and approves the batch if the blend homogeneity meets specifications.

Production Supervisor: Ensures that all personnel follow the correct procedures for blending and testing homogeneity, and addresses any deviations in the process.

4. Accountability

The Production Manager is accountable for overseeing the blend homogeneity process during direct compression and ensuring the homogeneity of the blend. The QA Manager is responsible for reviewing the test results and ensuring that the process complies with the specifications.

5. Procedure

5.1 Preparation of Blend for Compression

1. Ensure that all ingredients required for the blend are weighed accurately as per the batch record and formulation.
2. Blend the ingredients using the appropriate mixing equipment (e.g., V-blender or high-shear mixer) to achieve a homogeneous blend with uniform distribution of the active pharmaceutical ingredient (API) and excipients.
3. Check the blend for any signs of segregation or clumping, and perform additional mixing if necessary to ensure uniformity.
4. Once the blend is ready, proceed with the sampling for homogeneity testing.

5.2 Sampling for Homogeneity Testing

1. Take samples from different locations of the blend to ensure uniformity. Typically, samples should be taken from at least three different spots in the blend, including the top, middle, and bottom of the batch.
2. Ensure that the sampling procedure is random and covers the entire blend to account for any potential segregation.
3. Each sample should be of sufficient size to allow for representative testing of both the API content and other blend characteristics.
4. Store the samples in a clean, contamination-free container until they are tested.

5.3 Blend Homogeneity Testing

1. Conduct a uniformity of content test to determine the consistency of the API in the blend. This can be done by analyzing the API concentration in the sample using a validated analytical method, such as High-Performance Liquid Chromatography (HPLC) or UV-Visible Spectrophotometry.
2. Check the blend for other critical properties such as flowability, moisture content, and particle size distribution, which can affect homogeneity.
3. Ensure that the test results fall within the established specifications for API content uniformity. The allowable variation for the API content should be specified in the batch record or formulation sheet.
4. If any sample fails the test for uniformity, repeat the blending process and retest the blend until uniformity is achieved.

5.4 Documentation of Results

1. Document all homogeneity testing results, including the sample locations, test methods used, and the test outcomes in the batch record (Annexure-1).
2. Record any deviations or failures, along with corrective actions taken, in the deviation report (Annexure-2).
3. Store all documentation in compliance with the company’s record retention policy and ensure it is accessible for audits and inspections.

5.5 Corrective Actions for Deviations

1. If the blend fails the homogeneity test, investigate the root cause of the failure. Possible causes may include improper mixing time, inadequate mixing speed, or issues with raw material segregation.
2. Implement corrective actions such as adjusting mixing parameters, using different excipients, or re-blending the batch if needed.
3. Retest the batch after corrective actions have been implemented to confirm that the blend now meets the homogeneity specifications.
4. Record the investigation findings and corrective actions in the deviation report (Annexure-2) and batch record (Annexure-1).

5.6 Calibration and Maintenance of Testing Equipment

1. Ensure that all analytical equipment used for testing blend homogeneity, such as HPLC, UV spectrophotometers, and balances, is properly calibrated and maintained according to the manufacturer’s specifications.
2. Document all calibration and maintenance activities in the equipment maintenance log (Annexure-3).

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• API: Active Pharmaceutical Ingredient
• HPLC: High-Performance Liquid Chromatography

7. Documents

1. Batch Record (Annexure-1)
2. Deviation Report (Annexure-2)
3. Equipment 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	Sample Location	API Content	Test Method	Comments
Batch 001	Top, Middle, Bottom	99.5%	HPLC	Blend homogeneous

Annexure-2: Deviation Report

Deviation Date	Batch Number	Deviation Description	Corrective Action	Responsible Person
21/12/2025	Batch 002	API content variation	Re-blended batch and retested	Jane Smith

Annexure-3: Equipment Maintenance Log

Maintenance Date	Equipment	Maintenance Performed	Performed By	Comments
10/12/2025	HPLC	Calibration	John Doe	Calibration verified, no issues found

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 Homogeneity Test Criteria	Improved Test Sensitivity	QA Head