Rapid, Near-Tranfusion Test for Bacteria in Platelets Units

描述(申请人提供)：血小板的细菌污染被认为是目前输血产品最大的感染风险，约为2000个血小板单位中的1个，比艾滋病毒高出几个数量级。高水平的细菌污染可导致输血接受者的严重发病率或死亡率。美国血库协会在2004年和2011年发布了指令，要求对所有血小板单位进行细菌测试。最近的两项研究表明，目前FDA批准的基于培养的方法在输血前1至4天检测污染，漏掉了大多数受污染的单位。采样和实际输血之间经过的时间以及相关的细菌污染风险是当前基于培养的血小板检测无法解决的一个根本问题。一种快速和灵敏的细菌污染问题点检测将通过在输血前立即提供潜在污染的评估来克服这一问题。这样的测试将被靠近输血点的医院实验室或准备将血小板单位运往临床中心的输血中心使用。理想情况下，快速检测需要不到15分钟，检测灵敏度为104cfu/mL或更高，完全自动化，成本与目前的检测相当。免疫公司开发的BacTx技术用于检测血小板中的细菌污染，该技术采用了一种独特的创新的分析化学，能够快速检测血小板单位中的革兰氏阳性和革兰氏阴性细菌。第一代BacTx细菌检测试剂盒最近获得了FDA(CBER)的批准，作为一种用于混合的、白细胞减少的全血衍生血小板的质量控制测试，但由于其长度(45分钟)和复杂性(需要离心和精确移液)，该测试不适合用作问题点测试。在第一阶段项目中，我们成功地证明了一种简单、基于过滤器的BacTx检测的可行性，该方法快速(15分钟)且高度自动化，同时保持了原始BacTx检测的高灵敏度和特异性。在第二阶段，我们将为自动化性能优化和配置快速测试，并将设计、建造和评估运行测试的原型仪器和软件。仪器和软件开发将与在开发具有类似功能的医疗测试系统方面拥有多年经验的工程合作伙伴合作进行。在第二阶段结束时，我们将开发和验证一个集成的快速BacTx测试系统，为510(K)批准的临床研究做好准备。这种快速检测的商业化将使血小板检测的模式发生转变，并显著减少输入危重患者的受细菌污染的血小板单位的数量。此外，采用快速BacTx检测可能最终导致有关血小板的政策发生变化，允许将血小板单位的储存寿命从5天延长到7天，从而显著降低血库的成本。

DESCRIPTION (provided by applicant): Bacterial contamination of platelets is considered the greatest infectious risk of blood product transfusion today at about 1 in 2000 platelet units, which is several orders of magnitude greater than that of HIV. Bacterial contamination at high levels can lead to severe morbidity or mortality in transfusion recipients. The American Association of Blood Banks issued directives in 2004 and 2011 requiring bacterial testing on all platelet units. Two recent studies have demonstrated that current FDA-approved culture-based methods that test for contamination 1 to 4 days prior to transfusion miss a majority of contaminated units. The time elapsed between sampling and actual transfusion and the associated risk of bacterial contamination is a fundamental problem that cannot be addressed by current culture-based platelet testing. A rapid and sensitive point-of-issue test for bacterial contamination would overcome this problem by providing an assessment of potential contamination immediately prior to transfusion. Such a test would be used by a hospital laboratory close to the point of transfusion or by a transfusion center preparing to ship platelet units to a clinical center. A rapid test would ideally require less than 15 min, have detection sensitivity of 104 CFU/mL or better, be fully automated, and be comparable in cost to current tests. BacTx technology, developed by Immunetics for detection of bacterial contamination in platelets, employs a unique and innovative assay chemistry capable of rapidly detecting both Gram-positive and Gram-negative bacteria in platelet units. The first-generation BacTx Bacterial Detection Kit recently received clearance from FDA (CBER) as a quality control test for pooled, leukocyte-reduced whole blood derived platelets, but this test is not ideally suited for use as a point of issue test due to its length (45 min) and complexity (requiring centrifugation and accurate pipetting). In the Phase I project, we successfully demonstrated feasibility of a simple, filter-based BacTx assay which is rapid (<15 min) and highly amenable to automation, while maintaining the high sensitivity and specificity of the original BacTx test. In Phase II, we will optimize and configure the rapid test for automated performance and will design, build and evaluate prototype instruments and software to run the test. The instrument and software development will be carried out in collaboration with engineering partners who have many years of experience in the development of medical test systems with comparable functionality. At the conclusion of Phase II, we will have developed and validated an integrated rapid BacTx test system ready for clinical studies aimed at 510(k) approval. Commercialization of this rapid test will enable a paradigm shift in platelet testing and a significant reduction in the number of bacterially contaminated platelet units transfused into critically ill patients. Furthermore, adopton of the rapid BacTx test could ultimately lead to a change in policy regarding platelets, significantly reducing costs for blood banks by allowing an extension of the storage life of platelet units from 5 to 7 days.