Standard Operating Procedure for Phase Separation Techniques in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/025/2025 |
| Supersedes | SOP/API/025/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To establish a procedure for conducting phase separation efficiently and safely in API manufacturing, including the handling of aqueous-organic and solvent-based separations using decanters, separators, or phase separation tanks.
2. Scope
This SOP applies to all two-phase liquid separation activities carried out in production reactors or dedicated phase separation tanks as part of the synthesis or purification process in API manufacturing.
3. Responsibilities
- Production Operator: Execute phase separation as per the BMR and record relevant parameters.
- Process Engineer: Verify layer densities and interface levels; ensure process efficiency.
- QA Personnel: Review logbooks and monitor compliance to phase separation controls.
4. Accountability
The Production Manager is accountable for the execution of phase separation operations, while the QA Head ensures documentation and compliance.
5. Procedure
5.1 Prerequisites
- Review the BMR for:
- Nature of the phases (aqueous/organic)
- Specific gravity of each layer
- Separation equipment (decanter, phase separator)
- Verify:
- Integrity and cleanliness of the separation vessel
- Calibration status of interface level sensor (if automated)
- Drain valve operation
5.2 Execution of Phase Separation
- Allow the reaction mass or mixture to settle undisturbed for the required time (typically 30–60 minutes unless otherwise specified).
- Use visual level observation, interface meter, or gravity difference to identify layers.
- Open the bottom valve slowly to allow the heavier phase (typically aqueous) to drain into the collection vessel.
- Close the valve as soon as the interface is reached. Collect a sample from each phase for identification (Annexure-1).
- Repeat for top phase collection into a separate container, label appropriately.
- If required, repeat phase separation after washing or re-extraction steps.
5.3 Safety and Environmental Considerations
- Use flameproof motors and grounding in case of flammable solvents.
- Vent vapors to scrubber if volatile components are involved.
- Ensure proper PPE: chemical goggles, gloves, face shield, apron.
- Ensure aqueous waste or organic solvent is sent to ETP or recovery unit respectively.
5.4 Documentation
- Record:
- Start and end time of separation
- Volume/weight of each phase
- Identification results
- Final disposal/reprocessing path
- Use the “Phase Separation Logbook” (Annexure-2).
- Attach phase sample labels and retain for QA reference.
6. Abbreviations
- SOP: Standard Operating Procedure
- BMR: Batch Manufacturing Record
- QA: Quality Assurance
- ETP: Effluent Treatment Plant
7. Documents
- Phase Sample Identification Form (Annexure-1)
- Phase Separation Logbook (Annexure-2)
- Drain Valve Inspection Checklist (Annexure-3)
8. References
- ICH Q7 – GMP for Active Pharmaceutical Ingredients
- 21 CFR Part 211 – cGMP for Finished Pharmaceuticals
- WHO GMP Guidelines – Waste Management in Pharmaceutical Manufacturing
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Phase Sample Identification Form
| Batch No. | Phase Type | Container ID | Appearance | Sampled By | Test Result |
|---|---|---|---|---|---|
| API-202504 | Aqueous | CT-01 | Clear | Confirmed |
Annexure-2: Phase Separation Logbook
| Date | Batch No. | Start Time | End Time | Phase Separated | Volume (L) | Operator |
|---|---|---|---|---|---|---|
| 13/04/2025 | API-202504 | 10:30 | 11:15 | Aqueous | 200 |
Annexure-3: Drain Valve Inspection Checklist
| Valve ID | Date | Inspected By | Status | Remarks |
|---|---|---|---|---|
| DV-05 | 13/04/2025 | Functional | No leaks |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial Version | New SOP Release | QA Head |
| 13/04/2025 | 2.0 | Added Inspection Checklist & Safety Notes | Process Improvement | QA Head |