102 Transcatheter Occluder Device for Paravalvular Leaks
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.
Over fifty thousand prosthetic heart valves are implanted in the United States annually. A discrete fraction develop significant regurgitation around the implant site, related to technical dehiscence or poor seating related to calcification, friability, or infection. The problem affects both mitral and aortic valves, whether implanted surgically or via a transcatheter route. The problem persists especially after surgically implanted valves despite technical refinement of transcatheter devices. Paravalvular regurgitation manifests as congestive heart failure from volume overload, or hemolytic anemia from mechanical cell injury. Surgical revision confers high morbidity and mortality. A variety of nitinol cardiac occluder devices have been employed off-label, but most are poorly suited for the application and none achieve simple and reliable occlusion.
The purpose of this solicitation is to support early-stage pre-clinical and clinical development of a purpose-built transcatheter occluder device for paravalvular leaks, to address this important unmet need.
The goal of the project is to develop a device for percutaneous closure of paravalvular leak. First a prototype would be developed and tested in vitro. Ultimately a clinical-grade device would undergo regulatory development for clinical testing in the USA.
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 a plan for a pre-submission meeting with the US Food and Drug Administration (FDA) in Phase I prior to the start of major engineering work or bench research. Offerors must include key personnel on the project with appropriate regulatory experience. Team members should have demonstrated experience with cardiovascular device product development, including permanent implants.
Offerors are advised to plan travel to NHLBI in Bethesda, Maryland, and are expected to plan for 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 catheter system for implantation of a paravalvular leak occluder. The offeror is expected independently to perform animal testing as needed to meet Phase I requirements.
Device requirements include:
• Up to 8Fr delivery system.
• Suitable to occlude regurgitation around surgically implanted aortic and mitral valve prostheses. Applicability to transcatheter valves is welcome.
• Ability to traverse complex geometry characteristic of paravalvular leaks.
• Ability to conform to complex and poorly visualized and highly variable regurgitant orifices.
• Demonstrating early hemostasis.
• Designs are encouraged that conform through bladder inflation or through expansion of superelastic materials or other novel approaches.
• Must be retrievable and removable before final implantation.
• Designs should avoid interference with function of the target prosthetic mechanical heart valves.
• Ability to reposition before final implantation is desirable.
• Low risk of embolization after implantation.
• Delivery designs are encouraged that retain delivery catheter position at the target (such as with a buddy guidewire) until conclusion of the procedure.
• Devices should be conspicuous during positioning and after final implantation, with attention to challenges imposed by metallic surgical valves.
• The devices should not impose an undue risk of thromboembolism and stroke after implantation.
• Implants should be MRI compatible so that cardiac function and flow can be measured unimpeded after implantation using MRI. 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 system should be accompanied by a proposed robust methodology or device to select the appropriate device size.
Expected deliverables include:
• 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.
• A final prototype with phantom testing.
Final payment is contingent on meeting all of the above requirements.
Consideration for transition to Phase II funding will include progress toward 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, if required, a 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 if required.
• chronic or acute GLP animal studies as required.
• 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 Bridge (http://1.usa.gov/1q9yTyP) and Phase IIB Small Market Award (http://1.usa.gov/1v0Wxn1) programs to support additional development beyond Phase II. The NHLBI Phase IIB programs provide up to an additional $3M over 3 years, with an expectation that applicants secure independent third-party investor funds.
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID)
The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. For more than 60 years, NIAID research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world. To learn more about the NIAID, please visit our web page at http://www.niaid.nih.gov/about/whoWeAre/Pages/moreWhoWeAre.aspx.