manages documentation.

4. Accountability

Head – Quality Assurance is accountable for approval, oversight, and ensuring cleaning validation is performed as per applicable GMP and regulatory requirements.

5. Procedure

5.1 Preparation and Planning

1. Develop and approve a cleaning validation protocol prior to execution.
2. Select target product, worst-case product, and common equipment for evaluation.
3. Identify critical sampling locations based on equipment design and residue risk.

5.2 Execution

1. Perform cleaning of the tube filling machine as per the approved cleaning SOP.
2. After cleaning, take rinse and swab samples from identified critical locations (e.g., nozzle, hopper, valves, tube holder).
3. Label and document samples with date, time, and location.
4. Submit samples to QC for analysis within the defined hold time.

5.3 Analytical Testing

1. Analyze samples for active ingredient residues using validated analytical methods.
2. Determine levels of Total Organic Carbon (TOC) and conduct visual inspection.
3. Calculate residue limits based on therapeutic dose or PDE approach per EMA/FDA guidance.

5.4 Acceptance Criteria

1. Residue levels should be below the Maximum Allowable Carryover (MACO) limit.
2. No visible residue on equipment surfaces.
3. Microbiological limits must comply with specifications if applicable.

5.5 Documentation

1. Prepare a validation report summarizing protocol execution, results, deviations (if any), and conclusions.
2. QA and Production must jointly review and approve the report.
3. Submit final report to QA for archival and regulatory readiness.

5.6 Revalidation

1. Perform revalidation in the event of major change in equipment, product, cleaning method, or failure during routine cleaning verification.
2. Revalidation frequency must be defined in the Validation Master Plan (VMP).

6. Abbreviations

• MACO: Maximum Allowable Carryover
• TOC: Total Organic Carbon
• VMP: Validation Master Plan
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. Cleaning Validation Protocol – Annexure-1
2. Cleaning Validation Report – Annexure-2
3. Swab and Rinse Sample Data Sheet – Annexure-3
4. QC Analytical Report – Annexure-4
5. Equipment Cleaning Log

8. References

• FDA Guide to Cleaning Validation
• EMA Guideline on Setting Health-Based Exposure Limits
• ICH Q7: GMP for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Jr. Production Chemist	QA Executive	Head – Manufacturing
Department	Gel Manufacturing	Quality Assurance	Manufacturing

11. Annexures

Annexure-1: Cleaning Validation Protocol Template

(Attach approved protocol with sample plan and acceptance criteria)

Annexure-2: Cleaning Validation Report Format

(Attach final summary report including analytical results and conclusions)

Annexure-3: Swab and Rinse Sample Data Sheet

Sample ID	Location	Time	Date	Test Performed	Result	Limit

Annexure-4: QC Analytical Report Summary

(Attach QC lab report summary with chromatograms if applicable)

Revision History

Revision Date	Revision No.	Change Description	Reason	Approved By
01/04/2022	1.0	Initial Issue	New Equipment Validation	QA Head
09/06/2025	2.0	Updated per EMA guideline and added Annexure-4	Annual Review	QA Head