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
- Identify product changeover, worst-case product, shared equipment, and sampling locations.
- Prepare and approve a cleaning validation protocol for:
- Equipment type
- Cleaning method
- Acceptance limits
- Sampling plan
5.2 Cleaning Process Execution
- Clean the equipment as per the approved cleaning SOP.
- Record all details in the cleaning checklist and cleaning logbook.
- Allow equipment to dry and label as “Cleaned — Awaiting Sampling.”
5.3 Sampling Procedure
- Swab or rinse sampling shall be performed by trained QC personnel.
- Swab locations must represent worst-case areas:
- Dead corners
- Scratches or weld joints
- Difficult-to-clean parts
- Record swab area (usually 25 cm²) and location in the “Cleaning Validation Sampling Log” (Annexure-1).
- Submit samples to QC for analysis within defined hold time.
5.4 Analytical Testing and Limits
- Analyze samples for:
- Active ingredient residue
- Detergent residue
- Microbial contamination (if required)
- 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
- Compile all test data, raw results, and equipment details in the Cleaning Validation Report (Annexure-2).
- QA to review, approve, and archive the report.
- 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
- Cleaning Validation Sampling Log (Annexure-1)
- Cleaning Validation Report Template (Annexure-2)
- 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 |