device use risks. The standard draws a clearer line between risks from the device usage and risks from CIP-required clinical procedures outside routine clinical practice. For these non-device, non-routine procedure risks, a descriptive risk assessment is generally sufficient (i.e., full ISO 14971 methodology does not apply). But remember, “routine clinical practice” may vary across regions, so multi-country studies must identify and document eventual differences.
2. Standard Takes First Stab at Estimands and Study Design Considerations
Beyond clarifying existing concepts, the new edition deliberately aligns with broader frameworks including EU MDR and ICH GCP. A notable addition is the estimand framework and a new informative annex on clinical investigation design considerations (Annex K), referencing FDA, MHRA, and ICH E9 (R1) guidance. This brings the device world one step closer to the statistical rigor long standard in pharmaceutical development—meaning study protocols better defined from the outset, with clearer treatment of intercurrent events, missing data strategies, and population-level effect estimation.
3. Clinical Events Committees Are Now in the Standard
The fourth edition introduces a new section on Clinical Events Committees (CECs)—independent committees of clinical experts established by the sponsor to ensure consistent event assessment across participating centres and mitigate inadequate reporting risks. This addition came from discussions about how multi-centre studies can suffer when different investigators characterize the same types of events differently, undermining safety data integrity.
Think of CECs as the counterpart to Data Monitoring Committees (DMCs) but focused on consistent adverse event and device deficiency classification. If you still decide to forego a CEC and/or DMC, it is important to document the rationale. If you do establish one, document conflict of interest declarations and potential bias of committee members.
What You Need to Do
The fourth edition will likely take effect without a transition period, and Notified Bodies and Regulatory Agencies will consider it gold standard from the moment it is published. Here’s how to prepare:
Conduct a gap analysis. Compare the new requirements against your current clinical investigation procedures. Focus on risk management documentation and study design practices. These are the areas with the most substantive changes.
Update your QMS. The clinical investigation portions of your quality management system will likely need revision, particularly around CEC/DMC governance and risk management requirements.
Evaluate ongoing studies. Investigations in early planning should incorporate the new requirements directly. Studies already underway may need a targeted assessment to identify gaps. Always document the rationale for actions taken or not taken.
Train your team. The changes to the standard, not at least related to risk management warrant dedicated training—not just a circulated PDF.
The Opportunity
The ISO 14155 2026 update is not just about compliance. As the standard moves closer to ICH guidelines, it creates a more navigable framework for manufacturers working across regulatory boundaries, particularly in the biotech and combination product space, where teams have long needed to reconcile device and pharmaceutical requirements.
There is also a strategic dimension. Manufacturers who adopt the new standard quickly will be better positioned with Notified Bodies, who will be looking for alignment with this edition in conformity assessments. Waiting while competitors demonstrate compliance is a risk in itself.
The working group has already begun discussing the next revision. The regulatory landscape is not standing still. Neither should you.
Need help assessing the impact of the ISO 14155 2026 update on your clinical program? Contact us for a gap analysis, implementation planning, or clinical investigation support.
About the Author
Sofia Spjuth, Vice President of Clinical Affairs, Europe at Veranex, is a medical device engineer with 10+ years of experience in the medtech industry. She is a member of SIS/TC 340 and SIS/TC 331, Technical Committees defending Swedish interests in European and global medical device standardization. Sofia is a nominated Swedish expert in ISO/TC 194 WG 4 (clinical investigations of medical devices) and participated in the development of both ISO 14155:2020 and the forthcoming fourth edition.
Clinical Research at Veranex
Clinical Research is where Veranex’s device-specific CRO depth comes to the forefront. Our teams design and execute trials for medical devices and IVDs with a clear understanding of surgical learning curves, device tracking, and ISO 14155 requirements, informed by earlier design, human factors, preclinical, regulatory, and commercial strategy work. Endpoints are selected to satisfy regulators and payers, with CSMA and Integrated Evidence Planning shaping value-oriented data strategies. Trial data feeds seamlessly into Regulatory Affairs, Medical Writing, and post-market evidence activities, including safety reporting and PMCF. With one iCRO accountable from design through follow-up, your trials support both approval and adoption.