Blueprint Medtech: Small Business Translator (U44 - Clinical Trial Optional)

Blueprint MedTech The NIH Blueprint for Neuroscience Research is a collaborative framework through which 14 NIH Institutes, Centers and Offices jointly support neuroscience-related research, with the aim of accelerating discoveries and reducing the burden of nervous system disorders (for further information, see http://neuroscienceblueprint.nih.gov/). Innovators developing groundbreaking medical device technologies face a number of challenges along the translational path from bench to bedside. The Blueprint MedTech program is an NIH incubator that aims to address such challenges and support the innovators by accelerating the development of cutting-edge medical devices to diagnose and treat disorders of the nervous system. The mission of the program is to catalyze the translation of novel neurotechnologies from early-stage development to first-in-human clinical studies. The program will provide: (a) non-dilutive funds to support medical device development activities led by investigators, and (b) additional resources and support services including, but not limited to: Planning resources to support concept development, team building, needs assessment, and other early translational activities. Streamlined access to translational services and expertise (e.g., design and prototyping, bench testing, large animal testing, biocompatibility assessment, manufacturing, medical monitoring). Assistance from consultants (e.g., on regulatory, reimbursement, intellectual property, commercialization, and strategic partnership issues). Advice from industry experts (e.g., meetings with an external oversight committee). The overarching goal of the Blueprint MedTech program is to accelerate patient access to groundbreaking, safe, and effective medical devices. The program will provide support to sufficiently develop and de-risk technologies to the point where additional investments are warranted from industry partners, investors, and government. A. Overview The purpose of this Funding Opportunity Announcement (FOA) is to support SBCs in pursuing translational activities and clinical studies to advance the development of therapeutic, and diagnostic devices for disorders that affect the nervous or neuromuscular systems. Activities supported by this FOA include implementation of clinical prototype devices, non-clinical safety and effectiveness testing, design verification and validation activities. Additional activities include obtaining an Investigational Device Exemption (IDE) for a Significant Risk (SR) study or Institutional Review Board (IRB) approval for a Non-Significant Risk (NSR) study, as well as support for a subsequent clinical feasibility study. The clinical study is expected to provide information about the device function or final design that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use. All projects will be submitted as SBIR Fast-Track applications. The Phase I project will support non-clinical translational device activities to obtain an IDE and IRB approval for an SR clinical study, or to obtain IRB approval for an NSR clinical study. The duration of SBIR Phase I project will depend on the maturity of the project at entry and can last up to two years. The Phase II project will support a clinical study and can last up to three years. The total project period (including both phases) must not exceed five years. Projects for which only a clinical phase is proposed are outside of the scope of this funding opportunity. Only Phase I projects that have met specific criteria (see below) will be eligible for transition to Phase II after NIH administrative review. Furthermore, ethical considerations are intrinsic to the responsible conduct of neuroscience research and the translation of neuroscience advances (scientific and technological) into clinical practice. It is expected the immediate next steps following completion of the clinical feasibility study supported under this cooperative agreement will be: a marketing application if only a clinical feasibility study or experience is needed to demonstrate the device is safe and effective. a larger clinical trial that will lead to a marketing application, or device design decisions made based on the information and data collected. This FOA will utilize a Small Business Innovation Research (SBIR) U44 cooperative agreement. As a cooperative agreement, this FOA supports milestone-driven projects and involves NIH program staff’s participation in negotiating project and milestone plan before award, monitoring the research progress, and making go/no-go decisions. The expectations of the program are in line with those of industry regarding the advancement of devices through the developmental and translational pipelines. As such, an inherent rate of attrition is possible within this program. An objective of the SBIR and STTR programs is to foster and encourage participation in innovation and entrepreneurship by socially and economically disadvantaged persons and women-owned small businesses. This PAR encourages applications from diverse teams of investigators,including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds B. Scope Projects must focus on a disorder that falls within the mission of participating NIH Blueprint Institutes and Centers. It is expected that devices within the scope of this program either: are very close to the 'final system' and manufactured using very close to the same manufacturing process as the device to be marketed or studied in a larger clinical trial following the completion of this project; or have received Pre-Submission feedback from the FDA (see FDA/CDRH Q-Submission website and CDRH-learn website, Q-submissions for additional resources); or require early feasibility clinical data to inform the final device design or manufacturing processes. C. Entry criteria Applicants to the Blueprint MedTech program must include novel medical device technologies that will advance upon current neurotechnology (see non-responsive criteria below). Applicants should clearly define the current state of the art and highlight how their proposed technology will advance patient care. Responsive applications should propose medical devices, expected to be regulated by the FDA, with first-of-its-kind technologies, unique and novel intended use, new safety questions, and/or new regulatory questions. Responsive applications may also pivot and refine existing technologies toward new intended use and/or use in novel settings (e.g., innovating and translating a neuromodulation device approved for healthcare-setting only to home-use). Proposed medical devices and their indications will likely follow De Novo or Premarket Approval (PMA) regulatory pathways. Medical devices with indications that may fit within an existing 510(k) pathway may also be accepted, as long as the application can demonstrate a clear clinical and technological innovation beyond the state of the art of existing FDA-cleared predicates. Such devices should be reasonably expected to provide new clinically meaningful diagnostic or therapeutic options or improve the benefit-risk profile of a treatment or diagnostic through substantial safety innovations. It is recommended that applicants reach out to the NIH program staff listed at the bottom of this funding opportunity to discuss responsiveness criteria with respect to proposed technologies and indications. For entry to the program, projects should have: Comprehensive supporting data based on bench, in vitro, and/or in vivo models representative of the intended patient population and indication. Identified one or more clinically meaningful device outcome measures based on input from key stakeholders (e.g., clinicians, patients, and caregivers) as well as supporting literature. A compelling case for a successful IDE submission for an SR study, or IRB approval for an NSR study at the end of SBIR Phase I. Required regulatory approvals for clinical studies must be received prior to the start of the SBIR Phase II. Applicants are encouraged, but not required, to consult with FDA via a Pre-Submission meeting, study risk designation request, and/or 513(g) submission prior to applying for funding through this grant mechanism. Applicants who do not have sufficiently relevant feedback from the FDA regarding all planned activities prior to application for funding will be expected to do so as the first milestone of the SBIR Phase I award. Funding may be restricted to a maximum of $100,000 in direct costs until FDA feedback that is consistent with the likely success of the regulatory path to market and overall device development plan outlined in the grant application is received. In the event that FDA feedback is not consistent with the plans in the grant, program staff will evaluate the concerns and change of scope that would be needed and work with the investigators to determine the most appropriate course of action. Any remaining funds associated with the original award will not be released. D. Phases SBIR Phase I scope: Examples of studies that may be proposed during SBIR Phase I include, but are not limited to: Non-Good Laboratory Practice (GLP) animal studies to develop surgical techniques relevant to the device, optimize relevant therapeutic or diagnostic parameters, and refine device design as necessary for subsequent GLP testing or additional clinical studies for regulatory approval. Bench-top and animal testing to demonstrate compliance with FDA Recognized Standards. GLP compliant large animal model safety and/or testing of an implanted device. Activities to become current Good Manufacturing Practice (cGMP) compliant. Activities to bring the development process under Design and Quality Systems Control. Studies addressing usability/acceptability. Device, software, firmware, and cybersecurity design verification and validation activities. Development of packaging, connectors, and other accessories necessary for the translation of this technology. Regulatory activities, including pre-submission meetings with FDA, IDE submission, or other FDA regulatory submissions (e.g., Humanitarian Device Exemption (HDE), Request for Risk Designation, 513(g) submission). SBIR Phase II scope: SBIR Phase II will support a clinical study that will lead to either: A marketing application if the clinical study is sufficient to demonstrate device safety and effectiveness for regulatory approval, or A larger clinical study that will lead to a marketing application; or Use of the clinical experience to inform device design decisions Examples of studies that may be proposed during SBIR Phase II include, but are not limited to: Optimization of the device design with respect to the human functional anatomy. Identification of the most simple, reliable, and cost-effective device configuration for more advanced clinical studies and eventual market approval. Studies of the key physiological variables that may impact the function of the device in humans. Initial assessments of device safety are expected, but only in conjunction with obtaining enabling data about device design or function E. Non-Responsive Activities Applications that include the following activities will be considered non-responsive and will be withdrawn and not reviewed: Animal model development: all in vivo