Standard Operating Procedure for Uniformity of Content Testing for Capsules
| Department | Capsule Manufacturing |
|---|---|
| SOP No. | SOP/CM/183/2025 |
| Supersedes | SOP/CM/183/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 01/02/2025 |
| Effective Date | 05/02/2025 |
| Review Date | 01/02/2026 |
1. Purpose
The purpose of this SOP is to define the procedure for testing the uniformity of content in capsules. Uniformity of content ensures that each capsule contains the correct amount of active pharmaceutical ingredient (API), which is crucial for product efficacy, safety, and regulatory compliance. This SOP provides guidelines for performing uniformity of content testing to ensure consistency in every capsule produced.
2. Scope
This SOP applies to the testing of content uniformity for capsules. It covers the sampling, testing methods, and criteria for determining whether the capsules meet the required uniformity standards for API content. The SOP is applicable to all capsules, including hard and soft gelatin capsules, throughout the manufacturing process.
3. Responsibilities
- Quality Control (QC) Team: Responsible for performing the uniformity of content testing, including sample collection, testing, and documentation. QC also ensures that test results are within the predefined limits and investigates any deviations.
- Quality Assurance (QA) Team: Responsible for reviewing and approving the uniformity of content test criteria, methods, and ensuring that the process complies with GMP and regulatory standards. QA also handles the review of any deviations from the standards.
- Production Team: Responsible for ensuring that the appropriate number of capsules is sampled for content uniformity testing and that corrective actions are taken if deviations occur.
- Supervisory Personnel: Responsible for ensuring that the proper procedures are followed and that personnel performing the testing are trained appropriately.
4. Accountability
The QA Manager is accountable for ensuring the uniformity of content testing procedure is compliant with all regulatory requirements. The QC Supervisor is responsible for conducting the tests and ensuring that the sample collection and testing are carried out accurately. The Production Supervisor ensures that the sampling for testing is conducted at the correct stage of production and that necessary corrective actions are implemented.
5. Procedure
5.1 Pre-Testing Setup
Before performing uniformity of content testing, ensure the following steps are completed:
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Review Testing Criteria
- Review the uniformity of content acceptance criteria, ensuring they comply with the regulatory requirements (e.g., USP, EP). The acceptance criteria should be approved by the QA department before testing.
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Prepare Testing Area
- Ensure that the testing area is clean, organized, and equipped with calibrated analytical equipment such as a balance, dissolution apparatus, or HPLC system, depending on the method used for content testing.
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Calibrate Testing Equipment
- Ensure all testing equipment is calibrated according to the manufacturer’s instructions and documented in the Equipment Calibration Log (Annexure 1).
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Prepare Sampling Plan
- Define the number of capsules to be sampled. Typically, a sample size of 10-30 capsules is chosen, depending on the batch size and regulatory requirements. The sampling should be random and representative of the entire batch.
5.2 Uniformity of Content Testing Procedure
Follow these steps to perform uniformity of content testing:
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Sample Capsule Selection
- Randomly select the required number of capsules (typically 10 or more) from the batch. Ensure that the samples are representative of the entire batch.
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Test Capsule Content
- Open each selected capsule and remove the fill material. Weigh the fill material, if necessary, and dissolve it in a suitable solvent. For tablets, you may also use direct analysis or high-performance liquid chromatography (HPLC) to determine the content of the active pharmaceutical ingredient (API).
-
Calculate Content Uniformity
- Calculate the content of each capsule sample as a percentage of the label claim (i.e., the nominal dosage of the API). Compare the individual capsule content with the specified limits. The content of any individual capsule must not deviate by more than ±10% from the nominal dosage.
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Uniformity Criteria
- For 10 capsules sampled, not more than 2 capsules may deviate by more than ±10% from the label claim, and no capsule may deviate by more than ±15% from the label claim. If these limits are exceeded, the batch should be considered out of specification.
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Document Test Results
- Document the test results in the Uniformity of Content Testing Log (Annexure 2), including capsule ID, the weight or content of each capsule, and the percentage variation from the nominal dose. Record any deviations and the corrective actions taken.
5.3 Post-Testing Activities
After the uniformity of content testing is complete, ensure the following actions are taken:
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Review Test Results
- The QA Manager reviews the results to confirm that they comply with the uniformity of content criteria. If any capsules fail the test, initiate a root cause investigation and corrective action.
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Corrective Actions
- If the results indicate significant deviations, the production team must investigate potential causes such as formulation issues, equipment malfunctions, or raw material quality problems, and implement corrective actions.
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Training and Feedback
- Provide feedback to operators and re-train them if necessary to ensure proper sampling and testing procedures are followed.
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Record Keeping
- Ensure that all documentation related to content uniformity testing, including test results, batch details, and corrective actions, are archived in accordance with regulatory and company requirements.
6. Abbreviations
- SOP: Standard Operating Procedure
- GMP: Good Manufacturing Practice
- QA: Quality Assurance
- QC: Quality Control
- API: Active Pharmaceutical Ingredient
- HPLC: High-Performance Liquid Chromatography
7. Documents
- Annexure 1: Equipment Calibration Log
- Annexure 2: Uniformity of Content Testing Log
- Annexure 3: Deviation and Corrective Action Report
8. References
- FDA Guidance on Uniformity of Content Testing
- Good Manufacturing Practice (GMP) Guidelines
- USP <905> – Uniformity of Dosage Units
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure 1: Equipment Calibration Log
| Equipment ID | Calibration Date | Operator | Calibration Details | Next Calibration Due |
|---|---|---|---|---|
| Analytical Balance 401 | 01/02/2025 | John Doe | Calibration of precision and balance scale | 01/02/2026 |
Annexure 2: Uniformity of Content Testing Log
| Batch ID | Test Date | Capsule ID | API Content (mg) | Label Claim (mg) | Deviation (%) | Remarks |
|---|---|---|---|---|---|---|
| Batch 001 | 02/02/2025 | Capsule 001 | 500 | 500 | 0% | Pass |
Annexure 3: Deviation and Corrective Action Report
| Batch ID | Deviation Type | Corrective Action | Responsible Person | Completion Date |
|---|---|---|---|---|
| Batch 001 | Content Deviation | Adjust formulation | Production Supervisor | 03/02/2025 |
12. Revision History
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial version of SOP | Creation of SOP for uniformity of content testing | QA Head |
| 01/02/2025 | 2.0 | Updated test procedure and documentation format | Improved testing methodology and record-keeping | QA Head |