Standard Operating Procedure for Cleaning of Manufacturing Equipment in API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/037/2025
Supersedes	SOP/API/037/2022
Page No.	Page 1 of 11
Issue Date	13/04/2025
Effective Date	15/04/2025
Review Date	13/04/2026

1. Purpose

To define the procedure for cleaning manufacturing equipment used in the production of Active Pharmaceutical Ingredients (APIs), ensuring removal of product residues, cleaning agents, and microbial contamination, thereby preventing cross-contamination.

2. Scope

This SOP applies to all major and auxiliary equipment used in API manufacturing processes, including reactors, centrifuges, filters, dryers, blenders, mills, and associated transfer lines.

3. Responsibilities

• Production Operator: Execute cleaning activities as per the approved cleaning procedure.
• QA Officer: Verify cleaning status, approve equipment for reuse, and maintain cleaning records.
• Engineering: Maintain cleaning utilities and ensure equipment is in proper working condition.

4. Accountability

The Production Head is accountable for ensuring cleaning procedures are followed. QA Head is responsible for verification and compliance with GMP cleaning standards.

5. Procedure

5.1 Cleaning Types

• Product-to-Product Cleaning: Between different product batches.
• Batch-to-Batch Cleaning: Between consecutive batches of same product (if required).
• Periodic Cleaning: At defined intervals even if not used.

5.2 Pre-Cleaning Checks

1. Ensure equipment is shut down, disconnected from utilities, and cooled.
2. Wear appropriate PPE (gloves, goggles, apron, mask).
3. Verify that waste material has been removed from the equipment.
4. Collect and dispose of cleaning residues in accordance with waste SOPs.

5.3 Cleaning Procedure

1. Use approved cleaning agents as per respective cleaning SOP (alkaline, acidic, or neutral detergent).
2. Wash equipment surfaces with potable water followed by detergent cleaning.
3. Use brushes, lint-free cloths, or spray balls depending on equipment size and shape.
4. Rinse with purified water until the rinse sample meets acceptable limits for:
   • pH
   • Conductivity
   • Residue (visual and chemical)
5. Dry the equipment with clean air or lint-free wipes.
6. Label equipment as “Cleaned” with cleaning date, time, and operator initials.

5.4 Cleaning Verification

1. Perform swab or rinse testing for:
   • Active ingredient residue
   • Cleaning agent residue
   • Microbial bioburden (if applicable)
2. Use validated analytical methods and refer to established acceptance limits.
3. Document results in the “Cleaning Verification Log” (Annexure-1).

5.5 Equipment Release

1. QA to review cleaning and test results.
2. Label equipment as “Ready for Use” upon approval.
3. Record equipment status in “Equipment Cleaning Status Log” (Annexure-2).

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• API: Active Pharmaceutical Ingredient
• PPE: Personal Protective Equipment

7. Documents

1. Cleaning Verification Log (Annexure-1)
2. Equipment Cleaning Status Log (Annexure-2)
3. Swab Test Report (Annexure-3)

8. References

• ICH Q7 – Good Manufacturing Practice for APIs
• 21 CFR Part 211 – Subpart D (Equipment)
• WHO TRS 986, Annex 2 – Cleaning Validation Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Cleaning Verification Log

Date	Equipment ID	Product Name	Swab/Rinse	Result	Reviewed By
13/04/2025	R-105	API-X	Swab	Complies

Annexure-2: Equipment Cleaning Status Log

Equipment ID	Cleaning Date	Next Use	Status	QA Approval
R-105	13/04/2025	14/04/2025	Ready

Annexure-3: Swab Test Report

Location	Surface Area (cm²)	Analyte	Result (ppm)	Limit	Status
Inner Reactor Wall	25	API-X	0.5	≤1.0	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial Issue	New Equipment SOP	QA Head
13/04/2025	2.0	Expanded scope, added verification logs	Regulatory compliance	QA Head