Standard Operating Procedure for Crossover Period Washout Management in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/083/2025 |
| Supersedes | SOP/BA-BE/083/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the process for managing the washout period between two periods of a crossover design in Bioavailability/Bioequivalence (BA/BE) studies, ensuring subject compliance, safety, and data integrity.
2. Scope
This SOP applies to clinical and volunteer management staff involved in monitoring and managing healthy volunteers during the washout phase of crossover studies at the clinical research facility.
3. Responsibilities
- Clinical Research Coordinator (CRC): Monitors subject health and ensures adherence to study instructions during the washout.
- Volunteer Coordinator: Maintains contact with subjects and tracks availability for the next study period.
- Principal Investigator (PI): Ensures proper medical oversight and reviews any events occurring during the washout period.
4. Accountability
The Study Director is accountable for ensuring protocol-defined washout durations are adhered to, with proper documentation and subject compliance maintained throughout the washout phase.
5. Procedure
5.1 Washout Duration
- Determine the washout period as per the approved clinical protocol and based on the elimination half-life (t1/2) of the drug.
- The standard washout period should be at least 5 times the t1/2 of the study drug to avoid carryover effects.
5.2 Volunteer Discharge and Instructions
- At the end of the first study period, discharge volunteers only after:
- Vital signs are stable
- All post-dose safety assessments are completed
- Provide verbal and written washout instructions (Annexure-1: Washout Instruction Form), including:
- Dietary restrictions
- Avoidance of alcohol, tobacco, and medication
- Contact number for any medical emergency
5.3 Remote Monitoring of Subjects
- CRC or designated staff should maintain regular contact with subjects to:
- Confirm adherence to restrictions
- Track any symptoms or adverse events
- Confirm availability for next check-in
- Document each interaction in Annexure-2: Washout Monitoring Log.
5.4 Re-admission for Next Period
- On re-admission, verify:
- Identity of the subject
- Adherence to restrictions (e.g., through self-declaration form)
- Conduct physical exam, vital signs check, and pregnancy test (if applicable) before next period dosing.
- Document in Annexure-3: Washout Compliance Assessment Form.
5.5 Deviations During Washout
- Document any protocol deviations, non-compliance, or adverse events in Annexure-4: Washout Deviation Log.
- Evaluate impact on study outcomes and decide whether to continue, replace, or exclude the subject from subsequent periods.
6. Abbreviations
- BA: Bioavailability
- BE: Bioequivalence
- CRC: Clinical Research Coordinator
- PI: Principal Investigator
- t1/2: Elimination Half-Life
7. Documents
- Washout Instruction Form – Annexure-1
- Washout Monitoring Log – Annexure-2
- Washout Compliance Assessment Form – Annexure-3
- Washout Deviation Log – Annexure-4
8. References
- ICH E6(R2) – Good Clinical Practice
- US FDA Guidance for Industry – BA/BE Studies
- Clinical Study 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: Washout Instruction Form
| Subject ID | Period Completed | Instructions Given | Given By | Signature |
|---|---|---|---|---|
| VOL-083 | Period 1 | Avoid alcohol, OTC meds | Sunita Reddy | Subject Signed |
Annexure-2: Washout Monitoring Log
| Date | Subject ID | Mode of Contact | Feedback | Contacted By |
|---|---|---|---|---|
| 15/04/2025 | VOL-083 | Phone | No issues reported | Ravi Nair |
Annexure-3: Washout Compliance Assessment Form
| Subject ID | Declaration Signed | Vital Signs Normal | Examined By | Eligible for Next Period |
|---|---|---|---|---|
| VOL-083 | Yes | Yes | Dr. Arvind Shah | Yes |
Annexure-4: Washout Deviation Log
| Date | Subject ID | Deviation Description | Impact Assessment | Action Taken |
|---|---|---|---|---|
| 16/04/2025 | VOL-083 | Consumed paracetamol | Reported to PI | Excluded from P2 |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 10/01/2022 | 1.0 | Initial SOP | GCP Requirement | QA Head |
| 17/04/2025 | 2.0 | Added annexures and deviation tracking | Audit Preparedness | QA Head |