Description:
101 Membranous Ventricular Septal Defect (pmVSD) Transcatheter Occluder System
Fast-Track proposals will be accepted.
Direct-to-Phase II proposals will be accepted.
Number of anticipated awards: 1
Budget (total costs):
Phase I: up to $400,000 for up to 21 months
Phase II: up to $3,000,000 for up to 36 months
PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.
Summary
Ventricular septal defect is the most common congenital heart defect. Membranous-type ventricular septal defect (pmVSD) accounts for over two thirds of ventricular septal defects, and approximately half require repair. Surgical repair is morbid, and may require two staged surgical procedures. No suitable device is marketed for transcatheter repair of pmVSD. Commercial development of catheter-based devices to treat structural heart disease in children is limited by the relatively small market size and the relatively large upfront costs.
The purpose of this solicitation is to support early-stage pre-clinical and clinical development of a transcatheter device system to treat pmVSD without surgery.
Project Goals
Page 114
The goal of the project is to develop a device for percutaneous closure of membranous VSD in infants and children, with an acceptable low rate of complete heart block compared with surgical closure. First a prototype would be developed and tested in animals, and ultimately a clinical-grade device would undergo regulatory development for clinical testing at NIH.
Offerors are encouraged to include concrete milestones in their proposals, along with detailed research and development plans, risk analysis, and contingency plans, both for Phase I and Phase II.
Proposals must include a detailed description of the regulatory strategy, including plans for a pre-submission meeting with the US Food and Drug Administration (FDA) in Phase I. Offerors must include key personnel on the project with appropriate and relevant regulatory experience.
Offerors are advised to plan travel to NHLBI in Bethesda, Maryland, and are expected to plan meetings at project initiation, mid-project to determine what iteration is necessary, and at project completion.
Phase I Activities and Expected Deliverables
A Phase I award would support the development and testing of a pmVSD occluder prototype suitable for children and newborn infants. The NHLBI Division of Intramural Research laboratory offers to test a final prototype in vivo, at no expense to the offeror. The offeror is expected independently to perform animal testing as needed to meet Phase I requirements.
Device requirements include:
• A design specifically to achieve occlusion of membranous-type ventricular septal defects in children and newborn infants.
• The implant should accommodate a range of defects average diameters sized 2mm to 18mm, using multiple device sizes if necessary.
• The implant should be designed specifically to minimize or avoid conduction system injury that would risk immediate or late complete heart block.
• The implant should have mechanisms or a range of morphologies to avoid entrapment or distortion of the aortic valve or to avoid late injury to the aortic valve root or leaflets.
• The implant should be available with transmyocardial or interventricular “neck” length and width dimension.
• The implant should conform to ventricular cavities without causing geometric distortion or obstruction of ventricular outflow tracts.
• The delivery system catheter outer diameter must be 9Fr or smaller and should be suitable for fully transcatheter repair without requiring surgical cardiac exposure.
• The implant and delivery system should avoid entrapment or early/late injury to tricuspid valve with attention to aneurysmal septal segments.
• The proposed solution should have a mechanism to assure proper orientation if that is important to the functionality of specific design.
• Designs amenable to both antegrade and retrograde delivery are desirable.
• The delivery system should secure against unplanned release.
• Proposals should include specific plans for operator recovery of the device if it embolizes after release.
• Implants must be MRI compatible so that cardiac function and flow can be measured unimpeded after implantation using MRI, and MRI conspicuity is desirable.
• The delivery system and implant must be conspicuous under the proposed image-guidance modality whether ultrasound or X-ray, and must be conspicuous under X-ray after release.
• The delivery system should be designed to mitigate hemodynamic embarrassment caused by interruption of tricuspid valve function during implant procedures.
• The device should accomplish acute or subacute occlusion without early or late thromboembolism, and proposals should specifically address these considerations.
• The system should be accompanied by a proposed robust methodology or device to select the appropriate device size.
• Build of a phantom for bench testing of the device design(s), retrieval tool, and size selection tool/methodology.
Page 115
• The offeror must independently demonstrate satisfactory device performance in VSD, preferably pmVSD, in vivo.
• A comprehensive report of test results, including in vivo test results if not performed at NHLBI.
• A detailed report of pre-submission interactions with the FDA Center for Devices and Radiological Health (CDRH), indicating a sufficiently mature device and identifying requirements for Investigational Device Exemption (IDE) development under Phase II, including meeting minutes, if available.
Final payment is contingent on meeting all of the above requirements.
Consideration for transition to Phase II funding will include regulatory progress toward US market access. Consideration may include the status of the contractor’s interactions with the FDA. NHLBI encourages contractors to consider requesting designation to the FDA’s Expedited Access for PMA Devices (EAP) program (http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM393978) during the Phase I award period.
Phase II Activities and Expected Deliverables
In addition to meeting all requirements specified for Phase I, the Phase II award would allow mechanical and safety testing and regulatory development for the device to be used in human investigation. The NHLBI Division of Intramural Research laboratory offers but does not require to perform an IDE clinical trial at no cost to the awardee. Activities in Phase II should align with the required testing and development milestones agreed upon with the FDA in Phase I.
Complete IDE documentation and license and a suitable supply of clinical materials would constitute the final deliverable. The offeror will provide a complete report of prior investigation along with all other elements of the IDE application and accompanying regulatory correspondence. For all purposes, a humanitarian device exemption (HDE) or an expedited Premarket Approval (PMA) would be considered responsive in place of IDE.
The offeror should provide clear project milestones that trigger review and payment, along with detailed research and development plans, risk analysis, and contingency plans. Representative project milestones include, not necessarily sequentially:
• a device build and short-term survival study to identify additional failure modes.
• elements of a quality system including product specification, design and failure mode analysis, design verification and validation and test plan, biocompatibility and sterility assessment and plan, design review, design freeze, design transfer to manufacturing.
• manufacturing plan.
• iterative ex vivo testing such as animal explants.
• iteration for unexpected design or device failure.
• pre-submission meetings with FDA.
• modeling and fatigue study for chronic implant.
• chronic GLP animal studies.
• design of clinical protocol including informed consent, risk analysis for early feasibility, and case report form, whether or not conducted in collaboration with NHLBI Division of Intramural Research laboratory.
• preparation of IDE.
• submission and resubmission of IDE.
• manufacturing of test articles.
The offeror is expected to conduct animal experiments and provide care as required to obtain the IDE. The offeror is advised to propose how to proceed in case of hold from FDA.
Offerors are encouraged to consider the NHLBI Phase IIB Small Market Award (http://1.usa.gov/1v0Wxn1) program to support additional development beyond Phase II. The NHLBI Phase IIB Small Market Award provides up to an additional $3M over 3 years, with an expectation that applicants secure independent third-party investor funds.
