Standard Operating Procedure for Re-Dosing in Cross-Over Study Designs in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/070/2025 |
| Supersedes | SOP/BA-BE/070/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define a clear and compliant procedure for the re-dosing of participants in cross-over Bioavailability/Bioequivalence (BA/BE) studies, ensuring protocol adherence, subject safety, and regulatory conformity.
2. Scope
This SOP applies to all re-dosing events in cross-over study designs, typically conducted in Period 2 or Period 3 of BA/BE studies, following the washout period. It covers eligibility assessment, safety confirmation, re-dosing administration, and documentation.
3. Responsibilities
- Principal Investigator (PI): Approves re-dosing eligibility, oversees dosing, and signs off on re-dosing documentation.
- Clinical Research Coordinator (CRC): Coordinates scheduling, ensures pre-dosing requirements are met, and updates records.
- Nursing Staff: Performs pre-dosing checks, supervises dosing, and reports any abnormalities.
4. Accountability
The Principal Investigator is accountable for ensuring that re-dosing is performed only after confirming protocol compliance, washout completion, subject health status, and documentation readiness.
5. Procedure
5.1 Confirmation of Washout Period
- Verify that the washout period defined in the protocol (e.g., 7 days or 5 half-lives) has been completed.
- Document washout start and end dates in Annexure-1: Re-Dosing Eligibility Checklist.
5.2 Pre-Re-Dosing Assessment
- Conduct:
- Vital signs check
- Physical examination
- Laboratory safety tests (if required)
- ECG and AE review from previous period
- Only subjects with satisfactory medical clearance proceed to re-dosing.
5.3 Subject Consent Confirmation
- Reconfirm willingness and eligibility for continued participation.
- Ensure that any new risks or AEs are communicated and documented.
5.4 Re-Dosing Procedure
- Follow the same dosing process as Period 1:
- Administer correct formulation (Test or Reference) as per randomization schedule
- Confirm water volume, fasting/fed status, and supervision
- Document all entries in Annexure-2: Re-Dosing Record Sheet
5.5 Post-Dose Monitoring
- Monitor for AEs, vitals, and protocol-specific parameters.
- Record all observations in subject CRFs and Annexure-3: Post Re-Dose Safety Monitoring Log.
5.6 Deviation Handling
- Any delay or failure to re-dose as per scheduled window must be documented in Annexure-4: Re-Dosing Deviation Log and escalated to the PI.
6. Abbreviations
- BA: Bioavailability
- BE: Bioequivalence
- CRF: Case Report Form
- PI: Principal Investigator
- AE: Adverse Event
7. Documents
- Re-Dosing Eligibility Checklist – Annexure-1
- Re-Dosing Record Sheet – Annexure-2
- Post Re-Dose Safety Monitoring Log – Annexure-3
- Re-Dosing Deviation Log – Annexure-4
8. References
- ICH E6(R2) – Good Clinical Practice
- CDSCO Guidelines on BA/BE Studies
- Study-Specific Protocol
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Re-Dosing Eligibility Checklist
| Subject ID | Washout Period (Days) | Vitals Normal | Lab Clearance | Investigator Approval |
|---|---|---|---|---|
| VOL-070 | 8 | Yes | Yes | Approved |
Annexure-2: Re-Dosing Record Sheet
| Subject ID | Date | Formulation | Dose Time | Fasted/Fed | Water Volume | Dosed By |
|---|---|---|---|---|---|---|
| VOL-070 | 17/04/2025 | Reference | 07:05 | Fasted | 240 mL | Dr. Sunita Reddy |
Annexure-3: Post Re-Dose Safety Monitoring Log
| Subject ID | Timepoints | Vitals | AEs Noted | Initials |
|---|---|---|---|---|
| VOL-070 | 0.5h, 1h, 2h | Normal | None | R. Pawar |
Annexure-4: Re-Dosing Deviation Log
| Subject ID | Deviation Description | Time | Action Taken | Investigator Review |
|---|---|---|---|---|
| VOL-070X | Dosed 15 min late | 07:20 | Included, deviation documented | Dr. Arvind Shah |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 12/01/2022 | 1.0 | Initial release | Study requirement | QA Head |
| 17/04/2025 | 2.0 | Added deviation handling and annexures | Audit recommendation | QA Head |