Accelerating sterility testing: Symcel calScreener+ achieves results in <3 days with direct inoculation in non-destructive and continuous monitoring system

Background & Aim

Sterility testing is a critical quality control process for cell and gene therapy products (CGTPs), where rapid and reliable detection of microbial contaminants is essential to meet regulatory standards and ensure patient safety. Traditional sterility testing methods, requiring up to 14 days, delay batch release and increase costs. The Symcel calScreener+ utilizes isothermal microcalorimetry to enable faster, phenotypic detection of microbial contaminants in a non-destructive and product-matrix-independent manner. This study evaluates the calScreener+ 3-day sterility test for its accuracy, reliability, detection times, and robustness in addressing challenges such as small sample volumes and complex matrices with high eukaryotic cell concentrations.

Methodology

The calScreener+ monitors metabolic activity in product samples as low as 0.05 ml to detect microbial growth. Validation studies assessed its Limit of Detection (LOD), detection times, comparability, and specificity range across 20 microbial strains relevant to regulatory guidelines. The evaluation used TSB and FTM media at dual temperatures (25°C and 35°C) and included key microorganisms such as Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Aspergillus brasiliensis, and Cutibacterium acnes. Robustness and ruggedness were assessed under varying conditions, including temperature fluctuations and growth inhibitors. Statistical analyses confirmed reliability and reproducibility.

Results

The calScreener+ demonstrated an LOD of <5 CFU and delivered results within 3 days, even in complex matrices with high eukaryotic cell concentrations (10^6–10^8 cells/ml). Detection times included S. aureus, P. aeruginosa, and C. albicans within 24 hours; A. brasiliensis within 30 hours; and C. acnes within 60 hours. It effectively detected a broad range of microorganisms relevant to sterility testing, including critical contaminants such as Burkholderia complex and Penicillium species, with robust performance under varying conditions.

Conclusion

The Symcel calScreener+ offers a sensitive and rapid solution for sterility testing in CGTPs, enabling phenotypic detection of microbial contaminants within days instead of weeks. Its small sample volume minimizes material use, ideal for limited batch sizes. By eliminating enrichment steps and reducing detection times, the calScreener+ streamlines workflows and enhances operational efficiency, positioning it as a transformative tool for pharmaceutical quality control.