Regulatory Approval & Commercialization of an RBC Processing and Storage System to Improve Transfusion Therapy by Minimizing Oxidative Damage to RBC during Storage

 描述(由申请人提供)：该项目的目标是将Hemanext存储系统商业化，通过建立和维护一个用于冷藏红细胞存储的厌氧环境来提供质量显著提高的红细胞。更高质量的红细胞产品将表现出与传统制备的低剂量红细胞的生物等效性，因为更高的红细胞回收率，更好的微血管灌流和氧气输送，以及涉及不良事件的药物的减少。Hemanext存储系统的设计参考了对现有血库操作实践的详细研究，以最大限度地兼容现有程序、设备使用和成本。下文所述的第二阶段工作将以正在进行的第二阶段合同所取得的成果为基础。在第二阶段合同的支持下，设计和制造了第一代一次性氧气还原和厌氧存储系统，目的是进行所需的关键临床研究，以实现FDA的批准。这项二期桥方案的四个目标是：第一，在两种处理条件下，对6名受试者进行一项枢轴前双臂临床研究。第一代支持IDE的商用设备将在霍克斯沃斯血液中心进行测试，以验证Hemanext存储系统是否适合血液中心的预存储组件处理操作，并测量脱氧和厌氧存储对体内复苏和体外血液质量参数的影响。第二，进行关键的临床研究，以支持FDA监管机构提交的Hemanext存储系统。霍克斯沃斯血液中心和诺福克的美国红十字会中大西洋地区研究中心是计划中的关键临床研究地点。第三，在哥伦比亚大学进行体内恢复研究，展示建立和维持厌氧环境如何减轻辐射对红细胞的损害。第四，应用红细胞代谢组学、脂类组学、生物力学和血管生物活性的系统生物学分析，寻找可预测体内恢复的新生物标志物。如果需要，所有研究都将在符合FDA标准的IRB的授权下进行。

 DESCRIPTION (provided by applicant): The objective of this project is to commercialize the Hemanext Storage System to deliver red blood cells (RBC) of significantly improved quality by establishing and maintaining an anaerobic environment for refrigerated RBC storage. The higher quality red blood cell product will exhibit bioequivalence vs. conventionally prepared RBC with lower doses by virtue of higher RBC recovery, superior microvascular perfusion and oxygen delivery and a reduction in agents implicated in adverse events. The design of the Hemanext Storage System has been informed by detailed study of existing blood bank operating practices to maximize compatibility with existing procedures, equipment use, and cost. The Phase IIB work described below will build on the outcomes achieved in an ongoing Phase II contract. Supported by the Phase II contract, a first generation disposable oxygen reduction and anaerobic storage system was designed and fabricated with the objective of performing the required pivotal clinical studies to achieve FDA clearance. The four aims of this Phase II Bridge proposal are: First, to conduct a pre-pivotal, dual-arm clinical study with 6 subjects under 2 processing conditions. A first generation, IDE-ready commercial device will be tested at Hoxworth Blood Center to both verify the fit of the Hemanext Storage System into pre-storage component processing operations at a blood center and to measure the impact deoxygenation and anaerobic storage have on in vivo recovery and in vitro blood quality parameters. Second, to conduct the pivotal clinical study to support the FDA regulatory submission of the Hemanext Storage System. Hoxworth Blood Center and the American Red Cross Mid-Atlantic Region Research Center in Norfolk are the planned pivotal clinical study sites. Third, to conduct an in vivo recovery study at Columbia University to demonstrate how establishing and maintaining an anaerobic environment mitigates the damage done to red blood cells by irradiation. Fourth, to apply systems biology analytics of red blood cell metabolomics, lipidomics, biomechanics, and vascular bioactivity to identify novel biomarkers that are predictive of in vivo recovery. All studies will be performed, where required, under the authorization of an FDA-compliant IRB.