Comparing Safety Margin Methods for USP <72> Compliance

Automated growth-based methods are often used for rapid microbial contamination detection in short shelf-life pharmaceutical products such as Cell and Gene Therapies (CGT). For such products, every hour gained on release testing is vital to patients in need.

The BACT/ ALERT® 3D (BTA) Solution is an automated, non-destructive, growthbased, rapid microbial method, capable of detecting a variety of aerobic and anaerobic microorganisms including fungi, utilizing a combination of culture bottles and incubation temperatures. Although most relevant microorganisms are detected in less than 72 hours, the most common practice is the release of product after 7 days incubation.

The introduction of USP <72> now gives manufacturers the opportunity to release products in less than 7 days, by providing guidance on the determination of the required incubation time. This determination considers the slowest-growing microorganism plus a safety margin.

Using the most common microorganisms encountered in CGT, we compare different methods assessing applicability, repeatability, and robustness of:

• traditional plate enumeration, 
• optical density, 
• and a novel approach using the kinetics of the BACT/ALERT® system (TTD method).