reports.
Validation Team: Develops and prepares cleaning validation protocols, conducts validation activities, and prepares the cleaning validation report.
Production Supervisors: Ensure that operators follow the validated cleaning procedures, collect the necessary samples, and document the process correctly.
Maintenance Personnel: Ensure that the tablet compression machine is properly maintained and calibrated for effective cleaning and operation.

4) Procedure

The following steps should be followed for cleaning validation of tablet compression machines:

1. Protocol Preparation:
1.1 Develop a cleaning validation protocol that includes the following components:
– A description of the tablet compression machine(s) to be cleaned and validated.
– The objectives of the cleaning validation (e.g., confirming the effectiveness of the cleaning process, ensuring that residual API levels meet acceptance criteria).
– The cleaning procedures to be validated, including cleaning agents, cleaning methods, and equipment used.
– The sampling methods (e.g., swab sampling, rinse sampling), frequency of sampling, and sample locations on the tablet compression machine.
– The test methods to be used, including analytical techniques for residue and microbial testing.
– The acceptance criteria for each test (e.g., acceptable limits for API residues, microbial contamination, cleaning agent residues).
1.2 Ensure that the cleaning validation protocol is reviewed and approved by QA, regulatory affairs, and production management before execution.
1.3 Any changes to the protocol must be documented and reviewed according to the change control process.

2. Cleaning Procedure:
2.1 Perform the cleaning of the tablet compression machine as per the validated cleaning procedure, including disassembly (if necessary), cleaning, and reassembly.
2.2 Ensure that the cleaning process removes all residues from the machine surfaces that come into contact with the tablets, including the die punches, hopper, and tablet press parts.
2.3 Use the validated cleaning agents at the prescribed concentrations and under the specified conditions (e.g., temperature, contact time).
2.4 After cleaning, ensure that all surfaces are dried and prepared for testing.

3. Sampling and Testing:
3.1 Collect samples using the approved sampling methods. This may include swab sampling of critical areas or rinse sampling from equipment parts such as the hopper or compression tooling.
3.2 Use appropriate materials (e.g., sterile wipes or swabs, appropriate solvents) for collecting swab samples.
3.3 Ensure that sampling sites are selected based on potential residue accumulation, focusing on areas where the product comes into direct contact with the machine.
3.4 Perform microbiological testing, chemical residue analysis (e.g., HPLC for API residues), or other relevant tests to verify cleaning effectiveness.
3.5 Document all test results, including sample IDs, the analytical methods used, and the results of each test, ensuring that they meet the predefined acceptance criteria.

4. Report Preparation:
4.1 Prepare a cleaning validation report that includes the following sections:
– Introduction: Overview of the cleaning validation activity, including the objectives, scope, and cleaning procedures validated.
– Methods and Procedures: Detailed description of the cleaning process, including cleaning agents, methods, and sampling techniques used.
– Test Results: Documentation of the results from all testing (residue levels, microbiological results), including a comparison to the acceptance criteria.
– Deviations: A description of any deviations from the protocol, including the root cause analysis and corrective actions taken.
– Conclusion: A summary of the findings, including confirmation that the cleaning process meets the acceptance criteria and is validated for routine use.
4.2 Ensure that the cleaning validation report is reviewed and approved by the validation team and QA before it is finalized.
4.3 Submit the final report for approval by QA, production management, and regulatory affairs.

5. Documentation and Record Keeping:
5.1 Ensure that all cleaning validation documentation, including protocols, test results, and reports, is signed and dated by the responsible personnel.
5.2 Maintain all cleaning validation records in a secure and organized system that allows for easy retrieval during audits or inspections.
5.3 Retain records for the required period in accordance with regulatory guidelines or internal policies.
5.4 Ensure that archived records are protected from damage or loss and are accessible for inspection when needed.

5) Abbreviations

• API: Active Pharmaceutical Ingredient
• QA: Quality Assurance
• GMP: Good Manufacturing Practice
• SOP: Standard Operating Procedure

6) Documents

• Cleaning Validation Protocol
• Cleaning Validation Report
• Test Data and Results
• Deviation and Corrective Action Reports
• Approval Forms
• Archiving and Retention Records

7) Reference

• FDA Guidance for Industry: Equipment Cleaning and Sanitation
• International Council for Harmonisation (ICH) Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
• ISO 9001: Quality Management Systems – Requirements
• USP Chapter 1072: Cleaning and Sanitization of Manufacturing Equipment

8) SOP Version

Version 1.0 – Effective Date: DD/MM/YYYY

Annexure

Template 1: Cleaning Validation Report Template

Report ID	Version	Date	Prepared By	Reviewed By	Approved By
Report ID	Version	DD/MM/YYYY	Prepared By	Reviewed By	Approved By

Template 2: Deviation Report Template

Deviation ID	Deviation Description	Root Cause	Corrective Actions	Follow-Up
Deviation ID	Deviation Description	Root Cause	Corrective Actions	Follow-Up