Standard Operating Procedure for Screening and Milling of Granules for Tablets

Department	Tablet
SOP No.	SOP/TAB/005/2025
Supersedes	SOP/TAB/005/2022
Page No.	Page 1 of 8
Issue Date	05/03/2025
Effective Date	10/03/2025
Review Date	05/03/2026

1. Purpose

To outline the procedure for screening and milling granules for tablet manufacturing, ensuring uniform particle size distribution and optimal processing for the subsequent tablet compression step.

2. Scope

This SOP applies to the screening and milling of granules following granulation, including the use of sieves and mills to achieve the desired granule size and uniformity for tablet production.

3. Responsibilities

• Manufacturing Personnel: Operate the screening and milling equipment, ensuring granules meet size specifications.
• Quality Control (QC): Perform checks on granule size, particle uniformity, and moisture content to ensure quality standards are met.
• Quality Assurance (QA): Oversee compliance with SOP and ensure all equipment is operating within regulatory requirements.

4. Accountability

The Production Manager is accountable for the proper operation of the screening and milling equipment. The QA Manager ensures compliance with this SOP and GMP standards.

5. Procedure

5.1 Equipment Preparation

1. Inspect all screening and milling equipment, including sieves, mills, and any auxiliary components, to ensure they are clean, calibrated, and in proper working condition.
2. Check that the sieves are correctly sized for the required granule particle size, and verify that milling equipment is free from residue from previous batches.
3. Ensure the area around the equipment is clean and organized to prevent cross-contamination between materials.

5.2 Granule Screening

1. Transfer the granules from the granulation process into the screening area.
2. Place the appropriate sieve or mesh size into the screening equipment to achieve the desired particle size for the granules.
3. Use mechanical vibration or manual agitation to pass the granules through the sieve, ensuring the larger and smaller particles are separated effectively.
4. Discard oversized and undersized granules, and collect the properly sized granules for the next processing step.
5. Monitor the process for uniformity, and adjust equipment settings if necessary to ensure consistency in granule size distribution.

5.3 Granule Milling

1. Transfer the screened granules into the milling equipment (e.g., oscillating granulator or hammer mill).
2. Adjust the milling settings, including the mesh size of the screen or sieve used within the mill, to achieve the desired particle size.
3. Begin milling the granules, and monitor the granule size distribution to ensure it falls within the required specifications for tablet compression.
4. Periodically check the size of the milled granules to ensure uniformity and the desired consistency. Take samples for QC testing if necessary.
5. Stop milling once the required granule size is achieved, and proceed with the next steps in the tablet manufacturing process.

5.4 In-Process Quality Control

1. After screening and milling, perform in-process checks on granule size and particle uniformity.
2. Test a sample of the granules for moisture content using a moisture analyzer, ensuring it falls within the required specifications.
3. Document all quality control test results and observations in the batch record and QC log (Annexure-1).
4. If granule size or moisture content does not meet specifications, evaluate the process and make necessary adjustments to the equipment or procedure.

5.5 Equipment Shutdown and Cleaning

1. After completing the screening and milling process, turn off the equipment and clean the sieves, mills, and other components according to the cleaning SOP.
2. Ensure all equipment is thoroughly cleaned to prevent contamination in future batches. Remove any leftover granules from the equipment and dispose of them according to the waste disposal procedure.
3. Record the cleaning and maintenance activities in the equipment log to ensure traceability and compliance with GMP guidelines.

5.6 Documentation and Record-Keeping

1. Record all operational steps in the batch record, including equipment settings, granule sizes, and in-process checks.
2. Document any deviations from the standard process and actions taken to correct them.
3. Sign off on the batch record to confirm that the screening and milling process was completed in compliance with the SOP.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Granule Screening and Milling Batch Record (Annexure-1)
2. Granule Quality Control Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Granule Screening and Milling Batch Record

Batch Number	Material Name	Screening Mesh Size	Milling Equipment	Granule Size	Moisture Content	Remarks
Batch 001	Material A	0.8 mm	Oscillating Granulator	75% < 500 µm	4.5%	Within Specifications
Batch 002	Material B	1.0 mm	Hammer Mill	80% < 500 µm	5.0%	Minor Deviations

Annexure-2: Granule Quality Control Log

Batch Number	Test Performed	Result	Test Date	QC Personnel
Batch 001	Granule Size	Pass	05/03/2025	John Doe
Batch 002	Moisture Content	Pass	06/03/2025	Jane Smith

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 Granule Size Specifications	Standardization of Screening and Milling Process	QA Head