Standard Operating Procedure for Endotoxin Testing in Aseptic Aerosols
1) Purpose
The purpose of this SOP is to establish procedures for conducting endotoxin testing on aseptic aerosol products to ensure the absence of endotoxins, which are critical for product safety.
2) Scope
This SOP applies to endotoxin testing performed on aseptic aerosol products manufactured by [Company Name] to ensure compliance with regulatory standards and product safety.
3) Responsibilities
Microbiology Laboratory: Perform endotoxin testing according to approved protocols and regulatory guidelines.
Quality Control (QC) Team: Provide aerosol samples for testing and coordinate sample collection.
Regulatory Affairs: Review and approve endotoxin testing protocols to ensure compliance with regulatory guidelines.
Quality Assurance (QA) Team: Oversee adherence to SOPs and ensure documentation accuracy and completeness.
4) Procedure
4.1 Sample Collection and Preparation:
4.1.1 Collect representative samples of aseptic aerosol products from the final production batch under aseptic conditions.
4.1.2 Ensure samples are properly labeled and identified to maintain traceability.
4.1.3 Store samples under appropriate conditions (e.g., refrigerated) prior to testing to preserve sample integrity.
4.2 Test Setup and Reagents Preparation:
4.2.1 Prepare reagents and solutions required for endotoxin testing, following compendial guidelines (e.g., Limulus Amebocyte Lysate – LAL reagent).
4.2.2 Ensure all reagents and solutions are sterile
4.2.3 Calibrate the LAL testing system or equipment according to the manufacturer’s instructions.
4.3 Endotoxin Testing Procedure:
4.3.1 Inoculate sample wells with prepared aerosol samples, ensuring accurate volume and proper dispersion.
4.3.2 Add LAL reagent to each well, following the manufacturer’s protocol, and mix thoroughly.
4.3.3 Incubate the sample wells at the specified temperature (e.g., 37°C) for the required duration (e.g., 60 minutes) to allow endotoxin reaction.
4.4 Detection and Reading:
4.4.1 Observe the sample wells for color change or turbidity, indicating the presence of endotoxins.
4.4.2 Use a photometer or LAL reader to quantify endotoxin levels in the samples, following the instrument’s calibration and procedure.
4.4.3 Record and document all test results, including absorbance values and endotoxin concentration.
4.5 Controls and Validation:
4.5.1 Include appropriate positive and negative controls in each endotoxin test to validate test procedures and reagents.
4.5.2 Ensure controls meet acceptance criteria before interpreting sample results.
4.5.3 Perform validation of endotoxin testing methods and procedures according to regulatory requirements.
4.6 Result Interpretation:
4.6.1 Evaluate test results after the specified incubation period to determine the presence or absence of endotoxins.
4.6.2 Compare test results against predefined acceptance criteria for endotoxin levels.
4.6.3 Document all test results, including raw data, observations, and interpretations.
4.7 Reporting and Documentation:
4.7.1 Prepare detailed endotoxin test reports summarizing testing methods, results, and conclusions.
4.7.2 Review and approve test reports by designated personnel to ensure accuracy and compliance with SOPs.
4.7.3 Maintain records of all endotoxin testing activities, including sample preparation, reagent preparation, testing, and approval documentation.
4.8 Non-Conformance Handling:
4.8.1 Initiate non-conformance reports (NCRs) for aseptic aerosol products that fail endotoxin testing or exceed acceptance criteria.
4.8.2 Investigate root causes of non-conformance and implement corrective actions to prevent recurrence.
4.8.3 Verify effectiveness of corrective actions through retesting and document outcomes accordingly.
5) Abbreviations, if any
SOP: Standard Operating Procedure
QC: Quality Control
QA: Quality Assurance
NCR: Non-Conformance Report
LAL: Limulus Amebocyte Lysate
6) Documents, if any
Endotoxin Testing Protocol
Endotoxin Test Reports
Reagent Preparation Records
Calibration Records for LAL Testing Equipment
Validation Reports for Endotoxin Testing Methods
Non-Conformance Reports (NCRs)
Approval Records and Documentation
7) Reference, if any
USP Chapter Endotoxin Testing – General Information
EP Chapter Endotoxin Testing – Microbial Enumeration Tests
ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
8) SOP Version
Version 1.0