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

1. Recognize solvent mixtures generated during:
   • Solvent washes
   • Line flushing
   • Batch changeover cleaning
   • Multi-solvent reaction residue collection
2. Note physical properties (color, odor, phase separation) and source in the “Mixed Solvent Register” (Annexure-1).

5.2 Segregation and Labeling

1. Transfer mixed solvents to HDPE or stainless-steel drums with secure lids.
2. Each container must be labeled with:
   • “Mixed Solvent Stream – Not for Direct Reuse”
   • Collection date
   • Approximate composition (if known)
   • Operator initials
3. Use color-coded labels (e.g., orange for mixed waste solvents).

5.3 Storage and Temporary Holding

1. Store mixed solvent drums in a designated area with:
   • Secondary containment
   • Proper ventilation
   • Firefighting equipment
2. Maintain daily checks for drum integrity, leaks, or venting issues.

5.4 Processing or Disposal

1. Depending on composition, route streams to:
   • In-house distillation (if possible)
   • Third-party disposal (CPCB-approved)
   • Incineration (if hazardous)
2. Document the fate of each drum in the “Solvent Disposal/Recovery Log” (Annexure-2).

5.5 Documentation and Records

1. Ensure real-time entry of collected volumes, disposal route, and handling personnel.
2. QA must review logs monthly and sign off.
3. 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

1. Mixed Solvent Register (Annexure-1)
2. 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