Bacterial Retention Testing

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Challenge Each Membrane with “Worst-Case” Experiments

Bacterial Retention Testing ensures that when loaded with bacteria, the filter will produce a sterile effluent. It is a critical step in filter validation.

This study is required by all regulatory bodies worldwide. The United States Food and Drug Administration Guidance on Sterile Drug Products Produced by Aseptic Processing recommends that microbial retention testing be conducted using the pharmaceutical candidate preparation under simulated processing conditions; this validates performance of sterilizing-grade filter. European Union, Japan, and China Good Manufacturing Practices also refer to this test. The Parenteral Drug Association’s (PDA) Technical Report 26 further outlines parameters to be considered and modeled during the testing process. BioReliance® Validation Services testing is performed in compliance with these guidelines.

Testing is conducted using end-user worst-case processing conditions to determine the ability of a sterilizing-grade filter to retain a minimum challenge of 10⁷ bacteria per cm² of filter area.

Brevundimonas diminuta (B. diminuta) is commonly used as a challenge microorganism. With appropriate justification from bioburden characterization conducted by end-user, other strains could be used for the test.

Highly skilled Validation Specialists perform bacterial retention tests in a controlled laboratory using calibrated equipment and methods that are governed by a robust quality system:

• Every lab strictly adheres to Parenteral Drug Product (PDA) guidelines and American Society for Testing and Materials (ASTM) standards
• A robust and compliant challenge consists of one lot of finished drug product or process fluid to be evaluated using three lots of Merck sterilizing-grade, 47 mm membrane discs
• Includes at least one membrane at or near the minimum integrity specification
• Size controls prove that the test organism has the appropriate size
• Includes preliminary studies such as viability test to select the appropriate challenge solution and a recovery test to ensure that any possible bacteria can be recovered on the collection filters
• Simulation of process conditions with the drug product provides empirical evidence.