compliance with GMP.

2. Scope

This procedure is applicable to all CIP systems installed in the sterile injectable manufacturing area for the cleaning of solution preparation tanks, transfer lines, holding vessels, and related piping components.

3. Responsibilities

• Manufacturing Operator: Operates and monitors CIP cycles.
• Manufacturing Supervisor: Ensures adherence to procedure and reviews logs.
• Quality Assurance: Verifies cleaning effectiveness and approves records.
• Engineering Department: Maintains CIP system equipment and performs calibration.

4. Accountability

Production Head and QA Head are accountable for ensuring SOP compliance and effectiveness of the CIP cleaning cycle.

5. Procedure

5.1 Pre-Cleaning Checks

1. Ensure the CIP system is connected correctly to the equipment to be cleaned.
2. Verify availability of approved cleaning agents and proper concentration.
3. Ensure equipment is free from gross contamination before initiating CIP.
4. Record the pre-cleaning status in the CIP Pre-Cleaning Checklist (Annexure-1).

5.2 CIP Cycle Overview

1. The standard CIP cycle consists of the following steps:
   • Initial Rinse (Water for Injection – WFI)
   • Alkaline Wash with Detergent
   • Intermediate Rinse (Purified Water)
   • Acid Rinse (if applicable)
   • Final Rinse (WFI)
   • Drying (Air/Nitrogen Flush if validated)

5.3 Operating Instructions

1. Turn on the CIP system and set the parameters per the validated CIP recipe loaded in the HMI/SCADA.
2. Verify temperature and flow rate sensors are calibrated and operational.
3. Start the CIP cycle and monitor:
   • Flow rate and pressure (must meet validated specifications)
   • Temperature (e.g., 80°C for hot WFI rinse)
   • Detergent concentration (verified via titration)
   • Cycle timing and sequencing
4. Document all values in the CIP Execution Log (Annexure-2).

5.4 Post-Cleaning Verification

1. Visually inspect equipment for residue, staining, or pooling of cleaning agents.
2. Collect rinse water samples and send to QC for:
   • TOC (Total Organic Carbon)
   • Conductivity
   • Microbial Testing
3. Confirm cleanliness before use in manufacturing. Fill Cleaning Approval Form (Annexure-3).

5.5 Special Considerations

1. Never modify the validated cycle without re-approval.
2. Re-validate the CIP cycle after any significant system changes or new equipment integration.

5.6 Cleaning Frequency

1. Perform CIP after every batch or as per the cleaning schedule.
2. Record all cleaning activities in the Cleaning Schedule Log.

6. Abbreviations

• SOP: Standard Operating Procedure
• CIP: Clean-In-Place
• WFI: Water for Injection
• TOC: Total Organic Carbon
• QC: Quality Control
• HMI: Human Machine Interface

7. Documents

1. CIP Pre-Cleaning Checklist – Annexure-1
2. CIP Execution Log – Annexure-2
3. Cleaning Approval Form – Annexure-3

8. References

• WHO TRS 986 – GMP for Pharmaceutical Products
• 21 CFR Part 211 – US FDA cGMP
• ISPE Baseline Guide for Cleaning Validation

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: CIP Pre-Cleaning Checklist

Checklist Item	Status	Checked By	Date
Line Clearance	Completed	Rajesh Kumar	24/06/2025
Cleaning Agent Available	Yes	Sunita Reddy	24/06/2025

Annexure-2: CIP Execution Log

Parameter	Set Value	Observed Value	Checked By	Date
Rinse Temp (WFI)	80°C	79.5°C	Ajay Verma	24/06/2025
Detergent Flow Rate	100 L/min	102 L/min	Ajay Verma	24/06/2025

Annexure-3: Cleaning Approval Form

Equipment ID	Cleaned On	Inspected By	Approved By	Date
CIP-002	24/06/2025	Ravi Sharma	QA Officer	24/06/2025

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
15/02/2022	1.0	Initial SOP Released	New Installation	QA Head
24/06/2025	2.0	Updated Cycle Parameters & Documentation Flow	Annual Review	QA Head