Data-Driven Tools to Accelerate the Clinical Translation of Novel Dental, Oral, and Craniofacial Biomaterials (Fast-Track - R44 - Clinical Trial Not Allowed)

Purpose This FOA seeks to accelerate the clinical translation of novel biomaterials for DOC applications through implementation of advanced data-driven tools specifically designed to overcome critical bottlenecks in R&D cycles that lead to delays in regulatory evaluations and translation to human use. This initiative leverages the FDA-CDRH’s Medical Device Development Tools (MDDT) program framework. Successful applications will integrate the FDA’s MDDT qualification process and related requirements into their research plan. Awardees will need to work closely with FDA’s MDDT Program to achieve FDA qualification of their proposed data-driven tool. The program goals include: 1) accelerate R&D cycles of biomaterials for DOC applications by de-risking potential safety and efficacious uncertainties through robust and predictive preclinical characterization; 2) support technical developments and validation activities needed to satisfy the FDA MDDT qualification process for proposed data-driven tools; 3) promote multi-domain collaborations between biomedical engineers, material scientists, software engineers, chemists, dentists, clinicians, biostatisticians, data analysts, biologists, and other relevant experts in academia and industry; and 4) build confidence in the use of data-driven technologies in biomaterials’ innovation by establishing pipelines of robust and validated tools that are qualified by the FDA. Background Data-driven technologies such as Artificial Intelligence (AI)/Machine Learning (ML) are catalyzing transformational advancements in scientific, clinical, and industrial domains through automation of process, extraction of patterns and inferences from complex datasets to enhance decision-making and problem-solving. Current data-driven software tools used in biomedical sciences can range in scope, technical approaches, and CoU, genomics research, protein structure prediction, and many others. The convergence of emerging data-driven technologies, such as AI/ML, data science, and computational modeling and simulation, is gaining rapid acceptance and adoption in biomedical research and clinical practices to enhance the efficiency, quality, and accuracy of decision-making and process management. These advancements call for the need to foster similar innovation in the R&D of biomaterials in dentistry and DOC domain overall. Furthermore, several data repositories and resources promoting the use of computational sciences for separate industrial materials development could be leveraged for available data. While biomaterials have dramatically improved in functionality and complexity, significant opportunities remain to enhance current R&D methods to ensure regulatory and clinical requirements are adequately satisfied. Major gaps in biomaterials R&D are attributed to complexities and inefficiencies in critical steps throughout their initial synthesis and formulation, the lack in predictiveness of preclinical characterization for safety and efficacy on clinical performance, and challenges with upscale manufacturing. Only a limited number of developments in the biomaterials domain currently involve the use of data- and computational-science tools to enhance formulation discovery and complex preclinical evaluations. Data-driven tools specifically designed and validated to support R&D of novel DOC biomaterials have the potential to drive breakthrough designs of high-quality biomaterials by empowering the aggregation, analysis and interpretation of complex datasets that drive solutions to pressing bottlenecks in product development, streamline regulatory approvals, and bridge gaps to clinical translation. The R&D cycle of DOC biomaterials requires consolidation and interpretation of different types of data to guide preclinical development, performance characterization, and upscale manufacturing based on existing knowledge and empirical data. However, despite many advancements in data-driven technologies fueling new innovations in life sciences, their adoption remains to be fully embraced in R&D of DOC biomaterials. Ensuring the safety and efficacy of biomaterials is central to the successful clinical translation of countless emerging devices in dentistry and other clinical specialties. This FOA promotes NIDCR’s collaboration with the FDA’s Center for Devices and Radiological Health (CDRH) Medical Device Development Tools (MDDT) program. The MDDT program was established for qualification of medical device development tools for use in evaluating medical devices subject to regulation by FDA/CDRH. An MDDT is a method, material, or measurement used to assess the efficacy, safety, and performance of a medical device. MDDTs can accelerate the device development process by providing developers with measurements and tools qualified by FDA that do not need to be re-evaluated within the CoU, which helps streamline/speed device development and FDA regulatory decision-making. Applicants should refer to FDA Guidance on MDDT Program for more details on the MDDT qualification process. Applicants are expected to adhere to the FDA’s MDDT qualification process as they work towards producing an FDA qualified MDDT. Research Objectives Research that encourages multi-domain investigators to collaborate in the development, customization, and validation of data-driven technologies and tools is expected to accelerate