Evaluation of an automated blood culture detection system for sterility testing of cellular and gene therapy products.

Sterility testing of cellular and gene therapy products is required to ensure safe infusion for the recipient. Sterility testing is often performed using broth-based media per the biopharmaceutical compendial USP <71> method. Automated blood culture systems have emerged as a potential alternative method, but data remain limited. It also remains unclear whether different cellular and gene therapy product formulations inhibit microbial growth during sterility testing, which could lead to false-negative sterility results. This study evaluated the ability to perform sterility testing using the BacT/Alert Virtuo automated blood culture system, BacT/Alert FA plus (aerobic) and FN plus (anaerobic) blood culture bottles, and two product formulations: (i) Plasmalyte-A + 2.5% human serum albumin (HSA) and (ii) Plasmalyte-A + 5% HSA + 5% dimethyl sulfoxide (DMSO). Contrived specimens were created using either formulation or a saline-only growth control inoculated with IMPORTANCE: Cellular and gene therapy products have emerged in recent years as an important treatment modality at large academic medical centers; however, these products must be tested for microbial contamination to ensure product safety. Compared to the gold standard, agar-based solid media method, automated blood culture systems have emerged as a potential alternative method of sterility testing. Here, we evaluated the ability of an automated blood culture detection system (BacT/Alert Virtuo) to reliably detect diverse microorganisms, ranging from bacteria to mold, in two standard cellular and gene therapy product formulations. Our results support current evidence that the use of automated blood culture detection systems is a reliable alternative method of sterility testing for different formulations of cellular and gene therapy products.