Part 1. Overview Information

Key Dates

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

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.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria:

1. Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;
2. Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there must be less than 50 percent participation by foreign business entities in the joint venture;
3. 1. SBIR and STTR. Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), an Indian tribe, ANC or NHO (or a wholly owned business entity of such tribe, ANC or NHO), or any combination of these; OR
   2. SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern, unless that single venture capital operating company, hedge fund, or private equity firm qualifies as a small business concern that is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States; OR
   3. SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with 121.705(b) concerning registration and proposal requirements.
4. Has, including its affiliates, not more than 500 employees.

   If the concern is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these falls under 3 (ii) or 3 (iii) above, see Section IV. Application and Submission Information for additional instructions regarding required application certification.

If an Employee Stock Ownership Plan owns all or part of the concern, each stock trustee and plan member is considered an owner.

If a trust owns all or part of the concern, each trustee and trust beneficiary is considered an owner.

Definitions:

• Hedge fund has the meaning given that term in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The hedge fund must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity firm.
• Private equity firm has the meaning given the term private equity fund in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The private equity firm must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Venture capital operating company means an entity described in 121.103(b)(5)(i), (v), or (vi). The venture capital operating company must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• ANC means Alaska Native Corporation.
• NHO means Native Hawaiian Organization.

SBCs must also meet the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.

Small business concerns that are more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these are NOT eligible to apply to the NIH STTR program.

Phase I to Phase II Transition Rate Benchmark

In accordance with guidance from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of 2011. This Transition Rate requirement applies to SBIR and STTR Phase I applicants that have received more than 20 Phase I awards over the past 5 fiscal years, excluding the most recently-completed fiscal year. For these companies, the benchmark establishes a minimum number of Phase II awards the company must have received for a given number of Phase I awards received during the 5-year time period in order to be eligible to apply for a new Phase I award Fast-Track, or Direct Phase II (if available). This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5 year period.

Companies that do not meet or exceed the benchmark rate will not be eligible to apply for a Phase I Fast-Track, or Direct Phase II (if available) award for a period of one year from the date of the application submission. The Transition Rate is calculated as the total number of SBIR and STTR Phase II awards a company received during the past 5 fiscal years divided by the total number of SBIR and STTR Phase I awards it received during the past 5 fiscal years excluding the most recently-completed year. The benchmark minimum Transition Rate is 0.25.

SBA calculates individual company Phase I to Phase II Transition Rates daily using SBIR and STTR award information across all federal agencies. For those companies that have received more than 20 Phase I awards over the past 5 years, SBA posts the company transition rates on the Company Registry at SBIR.gov. Information on the Phase I to Phase II Transition Rate requirement is available at SBIR.gov.

Applicants to this FOA that may have received more than 20 Phase I awards across all federal SBIR/STTR agencies over the past five (5) years should, prior to application preparation, verify that their company’s Transition Rate on the Company Registry at SBIR.gov meets or exceeds the minimum benchmark rate of 0.25.

Phase II to Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including NIH, SBIR/STTR Programs are implementing the Phase II to Commercialization Rate benchmark for Phase I applicants, as required by the SBIR/STTR Reauthorization Act of 2011. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537).

This requirement applies to companies that have received more than 15 Phase II awards from all agencies over the past 10 years, excluding the two most recently-completed Fiscal Years. Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0.15 (15%) patents per Phase II award resulting from these awards. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10 year period, excluding the two most recently-completed Fiscal Years.
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Information on the Phase II to Commercialization Benchmark is available at SBIR.gov.

Applicants to this FOA that may have received more than 15 Phase II awards across all federal SBIR/STTR agencies over the past ten (10) years should, prior to application preparation, verify that their company’s Commercialization Benchmark on the Company Registry at SBIR.gov meets or exceeds the benchmark rate listed above.

Applicants that fail this benchmark will be notified by SBA annually and will not be eligible to apply for New Phase I, Fast-track or Direct Phase II (if applicable) awards for a period of one year.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, may be allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• SBA Company Registry See Section IV. Application and Submission Information, SF424(R&R) Other Project Information Component for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a UEI to complete this registration. SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PDs/PIs, at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur.

