The International Standard Organization (ISO) has released the fourth edition of the International Good Clinical Practice standard for medical device investigations. This long-awaited publication of approved guidance on “Clinical Investigation of Medical Devices for Humans” came into effect on April 26, 2026. It replaces ISO 14155:2020 with no transition period. This means that the requirements are in effect already.

• What are the top six changes?
• What does this mean for teams?

What are the top six changes?

Version 4 sets new requirements for sites, sponsors/investigators for risk management, clinical events committees (CEC), data monitoring committees (DMC), study design and statistics, informed consent, and subject protection and adverse event reporting.

1. Risk management: Version 4 of ISO 14155:2026 directly addresses application of risk management principles. There are two categories of risk: risks related to device use and risks from non-routine clinical procedures. The latter now requires only a descriptive risk assessment and the full ISO 14971 methodology does not apply to these.
2. Clinical events committees (CECs): These are newly introduced in an entire section called “Clinical Event Committees.” These are independent committees of clinical experts established by the sponsor to ensure consistent event assessment across all participating sites.
3. Informed consent: There are a cluster of changes around informed consent and subject protection content within the guidance. There are many sections that have been strengthened and clarified, such as eligibility, consent subject withdrawal, health data handling, and the clearness of participant information. The documentation related to consent needs to be reviewed against the revised requirements.
4. Adverse event reporting: When a rationale for a more proportionate approach to adverse event collection and reporting is defined in the clinical investigation protocol (CIP), certain adverse events may be exempted from collecting or reporting requirements. This is seen in the new guidance available in ICH. This option is not considered as the lowering of a standard, but rather as an efficient method of application.
5. Data monitoring committees (DMCs): Essentially, DMCs should exist. The conditions under which a study would be stopped or suspended must be documented by a DMC. If there is no DMC, the absence of one must be “formally justified” and documented with solid rationale.
6. Statistics and study design: There is a new Annex K, which references clinical investigation design guidance, including ICH E9(R1) for an estimated framework. The investigation protocol should have clear instructions on missing data, intercurrent events, and how the selected population relates to intended use population.

What does this mean for teams?

• Quality Management Systems (QMS) need to be updated. Any procedures, templates, or Standard Operating Procedures (SOPs) that reference the 2020 edition need to be revised.
• New requirements should be incorporated and documentation is required. The new requirements should be incorporated into new studies, while ongoing studies that bridge the time between version 3 and version 4 do require documentation of a gap assessment and possible a change plan.
• Training is essential. Teams needs to have basic medical device training, training on the new versions of ISO 14155:2026 and ISO 14972:2019. The risk management components are substantial and these documents are a pair to be considered together, much like ICH E6(R3) and ICH E8(R1).
• Copies of ISO documents are required. Teams will need copies of ISO 14155 and the accompanying ISO 14971, which can be purchased on the ISO website.