Development of a pediatric transcatheter pulmonary valve system

 描述（由申请人提供）：美国每年约有40，000名婴儿和全球超过100万名婴儿出生时患有先天性心脏缺陷（CHD）。据估计，20%的CHD儿童患有特定的心脏缺陷，涉及右心室流出道（RVOT）和肺动脉瓣。这些儿科患者通常在其一生中经历多次侵入性心脏直视手术，以重建从心脏到肺部的正常血流。 经导管肺动脉瓣置换术（TPVR）正在成为外科手术的一种安全、微创的替代方法。然而，市场上唯一可用的TPVR器械（Medtronic的Melody瓣膜）有几个局限性：它只能用于肺动脉直径小于24.5 mm且没有较大尺寸瓣膜的患者;该器械是一种带有22 Fr输送系统的笨重器械，不能用于体型较小的儿科患者;其支架断裂已被广泛报道。因此，对于具有较小卷曲轮廓、较大尺寸和良好耐久性的TPVR装置存在明显未满足的市场需求。基于在心脏瓣膜生物力学和医疗器械设计方面的广泛学术、临床和工业经验，Dura Biotech的团队发明了硬脑膜瓣叶技术（DVLT），用于开发低切迹TPVR，该技术可适用于从幼儿到成人的各种肺动脉直径范围内的各种解剖结构。新型DVLT设计-在瓣叶上增加加强悬挂结构-可以优雅地减小瓣叶厚度，而不会增加瓣叶峰值应力集中，这是影响机械损伤导致瓣叶失效的关键因素。采用DVLT设计，TPVR器械可以更小，瓣叶更薄，同时保持耐用性。 该SBIR快速通道项目的目标是开发和商业化这一改变范式的Dura TPVR器械。在项目的第1阶段，我们提议通过一系列计算和实验测试来最终确定TPVR器械的瓣膜和支架设计，以满足客户要求以及联邦药品监督管理局（FDA）规定的所有标准。在第2阶段，整个最终TPVR系统将接受验证和确认测试，然后通过动物研究评估可行性和安全性。最后，Dura Biotech将制定质量体系启动策略，并准备向FDA提交监管申请。该项目的成功完成将产生一种创新的TPVR器械，用于治疗尚未开发的RVOT和PV疾病患者人群，并改善患者结局。

 DESCRIPTION (provided by applicant): Approximately 40,000 babies in the US and over 1 million babies worldwide each year are born with congenital heart defect (CHD). It is estimated that 20% of CHD children have specific heart defects that involve the right ventricular outflow tract (RVOT) and pulmonary valve. These pediatric patients are typically subjected to multiple invasive open-heart surgeries throughout their lifetime in order to reestablish normal blood flow from the heart to the lungs. Transcatheter pulmonary valve replacement (TPVR) is emerging as a safe, less invasive alternative to surgical procedure. However, the only available TPVR device in the market, the Melody valve from Medtronic, has several limitations: it can only be used for patients who have a pulmonary diameter less than 24.5 mm and does not have a larger size valve; the device is a bulky device with a 22 Fr delivery system, which cannot be used for small pediatric patients; and its stent fracture has been extensively reported. Thus, there is a clear unmet market need for a TPVR device with smaller crimped profile, larger size and good durability. Building upon extensive academic, clinical and industrial experiences on heart valve biomechanics and medical device designs, the team at Dura Biotech has invented Dura Valve Leaflet Technology (DVLT) for developing low profile TPVRs that could fit within the various anatomic configurations across a range of pulmonic diameters that extended from young child to full adult size. The novel DVLT design-adding the reinforcement suspension structures on the valve leaflets-can elegantly reduce leaflet thickness without increasing leaflet peak stress concentration, which is a key factor influencing mechanical damage leading to valve leaflet failure. With the DVLT design, TPVR device can be smaller with thinner leaflets while maintaining durability. The goal of this SBIR Fast-Track project is to develop and commercialize this paradigm- changing Dura TPVR device. In phase 1 of the project, we proposed to finalize the valve and stent designs of the TPVR device through a series of computational and experimental tests to meet customer requirements as well as all criteria specified by the Federal Drug Administration (FDA). In phase 2, the entire finalized TPVR system will be subjected to verification-and-validation tests and then evaluated for feasibility and safety through an animal study. Lastly, Dura Biotech will develop a strategy for quality system initiation and prepare for regulatory submission to FDA. Successful completion of this project will yield an innovative TPVR device to treat an untapped population of patients with RVOT and PV diseases and improve patient outcomes.