Standard Operating Procedure for Blend Homogeneity Check During Granulation
| Department | Quality Control |
|---|---|
| SOP No. | SOP/TAB/126/2025 |
| Supersedes | SOP/TAB/126/2022 |
| Page No. | Page 1 of 6 |
| Issue Date | 01/03/2026 |
| Effective Date | 06/03/2026 |
| Review Date | 01/03/2027 |
1. Purpose
To define the procedure for checking the homogeneity of the blend during the granulation process, ensuring that the active pharmaceutical ingredient (API) and excipients are uniformly distributed throughout the blend.
2. Scope
This SOP applies to the monitoring and verification of blend homogeneity during the granulation process, ensuring that the resulting mixture is uniform and consistent for further tablet manufacturing stages.
3. Responsibilities
- Quality Control (QC): Responsible for collecting samples from the granulation process and conducting blend homogeneity tests to ensure uniform distribution of ingredients.
- Granulation Operator: Responsible for performing the granulation process according to established parameters and ensuring that samples are taken for testing at the appropriate stages.
- Quality Assurance (QA): Ensures that blend homogeneity checks are performed according to this SOP and that the results meet the required specifications for consistency and uniformity.
4. Accountability
The QC Manager is accountable for ensuring that blend homogeneity checks are performed accurately and in accordance with this SOP. The QA Manager is responsible for reviewing the results and ensuring compliance with regulatory and internal standards.
5. Procedure
5.1 Sample Collection
- During the granulation process, collect samples from various points in the batch at regular intervals (typically every 10–15 minutes or after processing each set of granules).
- Collect a sufficient quantity of sample to provide a representative measure of the entire batch (at least 100 grams of the blend).
5.2 Blend Homogeneity Test
- Perform a homogeneity test to measure the uniformity of the blend. Typically, this involves the sampling of the blend and testing for uniformity of the active pharmaceutical ingredient (API) and excipient distribution.
- One common method for homogeneity testing is the use of content uniformity tests, which involve measuring the API content in each sample and comparing it to the required specifications.
- Ensure that the sample is adequately mixed and that no stratification or separation of the ingredients has occurred.
- Record the results for each sample, including the API content, and compare it to the target value to assess uniformity.
5.3 Sampling Method
- Follow the sampling plan that dictates the number of samples to be taken, the sampling locations, and the frequency of sampling.
- Ensure that the samples are taken from various parts of the batch (e.g., top, middle, and bottom) to represent the entire blend.
- If any sample results deviate from the target API content beyond the acceptable range (typically ±5% of the target), further investigation and adjustments to the granulation process should be performed.
5.4 Monitoring and Adjustments
- If the blend homogeneity does not meet the required standards, adjustments to the granulation process must be made. This could include modifying mixing times, granulator speed, or other granulation parameters to improve blend uniformity.
- Re-sample and retest after process adjustments to verify that the blend homogeneity has improved.
5.5 Documentation
- Record all results of the blend homogeneity tests, including sample numbers, test results, and any corrective actions taken, in the batch record (Annexure-2).
- Document any deviations from the specified homogeneity criteria and the corresponding corrective actions in the deviation report (Annexure-1).
- Ensure that all records are signed and dated by the responsible personnel and reviewed by QA to confirm compliance with quality standards.
5.6 Acceptance Criteria
- The blend homogeneity test should meet the following acceptance criteria:
- The content of the API in each sample should be within ±5% of the target content.
- The overall blend should exhibit uniform distribution without any significant segregation or stratification of the API and excipients.
- If the results fall outside the specified range, the batch may be rejected or reworked, and corrective actions should be documented in the deviation report (Annexure-1).
5.7 Post-Granulation Actions
- Once the blend homogeneity is confirmed, proceed with the next steps in tablet manufacturing, such as compression, coating, and packaging.
- Ensure that any adjustments made to the granulation process are recorded, and that the equipment is cleaned and calibrated as required.
6. Abbreviations
- SOP: Standard Operating Procedure
- GMP: Good Manufacturing Practice
- QC: Quality Control
- QA: Quality Assurance
- API: Active Pharmaceutical Ingredient
7. Documents
- Batch Record (Annexure-2)
- Deviation Report (Annexure-1)
8. References
- USP <905> – Content Uniformity
- 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
- European Pharmacopoeia (EP) – Specifications for Blend Homogeneity Testing
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Deviation Report
| Deviation Date | Batch Number | Deviation Description | Corrective Action | Responsible Person |
|---|---|---|---|---|
| 15/12/2025 | Batch 001 | API content deviation in 3% of samples | Adjusted granulation speed and re-sampled | John Doe |
Annexure-2: Batch Record
| Sample Number | API Content (%) | Average API Content (%) | Deviation (%) | Action Taken |
|---|---|---|---|---|
| Sample 1 | 99.5 | 99.6 | ±0.5% | Accepted |
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 sampling and testing procedures | Improved uniformity checking | QA Head |