Standard Operating Procedure for Residual Solvent Testing in Film-Coated Tablets
| Department | Tablet |
|---|---|
| SOP No. | SOP/TAB/084/2025 |
| Supersedes | SOP/TAB/084/2022 |
| Page No. | Page 1 of 6 |
| Issue Date | 01/03/2026 |
| Effective Date | 06/03/2026 |
| Review Date | 01/03/2027 |
1. Purpose
To outline the procedure for residual solvent testing in film-coated tablets, ensuring that the levels of residual solvents do not exceed the limits set by regulatory standards and internal specifications, ensuring product safety and compliance.
2. Scope
This SOP applies to the residual solvent testing of film-coated tablets to verify that the solvents used during the coating process have been adequately removed, and the tablets are within the acceptable limits for residual solvent content.
3. Responsibilities
- Manufacturing Personnel: Responsible for providing the sample of film-coated tablets for testing and ensuring the batch follows the required process parameters.
- Quality Control (QC): Responsible for conducting the residual solvent tests, recording the results, and ensuring that the levels are within the acceptable limits.
- Quality Assurance (QA): Ensures that the testing procedure is followed and reviews the results for batch approval and regulatory compliance.
4. Accountability
The QC Manager is accountable for ensuring that residual solvent 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 film-coated 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
- Prepare the testing apparatus, including a gas chromatograph (GC) or another suitable analytical instrument, according to the manufacturer’s instructions and company procedures.
- Prepare the calibration standards and solvent solutions as per the pharmacopeial guidelines or validated methods, ensuring they are free from contaminants.
5.3 Performing the Residual Solvent Test
- Weigh the appropriate amount of sample tablets and prepare the sample solution using an appropriate solvent or extraction method.
- Inject the sample solution into the GC or suitable analytical instrument to quantify the residual solvents present in the tablets.
- Simultaneously run a calibration standard to ensure accuracy of the results and compare the peaks from the sample against the standard solvent concentrations.
5.4 Data Recording and Calculation
- Record the results from the GC or analytical system, including the retention times and peak areas of the solvents detected.
- Calculate the concentration of residual solvents based on the peak areas and compare them with the specified limits for each solvent.
- Ensure that the residual solvent levels do not exceed the acceptable limits as specified in the pharmacopeia or batch record (e.g., ≤ 0.5% for commonly used solvents like ethanol, acetone, etc.).
5.5 Residual Solvent Acceptance Criteria
- Ensure that the levels of each residual solvent do not exceed the limits specified by regulatory authorities (such as USP, EP) or the product’s specifications.
- If any solvent exceeds the 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 the residual solvent test results, including solvent concentrations and the method used, in the batch record (Annexure-1).
- Record any deviations from the residual solvent specifications in the deviation report (Annexure-2), along with the corrective actions taken.
- Ensure that 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 testing apparatus, including the GC or other instruments used for analysis, according to the manufacturer’s instructions and the company’s cleaning SOP.
- 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
- GC: Gas Chromatography
- API: Active Pharmaceutical Ingredient
7. Documents
- Batch Record (Annexure-1)
- Deviation Report (Annexure-2)
8. References
- USP <467> – Residual Solvents
- 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
- European Pharmacopoeia (EP) – Testing for Residual Solvents
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 | Residual Solvent Type | Residual Solvent Level (%) | Result |
|---|---|---|---|---|
| Batch 001 | 6 tablets | Acetone | 0.2% | Pass |
Annexure-2: Deviation Report
| Deviation Date | Batch Number | Deviation Description | Corrective Action | Responsible Person |
|---|---|---|---|---|
| 12/11/2025 | Batch 001 | Residual solvent level exceeded specification | Adjusted drying process and retested | 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 | Improved residual solvent analysis method | QA Head |