models must be established and characterized, and available to the applicant; Efforts to develop neurotechnology for fundamental study of the nervous system; Fundamental basic/applied research projects that employ existing market approved devices for their labeled uses; Projects focused on technologies for augmentation of healthy individuals; Delayed-onset clinical studies; Device technologies where the SBC does not have the needed intellectual property (IP) to enable further development/commercialization; Device technologies not regulated by the FDA. Applications that do not include the following will also be considered incomplete: The following other attahcments: Gantt Chart, Long-term care plan, Resource Checklist; A milestone plan; It is recommended that applicants reach out to the NIH program staff listed at the bottom of this funding opportunity to discuss responsiveness criteria with respect to proposed technology and indications F. Milestones Because device development is an inherently risky process, it is anticipated that there may be attrition as projects progress. Applications must propose one or more milestones for each objective in each year of the project. Milestones are goals that quantitatively measure success and efficacy that will be used for go/no-go decision-making for the project (see below for details). For each objective, provide details on methods, assumptions, experimental designs, and data and statistical analysis plans. Specify the quantitative criteria for measuring success and the rationale used to develop and justify the criteria identified. Quantitative criteria should be robust and consistent with the state-of-the-art in the field. Applicants are encouraged to read examples of milestones (e.g., https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library/Devices-Milestones). NIH program staff will contact the applicant to discuss the project and any changes prior to funding the application, including negotiation of the proposed milestones. The final agreed upon and approved milestones will be specified in the Notice of Award (NoA). Progress towards achievement of the final set of milestones will be evaluated yearly by NIH program staff. Program staff may involve independent consultants or subject matter experts with relevant expertise. If justified, future milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project will be discontinued. In addition to milestones, the decision to continue funding will also be based on: a robust data package that allows for adequate interpretation of results (regardless of whether they have been captured in the milestones), overall progress, portfolio balance and program priorities, competitive landscape, and availability of funds. NIH encourages rigor and reproducibility of observed results. In some cases, conducting additional critical experiments will be important for NIH to have confidence in making a funding decision. SBIR Phase I to Phase II transition: An administrative review will be conducted by program staff, with potential input by independent consultants, to decide whether the Phase I project will be transitioned to the Phase II project based on the following: Successful achievement of the Phase I milestones; Likelihood of success in clinical testing; Competitive landscape; Program priorities and current portfolio balance (for funded projects, search NIH RePORTER https://projectreporter.nih.gov/); For significant risk studies, documentation of final or conditional approval of the IDE from the FDA; IRB approval(s); Submission of the final clinical protocol and supporting documents to NIH ; Feedback on activities involving human subjects obtained from the NIH Safety and Risk Assessment Committee (SARAC); Agreement on updated timeline, milestones and budget for the clinical study, and Availability of funds. G. Quality and Compliance Requirements The use of the Design Control and Quality Systems processes (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/design-control-guidance-medical-device-manufacturers) to the degree specified by the FDA is required. Intermediate steps in the Design Control process (e.g., design reviews, design verification, design validation, and design transfer activities) where appropriate, and IDE submission should be represented in the annual milestones. NIH recognizes that the degree to which Design Controls and Quality Systems processes are required by the FDA may vary substantially depending on the specific device. Investigators are encouraged to discuss these issues with the FDA and regulatory consultants prior to submitting an application so the extent to which these processes are required is clearly defined and verifiable in the application. Applicants should consider the Quality System requirements at the IDE stage (i.e., design controls) when preparing their device development activities. Applicants should consider Guidelines and Policies for Monitoring Clinical Research in the formation of a plan for data and safety monitoring as required by the appropriate IC. I. Pre-application Consultation As an U44 cooperative agreement, NIH program staff will be involved in the negotiation and execution of the project. When possible applicants are strongly encouraged to consult with NIH program staff early in the process of planning an application; this provides the opportunity for the SBC to receive further guidance on program scope, goals, and developing appropriate milestones. Applicants should contact program staff at least 12 weeks before a receipt date. J. Institute Statements of Interest Refer to Blueprint MedTech website for specific IC requirements and interest statements: