ICH E Guidelines: Essential Guide for QA and QP

Introduction

The ICH E Guidelines form the regulatory backbone of modern clinical research. For QA and QP professionals, understanding their practical application is crucial: clinical studies are the core of the regulatory dossier, and the data generated become the basis for assessing the safety and efficacy of a medicinal product.
With the revision ICH E6(R3), Good Clinical Practice evolves toward a quality-by-design approach, a robust risk-based management system, and strengthened data integrity — all essential elements in any EMA/FDA inspection.

Discover the principles of the ICH E Guidelines for clinical studies and GCP: responsibilities, risks, documentation, and data quality — explained specifically for QA/QP.

The Efficacy Guidelines ICH E – Clinical Studies, GCP, E6(R3) provide a comprehensive overview of GCP governance, the responsibilities of sponsors, CROs and investigators, the pharmacovigilance principles under ICH E2, and the correct management of the Trial Master File (TMF).
This article introduces the fundamental concepts to give QA/QP a clear understanding of real risks and inspector expectations.

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Regulatory Focus: ICH E6(R3) and Quality by Design

The revision of ICH E6(R3) marks a true paradigm shift. It is no longer sufficient to review quality retrospectively — quality must be built into the study design. The guideline defines:

• ethical and scientific criteria for clinical trials
• responsibilities of sponsor, CRO and investigator
• proportional, risk-based quality management
• data governance and electronic system requirements
• essential documentation and TMF management
• integration with pharmacovigilance principles (ICH E2)

Confirmed in 2025 and entering EMA implementation on 31 July 2025, it will become the new global standard.

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Responsibilities of Sponsor and CRO

The ICH E Guidelines clarify that a sponsor may delegate activities to CROs or service providers — but cannot delegate ultimate responsibility for the trial.

Key obligations include:

• establishing a study-appropriate Quality Management System
• ensuring documented oversight of delegated activities
• implementing risk-based monitoring
• maintaining a complete, current, and audit-ready TMF

Real-world cases reported in the guideline highlight critical findings related to non-formalised delegations, insufficient oversight and incomplete TMF documentation.

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Investigator: Essential Controls for QA/QP

The investigator is responsible for conducting the study at the trial site and must:

• be qualified and adequately trained
• maintain an updated delegation log proportional to task criticality
• ensure proper management of the Investigational Medicinal Product (IMP)
• document all critical data in a timely manner
• retain Essential Records for at least 25 years (EU requirement)

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TMF and Essential Records: Why Inspectors Start Here

For QA/QP, the TMF is one of the most critical inspection areas. The guideline reiterates:

• “If it isn’t documented, it didn’t happen”
• documents must be complete, version-controlled and available in real time
• documentation must include not only formal records but also oversight evidence
• electronic data, audit trails and validated systems are part of the Essential Records

A TMF misaligned between sponsor and site has resulted in multiple Major findings during inspections.

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Data Integrity in the ICH E Guidelines

The Data Governance section of E6(R3) reinforces ALCOA+ principles and introduces new expectations:

• risk-based audit trail review
• protection of the blind in double-blind studies
• controls over data transfers between systems
• validation of protocol configurations within electronic systems
• robust user management and cybersecurity measures

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Pharmacovigilance: The Role of ICH E2

The ICH E2 documents define:

• AE, SAE and SUSAR definitions and reporting requirements (E2A)
• structure of ICSRs and E2B(R3) format
• periodic benefit–risk evaluation (E2C(R2))
• post-approval safety management (E2D)

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Career Impact for QA/QP

In-depth knowledge of the ICH E Guidelines is now a core requirement for senior roles in QA and Qualified Person functions. It is essential for:

• reviewing TMFs and GCP processes
• supporting audits and international inspections
• assessing risks, electronic systems and data integrity
• interacting authoritatively with sponsors, CROs and investigators

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FAQ

1. Are the ICH E Guidelines mandatory?
Yes. EMA, FDA and MHRA adopt them as global references for evaluating clinical studies.

2. What truly changes with E6(R3)?
Risk-based quality management, stronger focus on data integrity, digital governance and clearer delegation responsibilities.

3. What are the most common findings in clinical trials?
Insufficient oversight of CROs, outdated TMF, unreviewed audit trails, non-formalised delegations.

4. Who needs to understand the ICH E Guidelines?
QA, QP, Clinical Operations, Regulatory, Pharmacovigilance and Sponsors.

5. What is the most important document according to inspectors?
The TMF — it is the first item requested in any GCP inspection.

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Conclusion

The ICH E Guidelines form the essential framework for ensuring clinical studies are ethical, safe and reliable. For QA and QP professionals, they are an indispensable reference to guarantee quality, data integrity and regulatory compliance. Discover the full guide on GuideGxP.com.