Standard Operating Procedure for Volume Reconciliation During Elixir Manufacturing
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/199/2025 |
| Supersedes | SOP/ELX/199/2022 |
| Page No. | Page 1 of 8 |
| Issue Date | 11/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 11/04/2026 |
1. Purpose
To establish a standardized procedure for performing volume reconciliation of elixir formulations at key stages during the manufacturing process to ensure accurate yield calculation, regulatory compliance, and to identify and address any volume discrepancies.
2. Scope
This SOP applies to all stages of elixir batch manufacturing where volume measurement is required — including post-addition of major components, after final blending, post-filtration, and before transfer for filling.
3. Responsibilities
- Production Operator:
- Measure and document volume at each defined stage.
- Notify the supervisor and QA in case of any abnormal deviation.
- Production Supervisor:
- Verify measured volumes and calculate expected vs actual reconciliation.
- QA Officer:
- Review volume reconciliation records and investigate deviations if necessary.
4. Accountability
The Production Head is accountable for the correctness of volume measurements. QA is accountable for ensuring reconciliation is within acceptable limits and for addressing any discrepancies.
5.
Procedure
5.1 Stage-Wise Reconciliation Points
- Volume shall be measured and recorded at the following stages:
- After addition of purified water and initial dissolution
- After addition of all active and excipients (pre-final adjustment)
- After final volume adjustment (before sampling)
- After bulk transfer to storage or filling tanks
5.2 Method of Volume Measurement
- Use calibrated tank-level gauges, dipsticks, flow meters, or sight glass as applicable.
- Ensure tank is placed on a level surface and mixing is stopped before measurement.
- Refer to calibration chart/scale for accurate volume reading.
5.3 Yield Calculation
- Calculate theoretical volume from BMR based on ingredient quantities.
- Calculate actual measured volume.
- Use the following formula to calculate yield:
Yield (%) = (Actual Volume / Theoretical Volume) × 100 - Acceptable variation: ±2% unless otherwise justified.
5.4 Action in Case of Deviation
- Inform QA and investigate for possible causes:
- Spillage or evaporation
- Incorrect ingredient quantity or measurement errors
- Tank dead volume or leakage
- Document deviation and initiate corrective action if deviation exceeds limits.
5.5 Documentation
- Enter volume measurements and yield calculations in the Volume Reconciliation Logbook (Annexure-1).
- Attach a copy to the BMR with supervisor and QA signatures.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
- cGMP: Current Good Manufacturing Practices
7. Documents
- Volume Reconciliation Logbook (Annexure-1)
- Batch Manufacturing Record (BMR)
- Tank Calibration Chart
8. References
- 21 CFR Part 211.103 – Calculation of Yield
- WHO TRS 986 – GMP for Pharmaceuticals
- ICH Q8 – Pharmaceutical Development
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Volume Reconciliation Logbook
| Date | Batch No. | Stage | Theoretical Volume (L) | Actual Volume (L) | Yield (%) | Remarks | Verified By (QA) |
|---|---|---|---|---|---|---|---|
| 11/04/2025 | ELX-0425-018 | Final Blend | 1000 | 980 | 98% | Within Limits | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Release | New SOP | QA Head |
| 11/04/2025 | 2.0 | Expanded yield tolerance limits and added dead volume clause | Operational Improvement | QA Head |