the R&D of novel DOC biomaterials. This initiative provides an opportunity to bridge knowledge and technology gaps to enhance capacity building and workforce development in data-driven technologies applied to biomaterials in alignment with the U. S. Department of Health and Human Services (HHS) AI Strategy and the NIH Office of Data Science Strategy. The following outcomes are expected from this initiative: Bring advanced data-driven technologies and computational material science to the forefront in R&D of DOC biomaterials. Yield significant reductions in the cost and time of regulatory approvals and in the clinical translation of safe and efficacious DOC biomaterials with improved clinical performance. Drive multi-domain collaborations and empower workforce development at the intersection of emerging data-driven and biomaterial science in DOC applications. Minimize use of laboratory animals and model organisms. Lead to new innovations in DOC biomaterials. Enhance the quality and efficiency of device evaluation and the FDA regulatory review process. Examples of research projects may include, but are not limited to the following: Develop predictive models for elution of substances (e.g., fluoride, calcium, potassium, etc.) from dental materials; antimicrobial activity of dental materials as a function of time; durability of dental materials in an oral environment; shelf-life based on chemical structure and use environment. Develop predictive tools to assess breakdown of biomaterials to help design better in vitro evaluations; device failure modes; early biocompatibility, risks, and toxicity of degradation byproducts; potential issues for reprocessing and reuse; characterize surface modifications of implanted or reusable devices (e.g., salt layers, sugars, diamond coating); overall process optimization and standardization; establish design and structural-functional relationships of biological and mechanical properties; degradation of biomaterial integrity as a function of biofilm challenge. This funding opportunity uses a Fast-Track mechanism that incorporates the submission and review process of both Phase I and Phase II applications together as one application. Fast-Track applications responding to this FOA require a fully developed Phase II component of the Phase I and Phase II components of the application must detail measurable milestones towards reaching Acceptance of the MDDT Qualification Plan by the FDA at the end of Phase I and eventual FDA Qualification of the MDDT by end of Phase II. Phase I and Phase II components of the application must include the following items: Milestone Plan, Qualification Strategy for Medical-Device-Development-Tool (MDDT) and Evaluation Plan (see Section IV. Application and Submission Information for more details). SBIR Phase I The Phase I will support activities related to the preparation and submission of an MDDT Qualification Plan to FDA within six months of receiving Phase I award. Phase I outcomes are expected to demonstrate technical feasibility of the proposed data-driven tool, and the acceptance by FDA of a comprehensive development strategy to achieving MDDT Qualification by the end of Phase II. Transitioning from SBIR-Phase I to SBRI-Phase II All projects must be driven by well-defined milestones for phase I and annual milestones for phase II. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. At the completion of phase I, the applicant will be required to submit a detailed transition request package, which will undergo an administrative review to determine whether the study will be awarded funding for phase II. Transitioning from Phase I to Phase II Award will be contingent on FDA’s acceptance of the MDDT Qualification Plan. Prospective applicants should note that initial funding of the phase I does not guarantee funding of the phase II. SBIR Phase II The Phase II will provide support to optimize the regulatory/clinical utility and value to unequivocally prove statistical significance of the tool in support of its CoU. During phase II, the preparation and submission of a Full Qualification Package to the FDA’s MDDT Program is required. The request package for MDDT Qualification must be submitted to FDA before the end of Phase II award including evidence collected according to the FDA-accepted Qualification Plan and FDA requirements for the MDDT Qualification Package Submission. Additional Information Applications responsive to this FOA must show understanding of the MDDT qualification process and include well-defined scientific and regulatory justifications for the proposed data-driven tool according to programmatic and technical milestones. A “MDDT Qualification Strategy” and an “Evaluation Plan” must be included. Applications without attachments for milestones, MDDT Qualification Strategy and an evaluation plan will be considered non-responsive to the FOA. The MDDT Qualification Strategy must describe the roadmap for the technical developments to obtain FDA’s qualification to address specific bottlenecks in medical device development and regulatory evaluation of new DOC biomaterials. The milestones plan must describe project milestones and the Go/No-Go criteria for each milestone. The Evaluation Plan must lay out a clear and concise plan to evaluate the scientific merit and feasibility of proposed specific aims using quantitative and qualitative metrics in Phase-I and -II components according to measurable milestones towards obtaining FDA qualification of the proposed data-driven tool.