Comprehensive Evaluation of Compendial USP71, BacT/Alert Dual-T, and Bactec FX for Detection of Product Sterility Testing Contaminants

摘要

The emergence of cell therapy programs in large academic centers has led to an increasing demand for clinical laboratories to assist with product sterility testing. Automated blood culture systems have shown promise as alternatives to the manual USP71 compendial method, but current published data are limited by small organism test sets, particularly for molds. In 2015, failure of the Bactec FX system to detect mold contamination in two products prompted us to evaluate three test systems (compendial USP71, Bactec FX, and BacT/Alert Dual-T) over seven different culture combinations, using 118 challenge organisms representative of the NIH current good manufacturing practice (cGMP) environment. At 96 h and 144 h for bacterial and fungal detection, respectively, the compendial USP71 method significantly outperformed the Bactec FX system (84.7 versus 64.4; P = 0.0006) but not the BacT/Alert system at 32.5 degrees C (78.8; P = 0.3116). Extended incubation to 360 h with terminal visual inspection improved sensitivity, without a significant difference between compendial USP71 and BacT/Alert testing (95.7 versus 89.0; P = 0.0860); both systems were better than the Bactec FX system (71.2; P 0.0001 and P = 0.0003, respectively). The Bactec FX and BacT/Alert systems performed equivalently for 30 isolates derived from clinical bloodstream infections, confirming system optimization for clinical organisms rather than environmental contaminants. Paired Sabouraud dextrose agar (SDA) plates were always positive for fungi within the acceptable time frame. This study shows that the Bactec FX system is suboptimal for product sterility testing, and it provides strong data to support the use of BacT/Alert testing at 32.5 degrees C paired with a supplemental SDA plate as an acceptable alternative to the compendial USP71 method for product sterility testing.