Standard Operating Procedure for Validation of Granulation Processes for Capsules

Department	Capsule Manufacturing
SOP No.	SOP/CM/178/2025
Supersedes	SOP/CM/178/2022
Page No.	Page 1 of 10
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

The purpose of this SOP is to establish a standardized procedure for validating the granulation processes used in capsule manufacturing. Granulation is a crucial step in the production of capsules as it affects the flow, uniformity, and compressibility of the material. This SOP ensures that the granulation process is performed consistently and meets the required quality standards.

2. Scope

This SOP applies to the validation of the granulation process used in the production of capsule fill materials. It covers all aspects of the granulation process, including equipment calibration, material handling, granulation parameters, and performance criteria. This SOP is applicable to both wet and dry granulation processes used in capsule manufacturing.

3. Responsibilities

• Quality Control (QC) Team: Responsible for performing the validation tests on the granulation process and ensuring that all parameters meet the required specifications. They will also ensure that the process remains consistent throughout production.
• Quality Assurance (QA) Team: Responsible for reviewing and approving the granulation process validation results and ensuring compliance with GMP and regulatory requirements.
• Production Team: Ensures that the granulation process is carried out according to the validated parameters during routine production.
• Engineering Team: Responsible for ensuring the proper functioning of granulation equipment and ensuring that it is calibrated and maintained in accordance with regulatory standards.

4. Accountability

The QA Manager is accountable for ensuring that the granulation process is validated and meets all the necessary specifications. The QC Supervisor is responsible for the execution of validation testing and documentation. The Production Supervisor ensures the granulation process is followed correctly during production.

5. Procedure

5.1 Pre-Validation Setup

Before initiating the validation process for the granulation process, ensure the following steps are completed:

1. Review Validation Plan
   1. Review the granulation process validation plan, including the required test parameters, test methods, and acceptance criteria. The plan should be approved by the QA department before starting the validation process.
2. Select Granulation Parameters
   1. Identify the critical process parameters for the granulation process, such as binder concentration, granulation time, drying time, and mixing speed. These parameters should align with established specifications for the capsule formulation.
3. Prepare Granulation Samples
   1. Prepare representative batches of granules to be tested. Ensure the samples are accurately representative of production scale batches and follow the defined specifications for each parameter.
4. Calibrate Equipment
   1. Ensure that all granulation equipment, including mixers, fluidized bed dryers, and sieve machines, are calibrated according to the manufacturer’s instructions. Record the calibration details in the Equipment Calibration Log (Annexure 1).

5.2 Granulation Process Validation

Follow these steps to perform the granulation process validation:

1. Test Batch Preparation
   1. Prepare test batches of granules following the defined granulation process parameters. Ensure that the batch is large enough to test the key performance attributes and replicate real production conditions.
2. Test Critical Process Parameters
   1. Measure and document the following parameters during the granulation process:
      • Binder concentration and distribution
      • Granulation time and mixing speed
      • Granule size distribution
      • Moisture content of the granules
3. Performance Testing of Granules
   1. Test the granules for their flow properties, compressibility, and content uniformity. Ensure that the granules meet the specified standards for uniformity and ease of processing.
4. Drying and Sieving
   1. Dry the granules using the designated drying process (e.g., fluidized bed drying), and test the final moisture content to ensure that it is within acceptable limits.
   2. Sieve the granules to obtain the required particle size range and ensure that the material is suitable for capsule filling.
5. Document Validation Results
   1. Document all results in the Granulation Process Validation Report (Annexure 2). Include data on the test parameters, process performance, and deviations, if any.

5.3 Post-Validation Activities

Once the validation is complete, ensure the following actions are taken:

1. Approval of Results
   1. The QA Manager reviews and approves the validation results to confirm that the granulation process meets all required specifications and is suitable for production.
2. Training of Personnel
   1. Ensure that the production team is trained on the validated granulation process, including all critical parameters and procedures for monitoring during production.
3. Ongoing Monitoring
   1. Establish a routine monitoring program to ensure that the granulation process is consistently followed during production. Perform periodic re-validation studies to ensure continued process performance and stability.
4. Documentation and Record Keeping
   1. Archive all validation documentation, including the study report, calibration records, and training logs, in compliance with regulatory retention requirements.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QA: Quality Assurance
• QC: Quality Control
• R&D: Research and Development
• RH: Relative Humidity

7. Documents

1. Annexure 1: Equipment Calibration Log
2. Annexure 2: Granulation Process Validation Report
3. Annexure 3: Granulation Test Results Log

8. References

• FDA Guidance on Process Validation for Pharmaceutical Products
• Good Manufacturing Practice (GMP) Guidelines
• USP <1225> – Validation of Compendial Methods

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure 1: Equipment Calibration Log

Equipment ID	Calibration Date	Operator	Calibration Details	Next Calibration Due
Granulator 212	01/02/2025	John Doe	Calibration of speed and mixing parameters	01/02/2026

Annexure 2: Granulation Process Validation Report

Batch ID	Validation Date	Test Parameters	Results	Remarks
Batch 001	02/02/2025	Binder concentration, granule size distribution	Pass	Granulation process is stable and meets the criteria

Annexure 3: Granulation Test Results Log

Sample ID	Test Date	Test Type	Results	Deviation
Sample 001	02/02/2025	Granule Size Distribution	Pass	None

12. Revision History

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial version of SOP	Creation of SOP for granulation process validation	QA Head
01/02/2025	2.0	Updated testing parameters and added new validation checks	Inclusion of updated tests and process improvements	QA Head