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Fast-Track Safety: The Science Behind Rapid Microbial Testing


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The USP Chapter 1071 provides guidance on rapid microbial tests for products with a short shelf-life or those prepared for immediate use. These products include compounded sterile preparations (CSPs), positron emission tomographic (PET) products, and cell and gene therapies. Traditional growth-based sterility tests with a 14-day incubation period are not suitable for such products due to their rapid administration to patients before test completion.

Recommended Rapid Technologies: USP 1071 outlines several recommended rapid technologies:


  • Adenosine Triphosphate (ATP) Bioluminescence: Measures ATP levels as an indicator of microbial presence.

  • Flow Cytometry: Analyzes individual cells based on size, granularity, and fluorescence.

  • Isothermal Microcalorimetry: Monitors heat production during microbial metabolism.

  • Nucleic Acid Amplification: Detects specific microbial DNA or RNA.

  • Respiration: Measures microbial oxygen consumption.

  • Solid Phase Cytometry: Identifies microbial cells using antibodies and fluorescence.


Validation Considerations: When planning to validate a rapid method as a replacement for traditional sterility tests, consider:


  • User Requirements: Ensure the rapid test meets user needs.

  • Validation Criteria: Define acceptance criteria for the rapid method.

  • Comparative Studies: Conduct side-by-side studies with traditional methods.

  • Specificity: Assess the method’s ability to detect relevant microorganisms.

  • Limit of Detection (LOD): Determine the lowest microbial concentration detectable.

  • Sample Size: Optimize sample size for reliable results.

  • Patient Safety: Prioritize patient well-being during validation.


Rapid microbial tests offer a risk-based approach for releasing sterile short-life products, addressing the limitations of traditional methods. These advancements enhance patient safety and streamline product release processes.


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