Cleaning Validation Procedure for Clean-in-Place (CIP) Systems

1. Objective

To establish a validated cleaning procedure for Clean-in-Place (CIP) systems ensuring removal of product residues, cleaning agents, and microbial contaminants to acceptable levels.

2. Scope

Applicable to all CIP systems used in manufacturing equipment such as bioreactors, tanks, pipelines, and filling systems in pharmaceutical/biotech facilities.

3. Responsibilities

• Quality Assurance (QA): Approves cleaning validation protocol and report.

• Production: Performs cleaning operations as per SOP.

• Quality Control (QC): Performs analytical testing for residues and microbial contamination.

• Engineering: Ensures proper functioning of CIP system.

4. Procedure

4.1 Pre-validation Activities

• Identify equipment requiring CIP.

• Select worst-case product, soil, and cleaning agent.

• Define acceptance criteria (e.g., MACO, surface cleanliness, TOC limits).

• Prepare risk assessment and sampling plan.

4.2 Cleaning Process Description

• Pre-rinse: With purified water to remove bulk residues.

• Detergent Wash: Circulation of validated cleaning solution at specified temperature, flow rate, and duration.

• Intermediate Rinse: Purified water rinse to remove cleaning agent.

• Final Rinse: With WFI or purified water until rinse meets conductivity and TOC limits.

• Sanitization (if required): Hot water or chemical sanitization.

4.3 Validation Protocol

• Define number of validation runs (minimum 3 consecutive successful runs).

• Sampling method:

  • Swab Sampling: Critical areas (hard-to-clean surfaces, dead legs, gaskets).

  • Rinse Sampling: For large surface areas and internal pipelines.

• Analytical methods: HPLC, TOC, conductivity, pH, and microbial testing.

• Acceptance criteria:

  • Residual product < calculated MACO.

  • Cleaning agent residues within safe limit.

  • TOC/conductivity/pH within specification.

  • Microbial limits ≤ defined acceptance criteria.

4.4 Revalidation

• Required if equipment modification, new product introduction, or change in cleaning process/agent occurs.

5. Documentation

• Cleaning validation protocol and report.

• Raw data (analytical results, swab/rinse records).

• CIP cycle parameters (temperature, flow rate, time, pressure).

6. Acceptance Criteria Examples

• Residual API < 10 ppm.

• TOC < 500 ppb (unless product-specific limit applies).

• Microbial count < 10 CFU/100 mL rinse water.

• No visible residues.

🎓 Discover one of the best Pharmaceutical Quality Assurance course available —click below to explore the course that’s shaping future Quality Assurance skills.

https://trcjw.on-app.in/app/oc/306166/trcjw