ISO 14155:2020 — Clinical investigation of medical devices
ISO 14155:2020 'Clinical investigation of medical devices for human subjects — Good clinical practice' is the device-world equivalent of ICH E6 GCP. It sets sponsor, investigator, ethics-committee and monitor responsibilities, defines the Clinical Investigation Plan (CIP), governs adverse-event reporting, and underpins clinical evidence used in EU MDR conformity assessment, FDA IDE submissions and ISO 13485 design-control activities.
01Scope and status
ISO 14155 specifies general requirements intended to protect the rights, safety and well-being of human subjects, ensure scientific conduct of the clinical investigation, and ensure credible clinical investigation results. It applies to pre-market and post-market clinical investigations of any medical device on human subjects. It is harmonised under EU MDR (with Annex Z modifications) and is the standard FDA references in IDE submissions when sponsors cite international GCP.
02Structure of the standard
- Ethical considerations — informed consent, ethics-committee involvement, vulnerable subjects.
- Clinical investigation planning — CIP content, risk assessment, investigator brochure, monitoring plan.
- Conduct — investigator responsibilities, sponsor responsibilities, adverse-event recording, deviations.
- Suspension, termination and close-out.
- Responsibilities — sponsor, monitor, principal investigator, coordinating investigator, ethics committee.
- Annexes covering the CIP template, IB content, case-report-form content, final report, and labelling of investigational devices.
03Sponsor responsibilities
- Risk assessment and benefit-risk justification, anchored in ISO 14971.
- Selection and qualification of investigation sites and investigators.
- Investigator brochure preparation and updates as new safety information emerges.
- Clinical Investigation Plan preparation and any amendments.
- Monitoring plan and execution proportionate to risk (centralised, on-site, hybrid).
- Adverse-event collection, assessment and regulatory reporting per MDR Article 80, MDCG guidance, FDA 21 CFR 812 or applicable jurisdiction.
- Final clinical investigation report — content per Annex D of the standard.
- Archiving — 15 years for implantable devices (10 years for other devices) per EU MDR; jurisdiction-specific elsewhere.
04The Clinical Investigation Plan
The CIP is the controlling document for the investigation. Annex A of ISO 14155 prescribes its content: background and rationale, objectives and hypotheses, risk-benefit analysis, design (controlled, comparator, blinding), population, endpoints (primary and secondary), statistical considerations (sample size, analysis populations, missing-data handling), conduct procedures, adverse-event definitions and reporting, monitoring plan, data management, ethics, publication policy. CIP amendments are formally version-controlled and require ethics-committee re-approval where they affect subjects.
05Investigator responsibilities
- Qualification, training, GCP training current.
- Informed consent process — documented, contemporaneous, signed before any study-specific procedure.
- Conduct per the CIP — deviations recorded and reported to sponsor.
- Adverse-event recording and reporting to sponsor per CIP timelines.
- Source-document maintenance allowing reconstruction of the trial.
- Investigator site file maintained for the regulatory archive period.
06Adverse-event classification
ISO 14155 defines key terms used in MDR Article 80 reporting:
| Term | Definition (paraphrase) |
|---|---|
| Adverse Event (AE) | Any untoward medical occurrence in a subject |
| Adverse Device Effect (ADE) | AE related to the use of an investigational device |
| Serious Adverse Event (SAE) | AE leading to death, serious deterioration, foetal distress, hospitalisation, or chronic disease |
| Serious Adverse Device Effect (SADE) | Serious AE attributable to the investigational device |
| Unanticipated SADE (USADE) | SADE whose nature, severity or outcome was not identified in the current risk analysis |
| Device Deficiency | Inadequacy of a device with respect to identity, quality, durability, reliability, usability, safety or performance |
07Monitoring
Risk-based monitoring (RBM) is explicitly accepted. Sponsors define monitoring scope and intensity proportionate to risk and complexity: centralised statistical monitoring, remote source-data review, on-site source-data verification, or hybrid models. The monitoring plan and rationale go into the CIP or a referenced document. Inspection-readiness depends on monitoring evidence being traceable end-to-end.
08Interaction with EU MDR
- MDR Article 62 categorises clinical investigations and sets the application/notification regime.
- Annex XV specifies the documentation expected — most of which is structured per ISO 14155.
- MDR Article 80 sets the reporting obligations for SAEs, ADEs and device deficiencies.
- MDCG 2021-08 provides the EUDAMED-aligned templates for clinical-investigation documents.
- Post-market clinical follow-up (PMCF) studies fall under PMS but also reference ISO 14155 for conduct.
09Interaction with FDA
- FDA accepts ISO 14155 as a consensus standard.
- Investigational Device Exemptions (IDE) under 21 CFR Part 812 establish the US framework; sponsors can run a single-protocol global study designed to satisfy both 14155 and Part 812.
- Informed-consent content must satisfy 21 CFR Part 50 in US sites; 14155 plus Part 50 forms the baseline.
- IDE annual reports and final reports follow Part 812 structure even when 14155 governs conduct.
10How V5 handles this
Frequently asked questions
Q.Is ISO 14155 mandatory?+
It is not a regulation, but it is the de facto global GCP standard for device investigations. EU MDR effectively requires it (through Annex XV and Annex Z) and FDA recognises it as a consensus standard.
Q.Does ISO 14155 apply to in vitro diagnostics?+
No — IVDs are covered by ISO 20916:2019 (clinical performance studies). The two standards share structure and many concepts but are scoped to their respective device families.
Q.Is post-market clinical follow-up covered?+
PMCF studies that are interventional are within scope. Observational registries follow ISO 14155 principles plus jurisdiction-specific guidance (MDCG, FDA Real-World Evidence).
Q.How does ISO 14155:2020 differ from the 2011 edition?+
The 2020 edition strengthened risk-based monitoring, post-market clinical investigation requirements, ethics-committee expectations, vulnerable-population protections, and harmonisation with ISO 14971 and MDR/IVDR. Sponsors operating to the 2011 edition should update SOPs.
Primary sources
Further reading
V5 Ultimate ships with the ISO 14155:2020 — Clinical investigation of medical devices controls already wired in — audit trail, e-signatures, validation evidence. Free trial, no credit card, onboard in days, not months.