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1型糖尿病的子集，标准胰岛素治疗是不够的。I是胰腺移植的一种有前途的替代方案，因为ITx具有显著更低的手术风险和更低毒性的免疫抑制方案。通过所提出的技术增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（大多数在加拿大），340名接受者接受了840次输注，欧洲775名接受者接受了1380次输注。ITx是加拿大、英国和一些欧洲国家批准的标准治疗。在美国，胰岛中心正准备根据北美临床试验的有利结果申请FDA生物制剂许可证;一旦获得许可，美国ITx的数量预计将大幅增加。Giner便携式胰腺保存系统（P3 S）将是第一个完整的，便携式的商业系统，利用吹气器官保存技术。这项正在申请专利的技术通过电化学发电来生产氧气。该系统通过气体灌注（“充注”）供应氧气，其中含有氧气的潮湿气体流过冷藏器官的脉管系统以最小化缺氧时间。灌注增强了胰腺和其他器官的保存。在I/II期项目中，在开发和制造后，8台便携式充气装置已在7家机构进行临床前和临床使用。这些装置已经在超过55个程序和超过1000小时的操作中使用，包括7次飞机飞行。P3 S已被批准用于加拿大航空的日常使用。在24小时保存的临床前测试中，相对于目前最先进的保存方法，人胰岛产量在10小时时高出76%（p<0.003）;这种更高的产量将：（1）理论上转化为100%的当前ITx接受者被 不含胰岛素，具有单一ITx;和（2）将可移植胰岛制剂的分数从42%增加到81%。也有证据表明，基于胰岛素分泌测定的胰岛质量提高。加拿大阿尔伯塔大学埃德蒙顿的一项临床试验于2013年10月开始使用P3 S。在初步试验中，前4例（100%）胰腺灌注导致 可移植的胰岛制剂与其历史标准42%的可移植制剂相比;与历史对照相比，在移植当天存活率（通过OCR/DNA测量）也有显著增加。三种移植制剂中的两种在移植后约2个月时使患者实现胰岛素非依赖性。这些早期结果非常令人鼓舞，并证实了我们的临床前II期结果。IIB期项目的目标是将该技术推向临床应用。在II B期结束时，我们预计医疗器械将准备就绪：1）在美国和美国临床研究中申请510 K许可; 2）在加拿大、欧洲和澳大利亚进行商业销售，并获得CE认证。Ph IIB有三个目标：1）设计和生产12个符合国际医疗器械标准的中试器械; 2）临床前测试，评估研究级人类胰腺的胰岛; 3）支持加拿大ITx的临床测试（研究已获批准，中试研究已启动）。

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.