The SF424 (R&R) SBIR/STTR Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the SF424 (R&R) SBIR/STTR Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and any other HHS funding opportunity, including the SBIR and STTR Parent announcements.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review.

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II or IIB support, a Phase I awardee should submit a Phase II application, and a Phase II awardee should submit a Phase IIB application, within the first six due dates following the expiration of the Phase I or II budget period, respectively.

In Phase I, normally, two-thirds or 67% of the research or analytical effort is carried out by the small business concern. The total amount of all consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 33% of the total amount requested (direct, F&A/indirect, and fee).

In Phase II, normally, one-half or 50% of the research or analytical effort is carried out by the small business concern. The total amount of consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

Deviations from these requirements may be considered on a case by case basis. Please contact a program officer for additional information. Deviations must be approved in writing by the Grants Management Officer (GMO) after consultation with the agency SBIR Program Manager/Coordinator. In Phase I and Phase II, at least 40% of the research or analytical effort must be performed by the small business concern and at least 30% of the research or analytical effort must be performed by the single, partnering research institution. The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct, F&A/indirect costs, and fee attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of the SF424 (R&R) application forms.

Additional details are contained in the SF424 (R&R) SBIR/STTR Application Guide.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Yasaman Shirazi, PhD

Chief, Scientific Review Branch, NIDCR, NIH

Telephone: 301-594-5593
Email: [email protected]

All page limitations described in the SF424 (R&R) SBIR/STTR Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) SBIR/STTR Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed with the following additional instructions:

Other Attachments:

1. SBIR Application Certification for small business concerns majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms

Applicant small business concerns that are majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms (e.g. majority VCOC-owned) are required to submit a Certification at time of their application submission per the SBIR Policy Directive. Follow the instructions below.

Applicants small business concerns who are more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these (i.e. NOT majority VCOC-owned) should NOT fill out this certification and should NOT attach it their application package.

1. Download the VCOC Certification.pdf at the NIH SBIR Forms webpage.

2. Answer the 3 questions and check the certification boxes.

3. The authorized business official must sign the certification.

4. Save the certification using the original file name. The file must be named SBIR Application VCOC Certification.pdf . DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

5. When you are completing the application package, attach this certification as a separate file by clicking "Add Attachments" located to the right of Other Attachments field on the Research and Related Other Project Information form.

Milestone Plan (Required 3 page limit)

The filename "Milestone Plan" should be used to name this attachment. A Milestone Plan must be included with the application. The Milestone Plan must use clear go/no-go criteria that are quantifiable towards achieving FDA’s qualification of the proposed data-driven tool to address specific bottlenecks in R&D cycles and regulatory evaluations of new DOC biomaterials. Phase I and Phase II milestones must clearly describe the alignment of the proposed technology with solutions to bottlenecks in the regulatory evaluation of novel biomaterials in line with FDA’s MDDT Program framework.

Phase I Milestones must include:

• Demonstration of scientific and technical merit and feasibility of proposed data-driven tool for specific CoU.

• Development of a strategy/plan and timeline to summit a Qualification Plan that meets the criteria defined by the FDA MDDT program, including plans to engage with the FDA to refine and execute an appropriate MDDT qualification strategy.
• Preparation and submission of an MDDT Qualification Plan to FDA within six months of receiving Phase I award. For additional details review Qualification of Medical Device Development Tools - Guidance for Industry, Tool Developers, and Food and Drug Administration Staff.
• Identification of precision and performance-level parameters necessary for the dataset and algorithms to become a relevant tool for preclinical testing and regulatory evaluation of novel DOC biomaterials. This may include a sizing analysis to determine the size of a pivotal dataset following the algorithm-assessment plan.
• Development of a dataset and a statistical analysis plan for algorithm assessment. The plan must estimate the expected uncertainty of the algorithm assessment results for a range of algorithm performance levels using modeling and simulation.
• Demonstration of the suitability of the proposed tool for use in a regulatory setting (e.g., preclinical assessments of safety, effectiveness, or performance.

