Standard Operating Procedure for Compliance with ICH E6(R2) GCP Addendum in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/045/2025 |
| Supersedes | SOP/BA-BE/045/2022 |
| Page No. | Page 1 of 12 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the process for implementing and ensuring compliance with the ICH E6(R2) Good Clinical Practice (GCP) Addendum requirements in Bioavailability and Bioequivalence (BA/BE) studies, with specific focus on quality management, sponsor oversight, and risk-based monitoring.
2. Scope
This SOP applies to all BA/BE studies sponsored or conducted by the organization, and includes regulatory submissions, CRO oversight, vendor qualification, clinical site operations, and data integrity practices as mandated under ICH E6(R2).
3. Responsibilities
- Quality Assurance (QA): Ensures organization-wide implementation of ICH E6(R2) elements through SOPs and training.
- Clinical Project Manager: Ensures study-specific application of quality risk management and oversight practices.
- Regulatory Affairs: Verifies compliance with E6(R2) requirements in submissions.
- IT/Data Management: Maintains data integrity, validation, and audit trail for electronic systems.
4. Accountability
The Head of Clinical Operations and the Head of QA are jointly accountable for ensuring compliance with ICH E6(R2) principles across all ongoing and future BA/BE trials.
5. Procedure
5.1 Sponsor Oversight
- Ensure written oversight plans are in place for each contracted CRO and vendor using Annexure-1: CRO Oversight Checklist.
- Conduct quarterly governance meetings and maintain minutes in the TMF.
5.2 Quality Management System (QMS)
- Develop and maintain a Quality Management Plan (QMP) for each study.
- Implement procedures to identify, document, and address quality issues, including deviations and CAPAs.
5.3 Risk-Based Monitoring (RBM)
- Perform risk assessment prior to study initiation using Annexure-2: Risk Assessment Template.
- Classify risks as critical, major, or minor, and develop mitigation plans accordingly.
- Define centralized, remote, and on-site monitoring strategies.
5.4 Data Integrity and Documentation
- Ensure source data meets ALCOA+ principles: Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, and Available.
- Use validated electronic systems that generate audit trails and control user access.
5.5 Training and Compliance
- All study personnel must be trained on ICH E6(R2) requirements using Annexure-3: Training Attendance Log.
- Refresher training must be conducted annually or when SOPs are revised.
5.6 Continuous Improvement
- Lessons learned and audit findings must be recorded and reviewed quarterly.
- Update risk plans and QMPs as needed and document changes in Annexure-4: Quality Issue Log.
6. Abbreviations
- BA: Bioavailability
- BE: Bioequivalence
- RBM: Risk-Based Monitoring
- QMS: Quality Management System
- ALCOA+: Data Integrity Principles
- CRO: Contract Research Organization
7. Documents
- CRO Oversight Checklist – Annexure-1
- Risk Assessment Template – Annexure-2
- Training Attendance Log – Annexure-3
- Quality Issue Log – Annexure-4
8. References
- ICH E6(R2) – Guideline for Good Clinical Practice
- EMA Reflection Paper on Risk-Based Quality Management
- 21 CFR Part 11 – Electronic Records and Signatures
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: CRO Oversight Checklist
| Item | Status (Yes/No) | Comments |
|---|---|---|
| Governance Meetings Conducted | Yes | Held monthly since study start |
Annexure-2: Risk Assessment Template
| Risk | Impact | Probability | Score | Mitigation |
|---|---|---|---|---|
| Volunteer Dropout | High | Medium | 6 | Maintain backup pool |
Annexure-3: Training Attendance Log
| Name | Designation | Training Date | Trainer | Signature |
|---|---|---|---|---|
| Sunita Reddy | Study Coordinator | 05/04/2025 | Dr. Arvind Shah |
Annexure-4: Quality Issue Log
| Issue ID | Description | Date Identified | Corrective Action | Status |
|---|---|---|---|---|
| QI-01 | Missing audit trail for two source files | 11/04/2025 | Enabled file-level audit logging | Closed |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 10/01/2022 | 1.0 | Initial SOP | GCP compliance framework | QA Head |
| 17/04/2025 | 2.0 | Aligned with E6(R2) risk-based approach and quality oversight | ICH revision implementation | QA Head |