Standard Operating Procedure for Endotoxin Testing

1) Purpose

This SOP outlines the procedures for conducting endotoxin testing on pharmaceutical products to ensure they are free from endotoxins and safe for use, complying with regulatory standards.

2) Scope

This SOP applies to all batches of pharmaceutical products that require endotoxin testing, including raw materials, in-process samples, and finished products.

3) Responsibilities

The Microbiology department is responsible for conducting endotoxin testing. Quality Assurance (QA) is responsible for overseeing the process and ensuring compliance with this SOP and regulatory requirements.

4) Procedure

4.1 Preparation

1. Review the endotoxin testing protocol and ensure all necessary materials and equipment are available (e.g., Limulus Amebocyte Lysate (LAL) reagents, pyrogen-free glassware, incubator).
2. Verify the cleanliness and sterility of the testing environment and equipment.

4.2 Sample Collection

1. Collect samples aseptically according to the sampling plan. Ensure samples are representative of the batch and handled in a manner that prevents contamination.
2. Label the samples with all relevant information (e.g., product name, batch number, date of sampling).

4.3 Testing Method

1. Prepare the test sample and LAL reagent according to the endotoxin testing protocol.
2. Mix the test sample with LAL reagent in pyrogen-free tubes.
3. Incubate the mixture at the specified temperature and for the duration outlined in the protocol.
4. Observe and record the reaction, specifically looking for gel formation or turbidity, depending on the type of LAL test (e.g., gel-clot, turbidimetric, or chromogenic).

4.4 Data Analysis and Interpretation

1. For the gel-clot method, analyze the results based on the presence or absence of a gel clot after the incubation period.
2. For the turbidimetric or chromogenic methods, measure the optical density or color change, respectively, and compare the results to a standard curve.
3. Interpret the results against predefined acceptance criteria to determine if the product meets endotoxin limits.

4.5 Reporting and Documentation

1. Document all testing activities, observations, and results in the appropriate logbooks and records.
2. Prepare an endotoxin test report summarizing the findings, including any deviations or observations.
3. Review and approve the test report to ensure accuracy and compliance with regulatory requirements.

4.6 Corrective and Preventive Actions (CAPA)

1. Initiate CAPA procedures if test results indicate the presence of endotoxins or other issues.
2. Implement corrective actions to address the root cause of any contamination and prevent recurrence.

5) Abbreviations, if any

SOP: Standard Operating Procedure
QA: Quality Assurance
LAL: Limulus Amebocyte Lysate
CAPA: Corrective and Preventive Actions

6) Documents, if any

Endotoxin Testing Protocol, Sampling Records, Test Results Logbooks, Endotoxin Test Reports, CAPA Records

7) Reference, if any

Regulatory guidelines such as USP <85> Bacterial Endotoxins Test, European Pharmacopoeia (Ph. Eur.) 2.6.14 Bacterial Endotoxins, FDA Guidance for Industry: Pyrogen and Endotoxins Testing: Questions and Answers

8) SOP Version

Version 1.0