Transitioning from Phase I to Phase II Award:

• Activation of phase II award is contingent upon FDA’s acceptance of the MDDT Qualification Plan.

Phase II Milestones must include:

• Engagement with FDA to refine and execute an appropriate strategy for Full MDDT Qualification.
• Optimization of a regulatory/clinical utility and value by testing sufficient number of samples to unequivocally prove statistical significance of the tool in support of its CoU.
• Preparation and submission of a Full Qualification Request Package to the FDA’s MDDT Program. 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.
• Demonstration of the safety and efficacy of the data-driven tool in relevant testing models as required by FDA.
• Approval of MDDT Qualification by FDA.

Gantt charts or other similar graphics may be used for added clarity. These milestones will be the basis for judging progress and the successful completion of the work proposed. Transition to phase II of a study funded under this FOA is contingent upon achievement of milestones.

Medical-Device-Development-Tool (MDDT) Qualification Strategy (Required 2 page limit)

Applications responsive to this FOA must show an understanding of the MDDT qualification process and include well-defined scientific and regulatory justifications for the proposed data-driven tool according to the programmatic and technical milestones. A specific section entitled MDDT Qualification Strategy must describe a technical roadmap for the research and development needed to support the MDDT qualification from FDA. Proposed tools must seek to address specific bottlenecks in medical device development and regulatory evaluation of new DOC biomaterials. Successful completion of FDA’s MDDT Qualification requires Acceptance of a MDDT Qualification Plan and qualification of the MDDT after review of a Full Qualification Package. The Qualification Strategy must provide a detailed description of the following:

• Proposed data-driven tool including purpose, principle of operation, methods of measurement, outputs, etc.

• CoU Statement regarding the feasibility and applicability of the tool.
• Qualification Criteria outlining objective measures for success and scientific justification for the strength of the evidence (quantitative metrics as primary and qualitative metrics as secondary) collected to support qualification and its predictive ability and extent of data-driven tool.
• Scientific justification on how the data collected and the measurement outputs can be correlated to the objective criteria for success.
• Feasibility and usability/applicability of the tool for the stated CoU in the product area of interest.
• MDDT qualification strategy must be mapped to the timelines for Phase I and Phase II activities.

Evaluation Plan (Required 3 page limit)

The filename "Evaluation Plan" should be used to name this attachment. 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. The evaluation plan must align with critical elements needed to support the FDA qualification of the proposed tool according to the stage of tool readiness and evidence plan, which may include information such as: Data Development Plan describing test protocols, methods (experimental, computational, animal, and/or clinical), design verification and validation methods, alternative methods such as human factors. The performance evaluation plan must describe the data to be collected in support of achieving FDA qualification of the MDDT the proposed tool and its CoU. The plan must discuss how performance metrics can be correlated to the Qualification Criteria and demonstrate the feasibility, usability, and overall impact of the proposed tool and CoU

Phase I:

• Develop a pilot dataset that demonstrates how the data will be collected and what it will look like. In addition to truth data (from the clinician, an alternate modality, or patient outcome), include important information about patients and information about the source of the data (site, date, sample prep, chemical formulations, evaluation criteria and testing approaches and protocols, data pre- and post-processing, etc.).
• Develop an algorithm-assessment plan and corresponding software. Use the pilot dataset to demonstrate the algorithm-assessment plan: performance metric, uncertainty estimation, and hypothesis testing. This may require simulation or modeling of the dataset and a hypothetical algorithm. Algorithm-assessment must explore different levels of hypothetical algorithm performance, sources of variability from the algorithm, sources of variability from the dataset, and expected missing data.
• Characterize related uncertainty and account for it in all analyses

Phase II:

Optimize and validate proposed data-driven tool for a given CoU addressing gaps in preclinical characterization and regulatory evaluation of novel dental, oral, and craniofacial biomaterials according to technical specifications and design criteria.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

Specific Aims:

Present separate specific aims to be accomplished for the Phase I and Phase II, clearly labeling each as Phase I Specific Aims and Phase II Specific Aims.

