Standard Operating Procedure for Validation of Cleaning Methods for Capsule Equipment

Department	Capsule Manufacturing
SOP No.	SOP/CM/132/2025
Supersedes	SOP/CM/132/2022
Page No.	Page 1 of 6
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

The purpose of this SOP is to outline the procedures for validating cleaning methods used for capsule manufacturing equipment. Validation ensures that the cleaning methods effectively remove residues, contaminants, and cleaning agents, maintaining product quality and compliance with regulatory standards. This process ensures that cleaning methods consistently deliver reproducible results and prevent contamination in future batches.

2. Scope

This SOP applies to all cleaning methods used for capsule manufacturing equipment, including high-shear mixers, capsule filling machines, granulation equipment, and other equipment used in the manufacturing process. It outlines the steps for validation, including initial validation, revalidation, and the monitoring of cleaning effectiveness over time.

3. Responsibilities

• Quality Assurance (QA) Team: Responsible for overseeing the validation of cleaning methods, reviewing cleaning results, and ensuring that all cleaning processes meet GMP standards.
• Quality Control (QC) Team: Responsible for sampling, testing, and verifying the cleaning effectiveness through residue and contamination testing.
• Production Operators: Responsible for performing the cleaning of equipment and ensuring that the validation procedures are followed during the cleaning process.
• Production Supervisor: Oversees the validation process and ensures that all cleaning methods are validated and documented as per the SOP.
• Maintenance Team: Ensures that equipment is in good working condition and that there are no issues that could affect the cleaning process.

4. Accountability

The Capsule Manufacturing Supervisor is responsible for ensuring the proper validation of cleaning methods as per this SOP. The QA Manager ensures that the validation process complies with GMP requirements and that all relevant documentation is properly reviewed and approved.

5. Procedure

5.1 Preparation for Cleaning Method Validation

Before validating cleaning methods, the following steps must be completed:

1. Review Cleaning Method
   1. Ensure that the cleaning method used for each piece of equipment is documented, and review the cleaning agent’s properties to confirm its effectiveness in removing residues.
   2. Ensure that the cleaning process is conducted as per the manufacturer’s instructions and documented cleaning procedure.
2. Gather Equipment and Materials
   1. Ensure that all necessary materials for cleaning validation are available, including sampling tools, residue testing kits, cleaning agents, and inspection checklists.
   2. Ensure that the cleaning tools and testing materials are calibrated and ready for use in the validation process.
3. Prepare the Validation Plan
   1. Prepare the Cleaning Method Validation Plan (Annexure-1), which outlines the specific equipment, testing methods, and acceptance criteria to be used during validation.
   2. Identify the testing locations and sampling techniques that will be used to ensure that all critical areas of the equipment are cleaned properly.

5.2 Cleaning Method Validation Process

Follow these steps to validate cleaning methods:

1. Perform Initial Cleaning
   1. Perform the cleaning process on the equipment as per the documented cleaning procedure and the cleaning method to be validated.
   2. Ensure that all surfaces are properly cleaned, paying attention to hard-to-reach areas where contamination is most likely to occur.
2. Sampling for Residues
   1. Take samples from various areas of the equipment (such as surfaces, crevices, and equipment parts) after cleaning.
   2. Use swabbing or rinse sampling techniques to collect residue samples for testing. Ensure the sample collection process is consistent and representative of all cleaned surfaces.
3. Analyze Samples for Residues
   1. Send the collected samples to the QC team for testing to detect residues, contaminants, and cleaning agent residues.
   2. Use appropriate analytical methods (such as visual inspection, chemical testing, or microbiological testing) to ensure that no residues are present beyond acceptable limits.
4. Review Results
   1. Review the cleaning validation test results to ensure that all residue levels meet the acceptance criteria defined in the Cleaning Validation Plan (Annexure-1).
   2. If any residues are found above the acceptable limits, corrective actions must be taken, and the cleaning process should be revised and revalidated.
5. Document Results
   1. Document all findings, including cleaning methods, residue test results, corrective actions (if any), and final approval for use of the equipment in the Cleaning Validation Report (Annexure-2).

5.3 Revalidation of Cleaning Methods

Revalidation should be performed under the following circumstances:

1. Change in Cleaning Process
   1. If there is any change in the cleaning process (such as a new cleaning agent or modified cleaning procedure), a revalidation must be conducted to confirm that the new process is effective.
2. New Equipment
   1. When new equipment is added to the production process, the cleaning method must be validated to ensure that the cleaning process is effective for the new equipment.
3. Periodic Revalidation
   1. Periodic revalidation is required at regular intervals (e.g., annually) to ensure that the cleaning method continues to meet the required standards over time.

5.4 Documentation

Ensure that all actions are properly documented for traceability and compliance:

1. Complete Validation Report
   1. Record all validation activities in the Cleaning Method Validation Report (Annexure-2), including the cleaning process, sampling results, acceptance criteria, and any deviations from the established process.
2. Update Cleaning Validation Plan
   1. After the validation process, update the Cleaning Validation Plan (Annexure-1) to reflect any changes made to the cleaning process or methods.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• PPE: Personal Protective Equipment

7. Documents

1. Cleaning Method Validation Report (Annexure-2)
2. Cleaning Validation Plan (Annexure-1)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• Good Manufacturing Practice (GMP) Guidelines

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 Plan

Equipment ID	Cleaning Method	Acceptance Criteria	Testing Locations	Sampling Method
High-Shear Mixer 001	Use of detergent and water	No residual contamination above 10 ppm	Blades, mixing chamber	Swab sampling

Annexure-2: Cleaning Method Validation Report

Batch ID	Validation Date	Operator	Cleaning Method Used	Results	Corrective Actions
Batch 001	02/02/2025	John Doe	Detergent wash and rinse	Passed, no residues found	None

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial version	New SOP Creation	QA Head
01/02/2025	2.0	Updated cleaning method validation process and documentation	Improved clarity and compliance	QA Head