ICH E6(R3), the rewrite of Good Clinical Practice adopted in January 2025 and now in effect in the EU and other ICH regions, is less a list of new rules than a change of posture. The guideline asks sponsors and investigators to identify what matters to participant safety and to the reliability of results, and to put effort there, rather than treating every data point and every document as equally critical.
Quality by design, not quality by inspection
The principles section leads with risk proportionality. Protocols, monitoring plans and data management plans are expected to show how critical-to-quality factors were identified and how the study design controls them. On a practical level, that means the risk assessment is no longer an appendix that gets written after the protocol is final; it shapes the protocol.
What changes for monitoring
E6(R3) explicitly supports centralised and remote monitoring alongside on-site visits, and expects the mix to follow the risk profile. Sponsors who still run 100% source data verification on low-risk fields will find it hard to justify. Monitoring plans should state which data and processes are critical, what the key risk indicators are, and what triggers a change in monitoring intensity.
Investigator oversight and delegation
The guideline is clearer about the investigator's accountability for tasks delegated to site staff and to service providers, including decentralised-trial vendors. Delegation logs, training evidence and oversight records will be looked at more closely, which affects how sites are qualified and how CRAs document site visits.
Data governance
A new emphasis on data integrity across the whole data flow: computerised systems, metadata, audit trails and the ability to reconstruct what happened. Sponsors should be able to show the data lifecycle for critical data, from capture through to the analysis dataset.
What to do now
- Re-read your monitoring plan template. If it does not reference critical-to-quality factors and key risk indicators, it is out of date.
- Check that your risk assessment is produced before protocol finalisation and revisited at defined points.
- Update CRA training so visit reports capture oversight and delegation evidence, not only SDV counts.
- Map the data flow for critical data on an active study and confirm audit trails are reviewable.
Vakula Tech supports sponsors and CROs with trial monitoring, trial management and GxP audit. If you want a second pair of eyes on a monitoring plan before an inspection, contact us.