Research Strategy:

Applications responding to this FOA are expected to have preliminary data and comprehensive background materials, including information on existing tools or modules and their corresponding characteristics relevant to the proposed work. Appropriate theoretical justification and hypotheses for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data, as evidence that the proposed project is feasible and well-designed for the intended purpose.

Significance:

• Describe how the proposed data-driven tool will address critical problems affecting R&D cycles that contribute to delays in the regulatory evaluation and translation to human use of novel biomaterials for DOC applications.
• Describe how the project will successfully analyze proposed existing data resources to enhance R&D of biomaterials for DOC applications.
• Describe advanced data-driven technologies and computational material science to advance the forefront in R&D of DOC biomaterials.

• Clearly articulate the significance of the tool from the perspective of its potential CoU.

Investigators:

• Describe the expertise of a dedicated team member who is responsible for communications with FDA MDDT program representatives.

Approach:

The Approach section must have a clear demarcation of the Phase I and Phase II portions of the application and contain elements indicated below, as necessary.

• Explanation of provenance, quality and other relevant characteristics describing datasets selected for the development and testing of data-driven tools for a proposed CoU that addresses specific challenges/bottlenecks in the R&D cycle of biomaterials indicated for DOC applications.
• Description of access to relevant high-quality datasets to be used in the development and performance verification and validation activities of proposed data-driven tools aimed to support a specific CoU in the R&D cycle of biomaterials.
• Explanation of potential impact of scientific advances achieved through the proposed data-driven tool on overall product development and the regulatory evaluation of novel biomaterials.

• Discussion of challenges to be addressed with the data under consideration, why the data may not currently be ready for direct application in the proposed project, ways to improve data and use of the transformed data in proposed approaches and tools.
• Specific information on how the proposed research activities will address the research objectives of this FOA, including how multi-expertise research areas will be integrated and participants interact to achieve a cohesive and innovative research program that will accomplish the objectives.
• Explanation of how the proposed approach addresses a specific bottleneck in the R&D cycle and regulatory evaluation of DOC biomaterials. The application must demonstrate a plan to correlate performance metrics to feasibility, usability, reusability and overall impact of the proposed tool and CoU per FDA’s Qualification Criteria.
• Describe measures and reporting of relevant testing implementation outcomes, to inform future community, local, state, and federal policies.
• Describe how the following are met:

• Intended users must be involved in the design and testing of the approach.
• Solutions must be appropriate to the users in terms of ease of use, understandability and technical sophistication.
• The proposed innovation must deliver benefit to the users.
• Best practices, and relevant FDA guidance and industry standards are adequately leveraged in the proposed software engineering and computational modeling efforts, including, but not limited to: FDA Guidance on General Principles of Software Validation, Draft FDA Guidance on Premarket Submissions for Device Software Functions, and Credible Modeling and Simulation Practices?

• A Data Readiness section must be provided and include the following:

• The origin, quality, characteristics of datasets to be used to support the objectives of the proposed project and the rationale for dataset selection.
• Description of training datasets that are of high quality and well-labeled and structured.
• Describe how the inclusion of different perspectives are accounted for in the membership of development teams and user groups.
• Description of how the diverse features in selected datasets (e.g., demographics, material compositions, experimental test results, etc.) will adequately support the training and validation of the computational tools.
• Description of data standards to be used to ensure all sourced and shared data have appropriate documentation describing method of collection, what the data represent, potential limitations for use, and any other relevant metadata.

• Justification of the data collection sample size to allow adequate training and evaluation of future AI/ML models to generate reliable outcomes
• Strategy to achieve data integration and data harmonization with minimal batch effects and artifacts, especially for longitudinal data or data that grow over time
• Strategy for producing data and model requirements for integrated AI/ML analyses using multiple models when data collection involves multimodal data types from complex systems
• Strategy for incorporating data collection workflows and processes, including machines or human operators as needed
• A plan for data quality control and analysis processes to ensure the completeness of data and metadata, and to minimize data variabilities caused by subject population selection biases and batch effects.

