Development of a pediatric transcatheter pulmonary valve system

 描述(申请人提供)：美国每年约有40,000名婴儿患有先天性心脏病(CHD)，全球每年有超过100万名婴儿出生。据估计，20%的CHD儿童有特殊的心脏缺陷，累及右室流出道(RVOT)和肺动脉瓣。这些儿科患者通常在其一生中接受多次侵入性心内直视手术，以重建从心脏到肺的正常血流。经导管肺动脉瓣置换术(TPVR)是一种安全、创伤较小的外科手术替代方法。然而，市场上唯一可用的TPVR设备--美敦力的Melody瓣膜--有几个限制：它只能用于肺直径小于24.5 mm的患者，并且没有更大通径的瓣膜；该设备体积较大，具有22Fr输送系统，不能用于小型儿科患者；其支架断裂已被广泛报道。因此，市场对卷曲轮廓更小、尺寸更大、耐用性更好的TPVR设备的需求显然尚未得到满足。在心脏瓣膜生物力学和医疗器械设计方面丰富的学术、临床和工业经验的基础上，杜拉生物技术的团队发明了杜拉瓣叶技术(DVLT)，用于开发低轮廓TPVR，这种技术可以适应从幼儿到完全成人大小的各种肺直径的解剖结构。这种新颖的DVLT设计--在阀瓣上增加增强悬挂结构--可以在不增加阀瓣峰值应力集中的情况下优雅地减小阀瓣厚度，这是导致机械损伤导致阀瓣失效的关键因素。有了DVLT设计，TPVR设备可以更小，更薄的小叶，同时保持耐用性。该SBIR快速通道项目的目标是开发这种改变范式的杜拉TPVR设备并将其商业化。在项目的第一阶段，我们建议通过一系列计算和实验测试来最终确定TPVR设备的瓣膜和支架设计，以满足客户的要求以及联邦药品管理局(FDA)指定的所有标准。在第二阶段，整个最终的TPVR系统将接受验证和确认测试，然后通过动物实验评估其可行性和安全性。最后，杜拉生物技术公司将制定质量体系启动战略，并准备向FDA提交监管报告。该项目的成功完成将产生一种创新的TPVR设备，用于治疗尚未开发的RVOT和PV疾病患者，并改善患者的预后。

 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.