ICHRegulatory IntelligenceGuidanceHIGH INSPECTION RISK
ICH E6(R3)

Good Clinical Practice (GCP)

The international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials involving human subjects. E6(R3) restructures GCP around a set of overarching Principles plus Annex 1 (interventional trials), replacing the prescriptive E6(R2) checklist model with a risk-proportionate, quality-by-design approach that is media-agnostic across paper and electronic systems.

LAST REVISED
January 2025
PRODUCT AREAS
Clinical
SCOPE & APPLICABILITY

All interventional clinical trials of investigational products conducted to generate data submitted to regulatory authorities in ICH regions. Annex 1 applies to interventional trials; Annex 2 extends the principles to non-traditional and pragmatic designs.

KEY REQUIREMENTS
  • 01Trials designed around pre-identified factors critical to quality, with proportionate controls
  • 02Informed consent obtained and documented before any trial-specific procedure
  • 03Sponsor oversight of all delegated activities, including vendors and decentralised elements
  • 04ALCOA+ data governance maintained across the entire data lifecycle regardless of medium
  • 05Validated computerised systems with audit trails for electronic trial records
  • 06Safety information reported to sponsors, IRB/IECs, and authorities within required timelines
IMPLEMENTATION TIPS
Rebuild monitoring plans around risk-based monitoring and critical-to-quality factors rather than blanket SDV
Map every data flow (EDC, ePRO, wearables, labs) to an owner and an audit-trail review cadence
Update vendor qualification and oversight SOPs — Annex 1 makes sponsors accountable for delegated tasks
Confirm consent processes cover electronic and remote consent where used
REVISION NOTES

Adopted at Step 4 on 6 January 2025, superseding E6(R2) (2016). Restructured into Principles + Annex 1, explicitly media-agnostic, with strengthened data governance and quality-by-design expectations. Annex 2 for non-traditional designs is expected to finalise later in 2025.

ICH E6(R3): frequently asked questions

Quick answers to common questions about ICH E6(R3).

What is ICH E6(R3)?

ICH E6(R3) — Good Clinical Practice (GCP) — is a guidance issued by the International Council for Harmonisation. The international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials involving human subjects. E6(R3) restructures GCP around a set of overarching Principles plus Annex 1 (interventional trials), replacing the prescriptive E6(R2) checklist model with a risk-proportionate, quality-by-design approach that is media-agnostic across paper and electronic systems.

Who does ICH E6(R3) apply to?

All interventional clinical trials of investigational products conducted to generate data submitted to regulatory authorities in ICH regions. Annex 1 applies to interventional trials; Annex 2 extends the principles to non-traditional and pragmatic designs.

What are the key requirements of ICH E6(R3)?

ICH E6(R3) requires, among other things: Trials designed around pre-identified factors critical to quality, with proportionate controls; Informed consent obtained and documented before any trial-specific procedure; Sponsor oversight of all delegated activities, including vendors and decentralised elements; ALCOA+ data governance maintained across the entire data lifecycle regardless of medium.

When was ICH E6(R3) last updated?

The current version of ICH E6(R3) dates from January 2025. Adopted at Step 4 on 6 January 2025, superseding E6(R2) (2016). Restructured into Principles + Annex 1, explicitly media-agnostic, with strengthened data governance and quality-by-design expectations. Annex 2 for non-traditional designs is expected to finalise later in 2025.

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