Novel Diagnostic Platforms for Clinical Microbiology and Sterility Testing for Cell Therapy

传统的微生物工作是缓慢的，有时不准确，依赖于表型培养鉴定，然后进行抗菌药物敏感性测试。基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）和实时分子检测（抗菌素耐药基因微阵列）等新技术提高了临床微生物实验室的诊断能力，并为研究和开发创造了一个令人兴奋的领域。鉴于这些平台产生的深入和高度准确（有时复杂）的结果，需要进行仔细的详细分析，以更好地了解所鉴定微生物的临床意义和检测到的耐药机制。 在本财政年度，我们<71>使用从cGMP环境中回收的118种微生物，对USP药典方法与自动化Bactec FX系统和BacTAlert Dual-T系统进行了大型比较评价，以评估检测细胞治疗产品中环境污染物的分析性能。这项研究是迄今为止同类研究中规模最大的一项，提供了强有力的数据，支持某些自动培养系统和设置的临床应用，如果辅以改进的真菌检测方法，作为USP药典方法的替代方法<71>。临床系统检测产品中环境污染物的局限性很重要，因为临床环境中对细胞治疗的需求不断扩大。

Traditional microbiological work up is slow and sometimes inaccurate, relying on phenotypic culture identification followed by antimicrobial susceptibility testing. Newer technologies, such as matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and real-time molecular detection (antimicrobial resistance genes microarrays) have advanced the diagnostic capabilities of clinical microbiology laboratories and have created an exciting field for research and development. Given the in-depth and highly accurate (sometimes complex) results that are produced by such platforms, careful detailed analyses are required to better understand the clinical significance of the organisms identified and the resistance mechanisms detected. During this fiscal year, we performed a large comparative evaluation of the compendial USP<71> method against the automated Bactec FX system and BacTAlert Dual-T system using 118 organisms recovered from cGMP environments to assess analytical performance for the detection of environmental contaminants in cell therapy products. This study is the largest of its kind to date, and provides strong data to support the clinical application of certain automated culture systems and settings, if supplemented with improved fungal detection methods, as an alternative method to the USP<71> compendial method. The limitations of clinical systems to detect environmental contaminants in products is important as the demand for cell therapy expands in the clinical setting.