Standard Operating Procedure for Blinding and Unblinding Protocols in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/028/2025 |
| Supersedes | SOP/BA-BE/028/2022 |
| Page No. | Page 1 of 13 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the standard procedure for the blinding and unblinding of treatment assignments in Bioavailability/Bioequivalence (BA/BE) studies, in order to maintain the integrity of the study and ensure unbiased assessment of results.
2. Scope
This SOP applies to all blinded or partially blinded BA/BE studies conducted under the sponsorship or management of the organization. It includes single-blind, double-blind, and investigator-blind study designs.
3. Responsibilities
- Clinical Operations: Oversees execution of blinding processes at the site.
- Randomization Coordinator: Generates randomization codes and maintains the code list securely.
- Principal Investigator: Ensures that blinding is maintained and reports any inadvertent unblinding.
- Data Management: Handles unblinded data separately and securely when applicable.
4. Accountability
The Head of Clinical Research is accountable for ensuring that blinding is maintained according to the protocol and that any unblinding is adequately documented and justified.
5. Procedure
5.1 Study Design and Blinding Approach
- Refer to the approved protocol to determine the blinding type: single-blind, double-blind, or open-label.
- If applicable, define the blinding mechanism in the protocol and Annexure-1: Blinding Plan Summary.
5.2 Randomization and Blinding Code Preparation
- Generate randomization codes using validated software and maintain a sealed master list (Annexure-2).
- Label study drugs identically for active and reference treatments, as required.
- Maintain strict access control to randomization lists and drug code identifiers.
5.3 Implementation of Blinding at Site
- Provide site personnel with blinded kits without revealing identity or sequence.
- Ensure pharmacy or designated person dispenses according to randomization schedule.
- Record dispensation and administration details in Annexure-3: Blinding Compliance Log.
5.4 Monitoring and Maintenance of Blind
- Monitor blinding compliance during site visits and audits.
- Investigate any suspected or accidental unblinding events and document in Annexure-4: Unblinding Incident Report.
5.5 Emergency Unblinding
- Unblinding may only occur if knowledge of treatment is essential for subject safety.
- Document:
- Reason for unblinding
- Authorization obtained
- Time and person unblinded
- Update Annexure-5: Emergency Unblinding Log and notify the sponsor and Ethics Committee immediately.
5.6 End-of-Study Unblinding
- Perform unblinding only after database lock and analysis plan finalization.
- Document and archive final unblinding summary (Annexure-6: Study Unblinding Summary Report).
6. Abbreviations
- BA: Bioavailability
- BE: Bioequivalence
- SOP: Standard Operating Procedure
- CRF: Case Report Form
7. Documents
- Blinding Plan Summary – Annexure-1
- Randomization Code List – Annexure-2
- Blinding Compliance Log – Annexure-3
- Unblinding Incident Report – Annexure-4
- Emergency Unblinding Log – Annexure-5
- Study Unblinding Summary Report – Annexure-6
8. References
- ICH E6(R2) – Good Clinical Practice
- Schedule Y – Drugs and Cosmetics Rules
- USFDA Guidance on BE Studies
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Blinding Plan Summary
| Study Code | Blinding Type | Blinded Parties | Remarks |
|---|---|---|---|
| BE-037 | Double-Blind | Subject, Investigator | Parallel design |
Annexure-2: Randomization Code List
| Subject ID | Treatment Sequence | Code |
|---|---|---|
| 001 | TR | A102 |
Annexure-3: Blinding Compliance Log
| Date | Subject ID | Dispensed By | Verified By | Remarks |
|---|---|---|---|---|
| 16/04/2025 | 001 | Technician A | PI | As per randomization |
Annexure-4: Unblinding Incident Report
| Date | Subject ID | Reason | Impact | Action Taken |
|---|---|---|---|---|
| 17/04/2025 | 004 | Label mix-up | Excluded from PK | Reported to QA |
Annexure-5: Emergency Unblinding Log
| Subject ID | Unblinded By | Date & Time | Reason | Authorization |
|---|---|---|---|---|
| 008 | PI | 17/04/2025, 11:45 | Severe reaction | Medical Monitor |
Annexure-6: Study Unblinding Summary Report
| Study Code | Total Subjects | Unblinded Cases | Remarks |
|---|---|---|---|
| BE-037 | 60 | 1 | Emergency unblinding only |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 15/01/2022 | 1.0 | Initial version | Regulatory compliance | QA Head |
| 17/04/2025 | 2.0 | Included emergency and end-of-study unblinding procedures | ICH E6(R2) Alignment | QA Head |