• A Software Development section must be provided and include the following:

• A detailed description of the life cycle development plan of the proposed software system.
• Planning, requirements, traceability, testing, risk assessment, design reviews, change management, and many other aspects of good software engineering are important activities that together help to support a conclusion that software is validated.

Timeline:

• A timeline must be included for both phases. Milestones must be mapped onto this timeline. Applications lacking clearly described timelines for both phases, as well as the Go/No-Go Transition Milestone will be considered incomplete and will not be reviewed.

Letters of support: Letters of support may be included to help demonstrate accessibility to relevant data and the degree of productive multi-domain collaborations through the collection, dissemination, analysis, and interpretation of datasets supporting Phase I and II milestones

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan following instructions in the SF424 (R&R) Application Guide.
• Applications must also include a Data Management Plan describing detailed plans for archival, sharing and long-term preservation of the data or explaining why long-term preservation and access cannot be justified.

Appendix:

Note that Phase I SBIR/STTR Appendix materials are not permitted. Only limited items are allowed in the Appendix of other small business applications. The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide Instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Section 2 - Study Population Characteristics

• While this FOA will not support clinical trials, human subject data may be used to support the training and validation of the proposed data-driven tools. Awardees are expected to include scientifically justified considerations on data selection by sex/gender, race and ethnicity, age and other relevant demographic factors, and to consider intersectionality as appropriate.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and time. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) SBIR/STTR Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Transitioning from Phase-I to Phase-II Award will be contingent on FDA’s approval of the MDDT Qualification Plan (see section part 2, section 1 for details).

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) SBIR/STTR Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIDCR, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIDCR Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The use of specific, quantifiable, scientifically rigorous milestones in phase I and phase II are required towards achieving FDA qualification of the proposed tool as a new MDDT. Reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance the efficiency of biomaterials R&D and facilitate regulatory review in the DOC domain.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field?Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed project have commercial potential to lead to a marketable product, process or service? (In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization?)

Specific to the FOA:

• How well does the proposed data-driven tool address critical problems affecting research and development (R&D) cycles that contribute to delays in the regulatory evaluation and translation to human use of novel biomaterials for DOC applications?
• To what extent does the application convincingly articulate how the project is likely to succeed in analyzing proposed existing data resources to enhance R&D of biomaterials for DOC applications?

• How compelling is the proposed approach towards establishing a data-driven tool that is qualified by FDA as a new MDDT to address a specific CoU in the R&D cycle of DOC biomaterials by the end of the phase II award?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:

• To what extent does the application include dedicated experts in the multidisciplinary team with appropriate knowledge on regulatory considerations on the development of new dental-oral-craniofacial (DOC) biomaterials, data science and data-driven software products who can facilitate communications with FDA’s MDDT Program representatives?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? For a Phase I application, are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

• Evaluate the robustness of the proposed approach to identify and access relevant datasets, as well as to establish data readiness to support computational approaches.

• How comprehensive is the data readiness plan to support identification, access, aggregation, annotation, harmonization, and quality control of relevant data selected for the training and validation of the proposed data-driven/computational modeling efforts? How long will it take? How can we trust the quality of the data used for the computational work?

• Are there dedicated resources to ensure that accurate, consistent, and usable data is accessible for modeling efforts? How accurate, reproducible, and generalizable are the findings reported by the groups who generated the existing resources?
• Evaluate the strengths of the datasets selected for the development and testing of data-driven tools for a proposed context of use (CoU) and the ability to address specific problems in the R&D cycle of biomaterials intended for DOC applications

• Comment on the strengths of the development plan for the proposed software tool. Does the development plan adequately leverage best practices, and relevant FDA guidance and industry standards into the proposed software engineering and computational modeling efforts, including, but not limited to: FDA Guidance on General Principles of Software Validation, Draft FDA Guidance on Premarket Submissions for Device Software Functions, and Credible Modeling and Simulation Practices? Is there sufficient information on distinct modules, layers, and interfaces that comprise the device, their relationships, the data inputs/outputs and flow of data, and how users or external products (including IT infrastructure and peripherals) interact with the system and software. Are traceability, unit and system testing, risk assessment, design reviews, and change management considerations adequately considered?
• Evaluate the strengths of the Data Management Plan in the context of managing the data lifecycle (e.g., archival, processing, sharing and long-term preservation of data) in a manner that is consistent with achieving the goals of this funding announcement.

