Standard Operating Procedure for Monitoring Capsule-Fill Density in Production
| Department | Capsule Manufacturing |
|---|---|
| SOP No. | SOP/CM/107/2025 |
| Supersedes | SOP/CM/107/2022 |
| Page No. | Page 1 of 6 |
| 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 the procedure for monitoring the fill density of capsules during the manufacturing process. Ensuring proper fill density is critical for maintaining product consistency, ensuring accurate dosing, and meeting regulatory standards.
2. Scope
This SOP applies to all processes involved in capsule filling, including the preparation of the fill material, monitoring during encapsulation, and verification of fill density for both hard gelatin and soft gelatin capsules.
3. Responsibilities
- Production Operators: Responsible for performing the fill density checks as outlined in this SOP and ensuring the correct fill density is maintained during capsule production.
- Quality Control (QC) Team: Responsible for conducting routine checks of capsule fill density, recording data, and performing corrective actions in case of deviations.
- Quality Assurance (QA) Team: Ensures compliance with the SOP and regulatory requirements. Reviews documentation and test results to verify fill density compliance.
- Production Supervisor: Oversees the capsule filling process, ensures that operators follow the SOP, and ensures that any issues are addressed promptly.
4. Accountability
The Capsule Manufacturing Supervisor is accountable for ensuring that fill density is monitored as per the SOP, and corrective actions are taken if necessary. The QA Manager is responsible for overseeing the overall compliance and ensuring the final product meets the required specifications.
5. Procedure
5.1 Monitoring Capsule-Fill Density
Monitor the fill density during capsule production to ensure that each capsule meets the specified requirements for content uniformity:
-
Prepare for Density Monitoring
- Ensure that the capsule filling machine is calibrated and functioning properly before starting production.
- Verify that the fill material is adequately mixed and that the granules or powder are uniform in size and consistency.
-
Select Sampling Method
- Randomly select a set number of capsules at different stages of the production run (e.g., every 30 minutes or after every 500 capsules). The selected samples should be representative of the entire batch.
- Document the time of sampling and batch number in the Sampling Log (Annexure-1).
-
Measure Capsule-Fill Density
- Weigh each capsule individually and record the data. Ensure the use of an analytical balance calibrated according to the prescribed standards.
- Calculate the fill density by dividing the weight of the capsule by the known volume of the capsule shell. Compare the result to the specification limits for the fill density.
- If using liquid-filled capsules, ensure that the liquid is evenly distributed and that there are no air bubbles present in the capsule before weighing.
-
Document Results
- Record the fill density for each capsule sampled, including the time, weight, and calculated density, in the Fill Density Log (Annexure-2).
- Ensure that all data entries are signed off by the responsible operator and reviewed by QC personnel.
5.2 Handling Deviations
If the capsule fill density does not meet the specified range, take the following corrective actions:
-
Investigate the Cause of Deviation
- Identify any factors that could have contributed to the deviation, such as equipment malfunction, variation in raw materials, or incorrect fill material preparation.
- Check the capsule filling machine for proper calibration, and ensure that there is no material build-up in the feeding system.
-
Correct the Process
- Adjust the machine settings, refill material preparation, or capsule handling as needed to correct the fill density deviation.
- If the issue cannot be resolved immediately, halt the production process and investigate further.
-
Re-sample and Re-test
- After adjustments are made, conduct a new set of random tests to ensure that the fill density is back within acceptable limits.
- Document all findings, including the cause of deviation and the actions taken, in the Deviation Log (Annexure-3).
5.3 Frequency of Monitoring
The frequency of monitoring depends on the production volume and batch size. It is recommended to monitor fill density at regular intervals:
- For small batches, conduct fill density monitoring at least once every 100 capsules.
- For large batches, conduct monitoring at least once every 500 capsules or every 30 minutes of production.
- Increase the frequency of checks if any inconsistencies are detected or if adjustments are made to the filling process.
5.4 Final Approval and Release
Once the monitoring process is completed and the fill density is verified to meet specifications, proceed with the following steps:
-
QA Review
- The QA team reviews all fill density records, including any deviations and corrective actions taken.
- Ensure that all data is complete and accurate, and that the batch complies with the fill density specifications.
-
Approval for Release
- If the capsule fill density is within the required range, approve the batch for continued production or packaging.
6. Abbreviations
- SOP: Standard Operating Procedure
- GMP: Good Manufacturing Practice
- QC: Quality Control
- QA: Quality Assurance
7. Documents
- Fill Density Log (Annexure-2)
- Sampling Log (Annexure-1)
- Deviation Log (Annexure-3)
- Batch Records (Annexure-4)
8. References
- USP <1163> – Pharmaceutical Dosage Forms: Capsules
- FDA Guidelines for Capsule Manufacturing
- Good Manufacturing Practice (GMP) Guidelines
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Sampling Log
| Sample ID | Sampling Time | Operator | Batch ID |
|---|---|---|---|
| Sample 001 | 10:00 AM | John Doe | Batch 001 |
Annexure-2: Fill Density Log
| Sample ID | Weight (mg) | Fill Density (g/cm³) | Pass/Fail | Operator |
|---|---|---|---|---|
| Sample 001 | 500 | 0.75 | Pass | Jane Smith |
Annexure-3: Deviation Log
| Deviation ID | Batch ID | Description | Corrective Action You said: continue ChatGPT said: Certainly! Continuing from Annexure-3: Deviation Log: html |
Corrective Action | Operator | Approval Status |
|---|---|---|---|---|---|---|
| DEV-001 | Batch 001 | Fill density outside acceptable range | Re-calibrated machine and adjusted material flow | John Doe | Approved |
Annexure-4: Batch Records
| Batch ID | Gelatin Composition | Fill Material | Operator | Adjustments Made | Approval Status |
|---|---|---|---|---|---|
| Batch 001 | Standard | Powdered Fill | Jane Smith | Adjusted for temperature variation in production environment | Approved |
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 monitoring frequency and adjustments | Improved accuracy and compliance | QA Head |