API Manufacturing: SOP for Phase Separation Techniques – V 2.0

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