Standard Operating Procedure for Conducting Endotoxin Testing for Cream Products
| Department | Creams |
|---|---|
| SOP No. | SOP/CRM/156/2025 |
| Supersedes | SOP/CRM/156/2022 |
| Page No. | Page 1 of 6 |
| Issue Date | 21/01/2026 |
| Effective Date | 26/01/2026 |
| Review Date | 21/01/2027 |
1. Purpose
The purpose of this SOP is to define the procedure for conducting endotoxin testing on cream products. Endotoxin testing ensures that the cream formulations meet safety standards by verifying that endotoxin levels are within acceptable limits, preventing any potential risks to users.
2. Scope
This SOP applies to all cream products manufactured at the facility that require endotoxin testing. It covers the preparation, execution, and documentation of endotoxin testing using the Limulus Amebocyte Lysate (LAL) assay method.
3. Responsibilities
- Quality Control (QC) Team: Responsible for preparing the sample, performing endotoxin testing, recording results, and reporting any deviations from the acceptable limits.
- Quality Assurance (QA) Team: Responsible for reviewing endotoxin testing results, ensuring compliance with specifications, and taking corrective actions if required.
- Production Team: Responsible for providing accurate batch records and ensuring that the cream product meets the required quality standards before testing.
4. Accountability
The QC Manager is accountable for ensuring that endotoxin testing is conducted as per this SOP. The QA Manager is responsible for reviewing and approving testing results, ensuring compliance with internal and regulatory standards. The Production Supervisor is responsible for ensuring that all necessary batch records and samples are provided for testing.
5. Procedure
5.1 Pre-Test Preparation
- Ensure that all required materials for endotoxin testing are available, including the LAL reagent, standard endotoxin, test tubes, and sterile equipment.
- Review the batch record to ensure that the cream formulation meets the required specifications and that no issues were identified during production that could affect the endotoxin test.
- Prepare the sample by accurately weighing a known quantity of cream and dissolving it in an appropriate solvent (e.g., saline or buffer) according to the testing procedure.
- Ensure that all equipment used in the endotoxin testing process, such as pipettes and test tubes, are sterile and calibrated as required by the manufacturer’s guidelines.
5.2 Performing the LAL Assay
- Prepare the LAL reagent according to the manufacturer’s instructions. Ensure that the reagent is fresh and stored correctly.
- Add the LAL reagent to the sample solution in the required proportions as specified in the test procedure.
- Mix the solution thoroughly to ensure that the reagent is fully incorporated into the sample.
- Incubate the test tubes at the specified temperature for the recommended time period.
- After the incubation period, measure the turbidity or gel formation in the test tubes. Compare the results to the standard endotoxin values to determine the presence and quantity of endotoxins in the sample.
5.3 Data Interpretation
- If the turbidity or gel formation exceeds the established threshold value, the sample is considered to have failed the endotoxin test. If the test result is within the acceptable limits, the sample is considered acceptable.
- Record the results, including batch number, sample ID, test date, endotoxin levels, and the operator’s initials, in the Endotoxin Testing Log (Annexure-1).
- If the result is out of specification (OOS), follow the OOS investigation procedure to identify the root cause of the failure and document corrective actions.
5.4 Post-Test Activities
- Ensure that all used test materials and reagents are disposed of properly according to safety guidelines for hazardous waste.
- Perform any required post-test clean-up of equipment and work areas to ensure no cross-contamination occurs for future tests.
- Review the test results and submit them for review by the QA team for approval and documentation.
5.5 Documentation and Record-Keeping
- Ensure that all endotoxin testing results, including failure reports and corrective actions, are documented in the Endotoxin Testing Log (Annexure-1).
- Ensure that all related records, including batch production records and any deviation reports, are properly archived for future reference and audits.
- Retain records for a minimum of two years or as required by regulatory guidelines.
- Ensure that records are reviewed and approved by the Quality Assurance team to verify compliance with GMP standards and regulatory requirements.
6. Abbreviations
- GMP: Good Manufacturing Practices
- QC: Quality Control
- QA: Quality Assurance
- PPE: Personal Protective Equipment
- LAL: Limulus Amebocyte Lysate
- OOS: Out-of-Specification
7. Documents
- Annexure-1: Endotoxin Testing Log
8. References
- Good Manufacturing Practices (GMP) Guidelines – 21 CFR Part 211
- International Conference on Harmonisation (ICH) Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
- Pharmacopeial Monographs on Endotoxin 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: Endotoxin Testing Log
| Batch Number | Sample ID | Test Date | Endotoxin Level | Operator |
|---|---|---|---|---|
| 12345 | S-001 | 21/01/2026 | Pass | John Doe |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/03/2024 | 1.0 | Initial Version | New SOP Creation | QA Head |
| 01/03/2025 | 2.0 | Format Revision and Updates | Standardization of Document | QA Head |