Standard Operating Procedure for Handling of Mixed Solvent Streams in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/053/2025 |
| Supersedes | SOP/API/053/2022 |
| 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 standard procedure for the safe handling, segregation, and disposal or recovery of mixed solvent streams generated during API manufacturing to avoid cross-contamination, ensure regulatory compliance, and minimize environmental risk.
2. Scope
This SOP applies to all departments and operations within API manufacturing where more than one solvent is collected together during processing, cleaning, or waste management activities.
3. Responsibilities
- Production Team: Identify and label all mixed solvent containers; follow disposal/recovery instructions.
- Engineering Team: Maintain collection systems and containers.
- EHS Team: Ensure proper segregation and authorized disposal methods.
- QA Department: Review documentation and ensure compliance with internal and external standards.
4. Accountability
The EHS Head is accountable for the safe and compliant management of mixed solvent streams. The Production Head ensures adherence to segregation and labeling procedures.
5. Procedure
5.1 Identification of Mixed Solvent Streams
- Recognize solvent mixtures generated during:
- Solvent washes
- Line flushing
- Batch changeover cleaning
- Multi-solvent reaction residue collection
- Note physical properties (color, odor, phase separation) and source in the “Mixed Solvent Register” (Annexure-1).
5.2 Segregation and Labeling
- Transfer mixed solvents to HDPE or stainless-steel drums with secure lids.
- Each container must be labeled with:
- “Mixed Solvent Stream – Not for Direct Reuse”
- Collection date
- Approximate composition (if known)
- Operator initials
- Use color-coded labels (e.g., orange for mixed waste solvents).
5.3 Storage and Temporary Holding
- Store mixed solvent drums in a designated area with:
- Secondary containment
- Proper ventilation
- Firefighting equipment
- Maintain daily checks for drum integrity, leaks, or venting issues.
5.4 Processing or Disposal
- Depending on composition, route streams to:
- In-house distillation (if possible)
- Third-party disposal (CPCB-approved)
- Incineration (if hazardous)
- Document the fate of each drum in the “Solvent Disposal/Recovery Log” (Annexure-2).
5.5 Documentation and Records
- Ensure real-time entry of collected volumes, disposal route, and handling personnel.
- QA must review logs monthly and sign off.
- All records to be retained for a minimum of 5 years.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- EHS: Environment, Health & Safety
- CPCB: Central Pollution Control Board
7. Documents
- Mixed Solvent Register (Annexure-1)
- Solvent Disposal/Recovery Log (Annexure-2)
8. References
- ICH Q7 – GMP for Active Pharmaceutical Ingredients
- CPCB Guidelines for Hazardous Waste
- 21 CFR Part 211 – Subpart D
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Mixed Solvent Register
| Date | Stream ID | Source | Approx. Composition | Volume (L) | Operator |
|---|---|---|---|---|---|
| 13/04/2025 | MS-001 | Reactor Wash | Toluene + Acetone | 45 |
Annexure-2: Solvent Disposal/Recovery Log
| Stream ID | Volume (L) | Route | Vendor (if applicable) | Date | Handled By |
|---|---|---|---|---|---|
| MS-001 | 45 | Third-Party Disposal | GreenWaste Ltd. | 14/04/2025 |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP | GMP Compliance | QA Head |
| 13/04/2025 | 2.0 | Updated with color coding and Annexures | Internal Audit Observation | QA Head |