Standard Operating Procedure for Related Substance Testing for Extended Release Tablets
| Department | Tablet |
|---|---|
| SOP No. | SOP/TAB/083/2025 |
| Supersedes | SOP/TAB/083/2022 |
| 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 testing related substances in extended release tablets, ensuring that the content of related substances in the tablets is within the specified limits, thereby ensuring product quality and compliance with regulatory standards.
2. Scope
This SOP applies to the related substance testing of extended release tablets to evaluate impurities and degradation products in accordance with pharmacopeial guidelines and internal specifications.
3. Responsibilities
- Manufacturing Personnel: Responsible for providing the sample of extended release tablets for testing and ensuring that they are free from visible defects.
- Quality Control (QC): Responsible for conducting the related substance testing, recording the results, and ensuring compliance with established limits for impurities.
- Quality Assurance (QA): Ensures that the testing procedure is followed correctly and reviews the results for batch approval and regulatory compliance.
4. Accountability
The QC Manager is accountable for ensuring that related substance testing is performed in compliance with this SOP and for reporting the
results. The QA Manager is responsible for reviewing the results and approving the batch for release.
5. Procedure
5.1 Sample Collection
- Collect a representative sample of extended release tablets from the batch, as specified in the batch record.
- The sample should consist of 6 tablets (or as specified in the batch record or pharmacopeial guidelines).
- Ensure that the tablets are free from defects such as cracks, chips, or contamination.
- Label the sample appropriately for identification during testing.
5.2 Preparation of Testing Apparatus
- Ensure that the analytical equipment (e.g., HPLC or GC system) is calibrated and properly maintained according to the manufacturer’s instructions and company’s equipment maintenance SOP.
- Prepare the mobile phase, standards, and sample solutions in compliance with the pharmacopeial methods or validated methods as specified in the batch record.
5.3 Performing the Related Substance Test
- Weigh the appropriate amount of sample from the extended release tablets and prepare the sample solution according to the method outlined in the batch record or pharmacopeial guidelines.
- Inject the sample solution into the chromatograph (HPLC or GC) and run the analysis according to the specified conditions (e.g., column type, flow rate, detection wavelength, and temperature).
- Simultaneously run the standard solution under the same conditions for comparison of impurity peaks.
5.4 Data Recording and Calculation
- Record the results, including the retention time, peak area, and relative retention times of any related substances in the sample solution.
- Calculate the percentage of related substances using the area or height of the related substance peaks and compare the results to the total content of the active pharmaceutical ingredient (API).
- Ensure that the total content of related substances is within the acceptable limits as specified in the batch record, typically ≤ 0.5% for individual impurities and ≤ 1.0% for total impurities, but this may vary depending on the product specifications.
5.5 Acceptance Criteria
- Ensure that the related substances do not exceed the limits specified in the pharmacopeia or batch record.
- If any impurity exceeds the specified limits, the batch should be investigated, and corrective actions should be documented in the deviation report (Annexure-2).
5.6 Documentation and Record-Keeping
- Document all related substance testing results, including chromatographic data and impurity calculations, in the batch record (Annexure-1).
- Record any deviations from the acceptance criteria in the deviation report (Annexure-2), along with the corrective actions taken.
- Ensure all records are signed, dated, and stored according to the company’s record retention policy for future audits and inspections.
5.7 Post-Test Cleanup
- Clean the analytical equipment (e.g., HPLC or GC system) according to the manufacturer’s instructions and the company’s cleaning SOP to avoid cross-contamination between tests.
- Ensure that all equipment is properly stored and maintained in good working condition for future use.
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
- GC: Gas Chromatography
7. Documents
- Batch Record (Annexure-1)
- Deviation Report (Annexure-2)
8. References
- USP <1085> – Impurities in Drug Substances
- 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
- European Pharmacopoeia (EP) – Testing for Related Substances
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 | Tablet Sample | Impurity Type | Impurity % | Result |
|---|---|---|---|---|
| Batch 001 | 6 tablets | Impurity A | 0.2% | Pass |
Annexure-2: Deviation Report
| Deviation Date | Batch Number | Deviation Description | Corrective Action | Responsible Person |
|---|---|---|---|---|
| 15/12/2025 | Batch 001 | Impurity level exceeded specification | Adjusted formulation process | John Doe |
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 Testing Parameters and Methods | Refined test methodology and impurity specifications | QA Head |