Standard Operating Procedure for Pyrogen Testing

1) Purpose

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

2) Scope

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

3) Responsibilities

The Microbiology department is responsible for conducting pyrogen 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 pyrogen testing protocol and ensure all necessary materials and equipment are available (e.g., pyrogen-free syringes, pyrogen-free glassware, reagents).
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. Rabbit Pyrogen Test:
   1. Prepare the test solution according to the pyrogen testing protocol.
   2. Inject the test solution into the marginal ear vein of rabbits.
   3. Monitor and record the rabbits’ body temperatures at specified intervals before and after injection.
2. LAL (Limulus Amebocyte Lysate) Test:
   1. Prepare the test sample and LAL reagent according to the pyrogen testing protocol.
   2. Mix the test sample with LAL reagent and incubate under specified conditions.
   3. Observe the reaction and interpret the results based on the presence or absence of gel formation.

4.4 Data Analysis and Interpretation

1. For the Rabbit Pyrogen Test, analyze the temperature data to determine if there is a significant increase indicating the presence of pyrogens.
2. For the LAL Test, interpret the results based on gel formation, comparing them against predefined acceptance criteria.

4.5 Reporting and Documentation

1. Document all testing activities, observations, and results in the appropriate logbooks and records.
2. Prepare a pyrogen 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 pyrogens 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

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

7) Reference, if any

Regulatory guidelines such as USP <151> Pyrogen Test, European Pharmacopoeia (Ph. Eur.) 2.6.8 Pyrogens, FDA Guidance for Industry: Pyrogen and Endotoxins Testing: Questions and Answers

8) SOP Version

Version 1.0