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangement?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Milestone Plan

Do the milestones described in the Milestone Plan provide a measurable set of events that can be determined as having been met? Are the listed milestones reflective of the work proposed in phase I, and annually for the work proposed in phase II? Do milestones describe a detailed, quantitative, go/on-go criteria for each milestone? Does the Phase I application specify clear, appropriate, measurable goals (milestones) that are achievable prior to initiating Phase II? Does the study timeline adequately account for project milestones and a technical roadmap to achieve the preparation and submission of 1) an MDDT Qualification Plan (phase I) and 2) an MDDT Qualification Request Package (phase II) to FDA? Evaluate if the study timeline is well justified and feasible within the proposed project period.

Qualification Strategy for Medical-Device-Development-Tool (MDDT)

Does the MDDT Qualification Strategy provide a detailed description of the proposed data-driven tool including principle and method of measurements? Is a Context of Use (CoU) Statement included and does it address the feasibility and applicability of the tool? Does the MDDT Qualification Strategy provide the scientific justification on how the data collected and the measurement outputs can be correlated to the objective criteria for success? Is feasibility and usability/applicability of the tool for the stated CoU in the product area of interest addressed? Is the MDDT Qualification Strategy mapped to a timeline across phase I and phase II and is the timeline reasonable and appropriate?

Evaluation Plan

Comment on the strengths of the quantitative and qualitative metrics in providing a clear and concise way to appraise the scientific merit and feasibility of the proposed specific aims. Comment on the degree of alignment of the evaluation plan with critical elements needed to support the MDDT Qualification by FDA of the proposed tool. Evaluate if the plan describes performance metrics that can be correlated to the Qualification Criteria to demonstrate the feasibility, data readiness, usability, reusability and overall impact of the proposed tool and CoU.

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan.

• Specific for this FOA:
  • Potential Market Interest: To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

Phase II Applications

For Phase II Applications, how well did the applicant demonstrate progress toward meeting the Phase I (or Phase I-like) objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

Phase I/Phase II Fast-Track Applications

For Phase I/Phase II Fast-Track Applications, reviewers will consider the following:

1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

2. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Phase IIB Competing Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications with Foreign Components

Reviewers will consider whether work to be performed outside of the United States is thoroughly justified, based on a rare and unique circumstance, and necessary to the overall completion of the project.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by a) appropriate Scientific Review Group convened by NIDCR in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a committee process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications wil be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Dental and Craniofacial Research Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The Office of Inspector General Hotline accepts tips from all sources about potential fraud, waste, abuse and mismanagement in Department of Health & Human Services programs. The reporting individual should indicate that the fraud, waste and/or abuse concerns an SBIR/STTR grant or contract, if relevant. Report Fraud.

Not Applicable

3. Reporting

NIH requires that SBIR/STTR recipients submit the following reports within 120 days of the end of the grant budget period unless the recipient is under an extension. When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

• Final RPPR (requirements have recently changed - please see the NOT-OD-17-085)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR)
• SBIR.gov
• Quarterly reports are due to the Payment Management System 30 days following the end of each calendar quarter.

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

SBA Company Registry (Questions regarding required registration at the SBA Company Registry and for technical questions or issues)
Website to Email: http://sbir.gov/feedback?type=reg

Orlando Lopez, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-402-4243
Email:[email protected]

Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR
Telephone: 301-594-5593
Email: [email protected]

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 45 CFR Part 75 and 2 CFR Part 200.

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), as reauthorized and extended under P.L. 114-328, Section 1834, and P.L. 115-232. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.