working condition, calibrated, and ready for use.

4. Accountability

The Production Manager is accountable for ensuring the fluidized bed granulation process is carried out as per this SOP. The QA Manager ensures that the process is validated, the equipment is functioning optimally, and the batch records are complete and accurate.

5. Procedure

5.1 Pre-Granulation Preparation

1. Ensure that all raw materials (active ingredients, excipients, and binders) are available and meet the required specifications.
2. Verify that the fluidized bed granulator is clean and free from contamination from previous batches. Perform the necessary cleaning procedures according to the equipment cleaning SOP.
3. Check that all components of the fluidized bed granulator, such as the air compressor, fluidizing plate, and spray nozzle, are functioning correctly and are in good condition.
4. Review the formulation and batch records to ensure the granulation parameters, such as binder concentration, granule size, and drying time, are defined.

5.2 Granulation Process

1. Load the dry powder blend into the fluidized bed granulator, ensuring that the material is evenly distributed.
2. Start the fluidizing air system to ensure that the material is fluidized and evenly distributed across the bed.
3. Begin spraying the binder solution onto the powder mixture. Ensure that the binder is added slowly and evenly to promote uniform granule formation. The binder solution should be prepared according to the formulation.
4. Monitor the granule formation by checking the particle size distribution and texture of the granules. Adjust the spray rate and fluidizing air pressure if necessary to achieve the desired granule characteristics.
5. If clumping or poor granule formation is observed, adjust the binder solution concentration or spray rate and continue to monitor the process until the desired granule quality is achieved.

5.3 Drying Process

1. Once the granules have reached the desired size, begin the drying phase by activating the drying system. Ensure the air temperature is set according to the product specifications (typically 40-60°C, depending on the material).
2. Monitor the drying process carefully to prevent over-drying or under-drying. Use a moisture analyzer to periodically check the moisture content of the granules to ensure they are within the required specifications.
3. If necessary, adjust the air temperature or airflow rate to achieve uniform drying. The drying time should be optimized to preserve the physical properties of the granules.

5.4 Granule Screening

1. After drying, screen the granules to remove any oversized or undersized particles. Use an appropriate mesh size sieve based on the desired granule size distribution.
2. Check the flow properties and bulk density of the granules. If necessary, add a lubricant (such as magnesium stearate) to improve flowability and compressibility for tablet formation.
3. Ensure that the granules meet the required specifications for tablet compression, including uniformity of size and moisture content.

5.5 Granulation Parameter Optimization

1. If the granulation process does not yield the desired granule characteristics, optimize the parameters by adjusting the binder concentration, spray rate, fluidizing air pressure, or drying conditions.
2. After adjustments, perform test runs to verify that the granules meet the desired specifications. Record all changes and test results in the batch record (Annexure-1).
3. Once optimized, document the final granulation parameters and ensure they are applied consistently in future batches.

5.6 Post-Granulation Inspection

1. Inspect the granules for uniformity, texture, and particle size distribution. Check for any signs of over-drying, under-drying, or clumping.
2. Verify that the granules meet the required specifications for hardness, flowability, and moisture content.
3. If the granules pass all specifications, approve the batch for the next stage of tablet manufacturing (e.g., compression).

5.7 Documentation and Record-Keeping

1. Document all granulation parameters, adjustments, test results, and batch observations in the batch record (Annexure-1).
2. Ensure that all changes to the process are recorded in the deviation report (Annexure-2) along with corrective actions taken.
3. Store all records for the required retention period and ensure they are readily accessible for future audits or regulatory inspections.

5.8 Post-Granulation Equipment Cleaning

1. After the granulation process, clean the fluidized bed granulator according to the equipment cleaning SOP to prevent contamination between batches.
2. Perform routine maintenance checks on the fluidized bed granulator, including inspecting and replacing any worn or damaged parts.
3. Document all cleaning and maintenance activities in the maintenance log (Annexure-3).

6. Abbreviations

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

7. Documents

1. Batch Record (Annexure-1)
2. Deviation Report (Annexure-2)
3. Maintenance Log (Annexure-3)

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: Batch Record

Batch Number	Granulation Type	Binder Type	Granule Testing Results	Comments
Batch 001	Fluidized Bed	PVP	Pass: Particle size, moisture content	No deviations
Batch 002	Fluidized Bed	PVA	Pass: Bulk density, flow properties	Minor adjustments made to binder concentration

Annexure-2: Deviation Report

Deviation Date	Batch Number	Deviation Description	Corrective Action	Responsible Person
15/09/2025	Batch 003	Granules too wet	Reduced binder solution rate	John Doe

Annexure-3: Maintenance Log

Maintenance Date	Equipment Component	Maintenance Performed	Performed By	Comments
12/09/2025	Fluidized Bed Granulator	Cleaning, Inspection	Jane Smith	No issues found, cleaned and calibrated

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 Granulation Parameters	Improved Granule Consistency	QA Head