Standard Operating Procedure for Distillation and Purification of Recovered Solvents in API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/042/2025
Supersedes	SOP/API/042/2022
Page No.	Page 1 of 10
Issue Date	13/04/2025
Effective Date	15/04/2025
Review Date	13/04/2026

1. Purpose

To define a validated procedure for the distillation and purification of recovered solvents to ensure their suitability for reuse in API manufacturing, thereby reducing waste and complying with GMP and environmental regulations.

2. Scope

This SOP applies to the distillation and purification operations for solvents recovered from production areas in the API manufacturing facility using in-house recovery systems.

3. Responsibilities

• Production Operator: Perform distillation activities and monitor process parameters.
• Engineering Department: Maintain distillation unit and ensure utility availability.
• QA Department: Verify documentation and approve purified solvent for reuse.
• QC Department: Analyze recovered solvent samples for quality testing.

4. Accountability

The Production Manager is accountable for implementation of the distillation process. QA Manager is responsible for ensuring compliance and authorizing the reuse of recovered solvents.

5. Procedure

5.1 Equipment and Setup

1. Ensure availability of clean and calibrated distillation equipment including:
   • Distillation vessel
   • Condenser
   • Receiver tank
   • Thermocouple and pressure gauge
2. Check utilities: heating system, chilled water circulation, and vacuum pump.
3. Verify previous product residue has been removed (refer cleaning SOP).

5.2 Loading and Process Initiation

1. Transfer used solvent from labeled drums to the distillation vessel using closed pipelines.
2. Ensure solvent identity and quantity are recorded in the “Solvent Recovery Log” (Annexure-1).
3. Start heating slowly while monitoring temperature and pressure.
4. Collect solvent fractions as per boiling range data under atmospheric or vacuum conditions.
5. Condensed purified solvent should be collected in pre-cleaned labeled containers.

5.3 Process Monitoring and Control

1. Monitor and record:
   • Distillation start time
   • Jacket temperature
   • Reflux ratio
   • Vacuum level
2. Ensure no over-boiling or contamination of the receiver.
3. Stop distillation once residue volume or temperature exceeds control limits.

5.4 Quality Testing and Release

1. Collect purified solvent samples and send to QC for testing:
   • Purity
   • Boiling point
   • Color and odor
   • Non-volatile residue
2. Compare with respective solvent specifications.
3. Label as “Purified Solvent – Approved for Reuse” or “Rejected” based on QC report (Annexure-2).

5.5 Documentation and Storage

1. Enter all recovery data in the “Purified Solvent Inventory Register” (Annexure-3).
2. Store approved solvents in designated solvent tanks or drums with status labels.
3. Rejected solvents must be disposed of as per hazardous waste disposal SOP.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• QC: Quality Control
• API: Active Pharmaceutical Ingredient
• ppm: Parts per million

7. Documents

1. Solvent Recovery Log (Annexure-1)
2. Purified Solvent QC Report (Annexure-2)
3. Purified Solvent Inventory Register (Annexure-3)

8. References

• ICH Q7 – Good Manufacturing Practice Guide for APIs
• 21 CFR Part 211 – Subpart D & E
• WHO TRS 986 – Annex on Recovered Solvents

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Solvent Recovery Log

Date	Solvent Name	Batch No.	Recovered Qty (L)	Start Time	End Time
13/04/2025	Ethyl Acetate	API-202506	120	08:00	11:30

Annexure-2: Purified Solvent QC Report

Sample ID	Test	Result	Specification	Status
QC-SOL-025	Purity	99.8%	≥99.5%	Pass

Annexure-3: Purified Solvent Inventory Register

Date	Solvent	Qty Approved (L)	Storage Tank/Drum ID	Label Status
13/04/2025	Ethyl Acetate	120	ST-11	Approved for Reuse

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP Release	New Equipment Installation	QA Head
13/04/2025	2.0	Added Annexures and QC Release Controls	Regulatory Compliance	QA Head