Scope

This SOP is applicable to all equipment used in sterile injectable manufacturing including solution preparation tanks, mixing vessels, filters, lyophilizers, and filling machines that undergo cleaning prior to reuse.

3. Responsibilities

• Production Operator: Executes cleaning procedures and performs visual inspection.
• QA Executive: Conducts swab sampling and verifies visual inspection.
• QC Analyst: Performs analytical tests for residue detection such as TOC, conductivity, and specific chemical analysis.
• Engineering Technician: Assists in cleaning validation equipment and calibration.

4. Accountability

The Head of Quality Assurance is accountable for ensuring this SOP is followed and that all cleaning verifications are conducted before equipment reuse.

5. Procedure

5.1 Visual Inspection

1. Post-cleaning, the production operator must perform a thorough visual inspection under adequate lighting.
2. Check all internal surfaces, joints, nozzles, and ports for any residue, discoloration, or foreign matter.
3. Document findings in the Equipment Cleaning Checklist (Annexure-1).
4. QA to perform a second-level visual check to verify cleanliness.

5.2 Swab Sampling

1. Identify sampling points based on worst-case locations (e.g., dead legs, crevices).
2. Use pre-validated sterile swabs moistened with WFI to swab an area of 25 cm².
3. Place swabs in sterile containers, label with equipment ID and sampling point.
4. Submit to QC laboratory for chemical and microbial testing.

5.3 Rinse Sampling

1. If swab sampling is not feasible, collect rinse samples from final WFI rinse after cleaning.
2. Collect at least 100 mL in sterile containers and label appropriately.
3. Submit for TOC, conductivity, and chemical residue analysis.

5.4 Analytical Testing

• Test samples against predefined acceptance criteria:
  • TOC: < 500 ppb
  • Conductivity: < 1.3 µS/cm
  • API-specific limits: As per cleaning validation protocol
  • Microbial limits: < 10 CFU/100 cm²
• Document test results in the Residue Testing Log (Annexure-2).

5.5 Verification and Documentation

1. QA must review all test reports and visual inspection records.
2. If results comply with acceptance criteria, QA will sign the Equipment Release Form (Annexure-3).
3. Equipment shall be labeled as “Cleaned and Ready for Use.”
4. All records must be archived in the cleaning validation file for traceability.

5.6 Deviation Handling

1. If residue is found above limits:
   • Repeat cleaning process immediately.
   • Investigate root cause using deviation form.
   • Record corrective and preventive actions.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• QC: Quality Control
• WFI: Water for Injection
• TOC: Total Organic Carbon
• CFU: Colony Forming Units
• ID: Identification

7. Documents

1. Annexure-1: Equipment Cleaning Checklist
2. Annexure-2: Residue Testing Log
3. Annexure-3: Equipment Release Form

8. References

• ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• FDA Guidance on Cleaning Validation
• WHO Technical Report Series No. 937

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Manufacturing Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Equipment Cleaning Checklist

Date	Equipment ID	Visual Inspection Status	Operator	QA Reviewer
23/06/2025	MLT-05	Clean	Ravi Patel	Sunita Reddy

Annexure-2: Residue Testing Log

Sample ID	TOC (ppb)	Conductivity (µS/cm)	CFU	Status	Analyst
MLT05-R1	92	1.1	1	Pass	Vinay Kumar

Annexure-3: Equipment Release Form

Equipment ID	Cleaning Status	QA Approval	Date	Remarks
MLT-05	Approved	Sunita Reddy	23/06/2025	Ready for use

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
12/03/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Updated criteria and added Annexures	Annual Review	QA Head