Procedure for Conducting CIP (Clean in Place) in Machines
| Department | Production/Engineering/Quality Assurance (QA) |
|---|---|
| SOP No. | SOP/Ointment/047 |
| Supersedes | V 1.0 |
| Page No. | Page X of Y |
| Issue Date | [Insert Issue Date] |
| Effective Date | [Insert Effective Date] |
| Review Date | [Insert Review Date] |
1. Purpose
The purpose of this Standard Operating Procedure (SOP) is to define a systematic process for conducting Clean-In-Place (CIP) in manufacturing machines used in ointment production. Proper CIP ensures equipment cleanliness, prevents contamination, and maintains GMP compliance.
2. Scope
This SOP applies to all personnel responsible for handling, operating, and maintaining CIP systems in ointment manufacturing equipment.
3. Responsibilities
- Production Supervisor: Ensures CIP is performed as per schedule.
- Machine Operator: Initiates and monitors the CIP cycle.
- Quality Assurance (QA) Personnel: Verifies cleanliness and maintains records.
- Engineering Technician: Conducts preventive and corrective maintenance on CIP systems.
4. Accountability
The Production and QA Managers are accountable for ensuring that CIP operations comply with GMP standards and are properly documented.
5. Procedure
5.1 Pre-CIP Preparations
- Ensure that the machine is empty and free from product residue.
- Verify that the cleaning solution and water supply are sufficient for the CIP cycle.
- Ensure that all valves, hoses, and drain outlets are properly connected.
5.2 Selecting the CIP Cycle
- Choose the appropriate CIP cycle based on equipment type and residue level:
- Single-Pass CIP: Suitable for low-contamination equipment.
- Recirculating
CIP: Used for heavily contaminated equipment.
Final Rinse CIP: Ensures removal of residual cleaning agents.
5.3 Conducting the CIP Process
5.3.1 Pre-Rinse
- Flush the system with purified water at 40°C–50°C.
- Continue rinsing until all visible residues are removed.
5.3.2 Cleaning Solution Circulation
- Circulate an approved cleaning solution (e.g., sodium hydroxide 1%) at 60°C–80°C.
- Maintain circulation for a minimum of 20 minutes.
- Check for complete dissolution of residues.
5.3.3 Intermediate Rinse
- Flush the system with purified water to remove cleaning agent residues.
- Verify the pH of the rinse water to confirm neutralization.
5.3.4 Final Sanitization
- Circulate a sanitizing agent (e.g., 70% ethanol or peracetic acid solution) for 10 minutes.
- Ensure the sanitizer reaches all contact surfaces.
5.3.5 Final Rinse
- Perform a final rinse with purified water until no cleaning agent residues remain.
- Collect and test rinse samples to ensure compliance with cleaning validation.
5.4 Post-CIP Checks
- Inspect the equipment for any remaining residues.
- Verify conductivity, pH, and microbial limits of the final rinse water.
- Document all parameters in the CIP Log.
5.5 Cleaning Validation
- QA must verify and approve the cleaned equipment before production restart.
- Perform periodic swab testing to confirm the absence of contaminants.
6. Abbreviations
- GMP – Good Manufacturing Practices
- QA – Quality Assurance
- QC – Quality Control
- CIP – Clean-In-Place
- BMR – Batch Manufacturing Record
7. Documents
- CIP Log (Annexure-1)
- Cleaning Validation Report (Annexure-2)
8. References
- WHO GMP Guidelines for Pharmaceutical Manufacturing
- 21 CFR Part 211 – Current Good Manufacturing Practices
- ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
9. SOP Version
Version 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: CIP Log
| Date | Equipment ID | CIP Cycle Type | Cleaning Solution Used | Final Rinse pH | Verified By |
|---|---|---|---|---|---|
| 01/02/2025 | CIP-101 | Recirculating | Sodium Hydroxide 1% | 7.0 | QA Officer |
| 02/02/2025 | CIP-102 | Single-Pass | Peracetic Acid 0.2% | 6.8 | QA Officer |
Annexure-2: Cleaning Validation Report
| Date | Equipment ID | Swab Test Result | Microbial Limits | Final Status | Approved By |
|---|---|---|---|---|---|
| 01/02/2025 | CIP-101 | Pass | Within Limit | Approved | QA Head |
| 02/02/2025 | CIP-102 | Pass | Within Limit | Approved | QA Head |
12. Revision History:
| Revision Date | Revision No. | Details of Revision | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Version | New SOP | QA Head |
| 01/02/2025 | 2.0 | Updated SOP Format | Standardization of Document | QA Head |