Standard Operating Procedure for Cleaning Validation Between Batches in API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/038/2025
Supersedes	SOP/API/038/2022
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 cleaning validation between batches of different or same products in API manufacturing to ensure the removal of any residual active ingredients, cleaning agents, or microbial contaminants.

2. Scope

This SOP applies to all equipment, containers, and contact parts used in API production that require cleaning validation between batches of the same or different products.

3. Responsibilities

• Production Team: Execute cleaning procedures and document operations.
• QA Department: Approve cleaning validation protocol and report. Ensure adherence to validation plan.
• QC Department: Analyze swab/rinse samples and provide results for assessment.

4. Accountability

The QA Head is accountable for the approval and implementation of the cleaning validation program. The Production Head ensures compliance during manufacturing operations.

5. Procedure

5.1 Cleaning Validation Strategy

1. Identify product changeover, worst-case product, shared equipment, and sampling locations.
2. Prepare and approve a cleaning validation protocol for:
   • Equipment type
   • Cleaning method
   • Acceptance limits
   • Sampling plan

5.2 Cleaning Process Execution

1. Clean the equipment as per the approved cleaning SOP.
2. Record all details in the cleaning checklist and cleaning logbook.
3. Allow equipment to dry and label as “Cleaned — Awaiting Sampling.”

5.3 Sampling Procedure

1. Swab or rinse sampling shall be performed by trained QC personnel.
2. Swab locations must represent worst-case areas:
   • Dead corners
   • Scratches or weld joints
   • Difficult-to-clean parts
3. Record swab area (usually 25 cm²) and location in the “Cleaning Validation Sampling Log” (Annexure-1).
4. Submit samples to QC for analysis within defined hold time.

5.4 Analytical Testing and Limits

1. Analyze samples for:
   • Active ingredient residue
   • Detergent residue
   • Microbial contamination (if required)
2. Compare results with established acceptance criteria:
   • Not more than 10 ppm of previous product (unless otherwise justified)
   • No visible residue
   • Rinse water: pH and conductivity within limits

5.5 Documentation and Validation Report

1. Compile all test data, raw results, and equipment details in the Cleaning Validation Report (Annexure-2).
2. QA to review, approve, and archive the report.
3. Update master cleaning SOP with validated parameters and frequency based on results.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• QC: Quality Control
• ppm: Parts per million
• cm²: Square centimeters

7. Documents

1. Cleaning Validation Sampling Log (Annexure-1)
2. Cleaning Validation Report Template (Annexure-2)
3. Swab Test Analytical Report (Annexure-3)

8. References

• ICH Q7 – GMP Guidelines for API
• 21 CFR Part 211 – Subpart D & E
• WHO TRS 937 – Annex 4 (Cleaning Validation)

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 Validation Sampling Log

Date	Equipment ID	Product	Swab Location	Area (cm²)	Collected By
13/04/2025	DR-101	API-X	Agitator Blade	25

Annexure-2: Cleaning Validation Report Template

Batch No.	Product	Previous Product	Equipment	Validation Status
API-202504	API-X	API-Y	R-205	Pass

Annexure-3: Swab Test Analytical Report

Sample ID	Analyte	Result (ppm)	Limit (ppm)	Status
SWB-101	API-Y	0.7	≤10	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP Release	New Equipment Validation	QA Head
13/04/2025	2.0	Inclusion of microbial testing and revised limits	Audit Findings	QA Head