How to Apply the ICH E Guidelines: Operational Guide for QA/QP
How to Apply the ICH E Guidelines: Operational Guide for QA/QP
Introduction
The ICH E Guidelines define the global requirements to ensure quality in clinical studies. For QA and QP professionals, their value is not only regulatory but highly operational: supervision, documentation management, data integrity and risk-based oversight are essential for GCP compliance.
This step-by-step guide translates the regulatory requirements into concrete, actionable activities.
Step 1: Assess the Sponsor’s QMS
QA and QP must first verify that the Quality Management System is:
- aligned with ICH E6(R3) principles,
- risk-based (QbD + QRM),
- supported by updated SOPs,
- backed by monitoring plans consistent with study complexity.
The sponsor must clearly define roles, delegations and decision-making processes. If not, the risk of a Major finding is high.
Step 2: Verify Delegations and CRO Oversight
Any activity outsourced to a CRO or vendor must be:
- formally defined in contracts,
- properly documented within the TMF,
- supervised through co-monitoring, review reports, KPIs and QTL.
Real case studies demonstrate that lack of oversight evidence leads to immediate critical deviations.
Step 3: Check the Investigator and Delegations
QA/QP must ensure that the site has:
- a qualified investigator (CV, GCP training),
- an updated delegation log proportional to task criticality,
- clear processes for SAE and SUSAR reporting,
- compliant IMP management and complete accountability.
ICH E Guidelines emphasise that no delegation removes the principal investigator’s ultimate responsibility.
Step 4: Ensure an Audit-Ready TMF
Checklist:
- complete, version-controlled and accessible documents
- Essential Records updated in real time
- oversight evidence included
- alignment between sponsor TMF and ISF
- audit trails and electronic records incorporated
An incomplete TMF is one of the most frequently cited findings during EMA/MHRA inspections.
Step 5: Implement Risk-Based Quality Management
The guideline outlines the phases of QRM:
- risk identification
- assessment (probability, impact, detectability)
- mitigation
- monitoring
- periodic review
Useful tools for QA/QP:
- Quality Tolerance Limits (QTL)
- central monitoring
- trigger points for site escalation
Step 6: Manage Data Integrity
Critical controls include:
- planned, risk-based audit trail review
- user and privilege management
- validation of systems (EDC, ePRO, eTMF, IRT)
- checks on data transfers between systems
- protection of the study blind
Common errors:
- shared accounts
- unreviewed audit trails
- unvalidated systems
- late unverified changes to critical data
How to Handle a Non-Conformity
When a deviation emerges:
- document immediately
- perform root cause analysis
- assess impact on patient safety and data integrity
- implement measurable CAPA
- update SOPs or training when necessary
GMP Best Practices for QA/QP
- Maintain an inspection mindset: TMF always ready
- Synchronise protocol amendments with electronic systems
- Regularly review RSI and safety processes
- Ensure relevant audit trails are stored in the TMF
- Request targeted training on QRM and data governance
Real Scenario
A sponsor receives a Major finding: incomplete TMF and undocumented CRO oversight.
QA/QP intervention:
- reconstruction of missing documentation
- implementation of quality KPIs
- review of contracts and delegation definitions
- update of the Monitoring Plan
Result: the study returns to compliance within three months.
Conclusion
The ICH E Guidelines become powerful operational tools when applied correctly. Through a structured, risk-based approach, QA and QP can ensure clinical studies that are robust, safe and fully audit-ready.
Discover the full guide on GuideGxP.com.