Portable Gas Perfusion System for Pancreas Preservation

描述(由申请人提供)：胰岛移植(ITX)是一种新兴的治疗标准胰岛素治疗不足的1型糖尿病患者的方法。I是胰腺移植的一种有前景的替代方案，因为ITX的手术风险和毒性较低。通过拟议的技术加强器官保存有可能增加挽救生命的ITX的数量，同时改善结果。在北美(大部分在加拿大)，在340名接受者中进行了840次输液，在欧洲，在775名接受者中进行了1380次输液。ITX是加拿大、英国和一些欧洲国家批准的护理标准。在美国，胰岛中心正准备根据北美临床试验的有利结果向FDA申请生物制品许可证；一旦获得批准，预计美国ITX的数量将大幅增加。吉纳便携式胰腺保存系统(P3S)将是第一个利用充气器官保存技术的完整、便携式商业系统。这项正在申请专利的技术通过电化学产生氧气。该系统通过气体灌流(充气)提供氧气，其中含有氧气的湿气通过冷藏器官的血管系统流动，以最大限度地减少缺氧时间。充气可以加强对胰腺和其他器官的保护。在I/II阶段计划中，经过开发和制造，8个便携式充气装置已在7个设施的临床前和临床使用。这些装置已用于55个以上的程序和1000多个小时的操作，包括在7次飞机飞行中。P3已被批准在加拿大航空公司的常规使用。在24小时保存的临床前测试中，与目前最先进的保存10小时的方法相比，人胰岛的产量高出76%(p&lt；0.003)；这种更高的产量将：(1)理论上，目前的itx接受者100%是 (2)将可移植胰岛制剂的比例从42%提高到81%。也有证据表明，基于胰岛素分泌分析的胰岛质量有所提高。加拿大埃德蒙顿阿尔伯塔大学的一项临床试验于2013年10月开始使用P3。在试点试验中，前四个胰腺充满的人中有四个(100%)导致 可移植的胰岛制剂与其42%的可移植制剂的历史标准进行了比较；而且，与历史对照相比，移植当天的存活率(以OCR/DNA衡量)显著增加。三种移植制剂中的两种已使患者在移植后2个月内实现了胰岛素独立。这些早期结果非常令人鼓舞，并证实了我们的临床前第二阶段结果。第二阶段B计划的目标是将该技术推向临床实施。在PhIIB结束时，我们预计将有一种医疗设备准备就绪：1)申请美国和美国临床研究使用的510K许可；2)在加拿大、欧洲和澳大利亚进行商业销售，并获得CE标志。PhIIB有3个目标：1)设计和生产12个符合国际医疗设备标准的试验性设备；2)临床前测试，评估研究级人类胰腺的胰岛；3)支持与加拿大ITX的临床测试(研究已获批准和启动试点研究)。

DESCRIPTION (provided by applicant): Pancreatic islet transplantation (ITx) is an emerging treatment for a subset of Type 1 diabetics for which standard insulin therapies are insufficient. I is a promising alternative to pancreas transplantation, since ITx has significantly less surgical risk and a less toxic immunosuppression regimen. Enhanced organ preservation via the proposed technology has the potential to increase the number of lifesaving ITx while improving outcomes. There have been 840 infusions in 340 recipients performed in North America (most of them in Canada) and 1380 in 775 recipients in Europe. ITx is an approved standard of care in Canada, the UK and a number of European countries. In the US, islet centers are preparing to file for FDA biologics licenses based on the favorable outcomes in the North American clinical trials; once those are granted, the numbers of US ITx are expected to increase substantially. The Giner Portable Pancreas Preservation System (P3S) will be the first complete, portable commercial system utilizing the persufflation organ preservation technique. The patent pending technology produces oxygen by electrochemical generation. The system supplies oxygen via gaseous perfusion ("persufflation") in which humid gas containing oxygen is flowed through the vasculature of the cold stored organ to minimize oxygen deprivation time. Persufflation enhances preservation of the pancreas as well as other organs. In the Phase I/II program, after development and fabrication, 8 portable persufflation units have been in preclinical and clinical use at seven facilities. The units have been utilized in over 55 procedures and over 1000 hours of operation including during seven airplane flights. The P3S has been approved for routine use on Air Canada. In preclinical testing for 24 hour preservation, the human pancreatic islet yield was 76% higher (p<0.003) relative to the current state-of-the-art preservation method at 10 hours; this higher yield would: (1) theoretically translate to 100% of current ITx recipients being insulin-free with a single ITx; and (2) increase the fraction of transplantable islet preparations from 42% to 81%. There is also evidence of enhanced islet quality based on insulin secretion assays. A Canadian clinical trial at University of Alberta, Edmonton started in October 2013 using the P3S. Four of the first four (100%) pancreatic persufflated in the pilot trial resulted in transplantable islet preparations compared to their historical standard of 42% transplantable preparations; also there was a significant increase in viability (as measured by OCR/DNA) at the day of transplant compared to historical control. Two of the three transplanted preparations have resulted in insulin independence for patients at ~ 2 months post-transplant. These early results are extremely encouraging and confirm our preclinical Phase II results. The goal of the Phase IIB program is to advance the technology to clinical implementation. At the end of Ph IIB, we expect to have a medical device that is ready: 1) for filing for 510K clearance in US and US clinical investigational use; and 2) to be sold commercially internationally in Canada, Europe and Australia with a CE Mark. The Ph IIB has 3 aims: 1) design and production of 12 pilot devices meeting international medical device standards; 2) preclinical testing with evaluation of islets from research-grade human pancreatic; and 3) support of clinical testing (study already approved and pilot study initiated) with ITx in Canada.