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

The National Institutes of Health (NIH)’s issuing this funding opportunity announcement (FOA) in response to the declared public health emergency issued by the Secretary, HHS, for 2019 Novel Coronavirus (COVID-19). This emergency FOA from the NIH provides an expedited funding mechanism as part of the Rapid Acceleration of Diagnostics-Radical (RADx-rad) initiative.

The goal of this RFA is to solicit Direct to Phase II SBIR applications to advance development of novel, non-traditional, safe and effective biosensing and detection approaches to identify the current SARS-CoV-2 virus or other biomarkers of the COVID-19 disease for use in outbreaks of COVID-19, as well as for use in future pandemics resulting from unknown viruses.

The funding for this award is provided from the Paycheck Protection Program and Health Care Enhancement Act, 2020.

BACKGROUND

SARS-CoV-2 is a novel coronavirus that has recently been identified as the causative agent of COVID-19, a respiratory disease that exhibits a wide range of clinical outcomes from asymptomatic and mild disease to severe viral pneumonia, Acute Respiratory Distress Syndrome (ARDS), Multisystem Inflammatory Syndrome in Children (MIS-C), acute kidney injury, thrombotic disorders, and serious cardiac, cerebrovascular and vascular complications. On March 11, the SARS-CoV-2 outbreak was classified as a pandemic by the WHO. Research is an important component of the public health emergency response before, during and after the emergency. The United States Food and Drug Administration (FDA)-authorized COVID-19 diagnostic testing is critical for slowing the spread of the virus and preventing future outbreaks. Thus, there is an urgent public health need for the National Institutes of Health (NIH) to support the development of a variety of approaches to testing.

Expanding the capacity, throughput, and regional placement of existing technologies and accelerating the development of new technologies will contribute significantly to the current national efforts to curb the COVID-19 pandemic. To help meet this need, NIH launched the Rapid Acceleration of Diagnostics (RADx) initiative to speed innovation in the development, commercialization, and implementation of technologies for COVID-19 testing. The RADx initiative is a national call for scientists and organizations to bring forward their innovative ideas for new COVID-19 testing approaches and strategies.

As part of this program, the NIH developed the RADx Radical (RADx-rad) initiative. RADx-rad will support new, or non-traditional applications of existing approaches, to enhance their usability, accessibility, and/or accuracy. RADx-rad will be centrally aligned and coordinated to harmonize the data collection, storage, and management, providing an opportunity to further explore and identify additional approaches to understand this novel virus. Beyond the current crisis, it is anticipated that the technologies advanced through RADx-rad may also be applicable to other, yet unknown, infectious agents.

To centrally align and coordinate RADx-rad projects to harmonize the data collection, storage, and management, the Data Coordination Center (DCC) will be established to serve as the hub in a hub-and spoke organizational framework within the funded RADx-rad research and development projects serving as spokes. In turn, the DCC will serve as a spoke in the larger NIH RADx initiative by providing de-identified data to an NIH-based data hub. NIH expects that all projects funded under this FOA will actively coordinate, collaborate, and share data with the RADx-rad Data Coordinating Center, as allowed, and with considerations under tribal IRB processes, as appropriate. The RADx-rad DCC will provide support and guidance to RADx-rad awardees in the following three areas: (1) Administrative Operations and Logistics, (2) Data Collection, Integration and Sharing, and (3) Data Management and Use. The DCC will develop (and revise as necessary) a framework for standards, metadata and common data elements that apply to all types of data gathered by RADx-rad awardees in order to maximize potential for longitudinal research, integration with other RADx data, and for evaluation of RADx-rad program impact. The DCC will assist awardees in identifying and obtaining data from public sources (e.g., Census data, Area Deprivation Index, etc.), electronic health records (EHR), administrative data, and others as needed. The DCC will coordinate quality control, data curation, and analyses, and provide tools to monitor progress, performance, and use of the curated data. The DCC will create a mechanism to support harmonizing with other large-scale COVID-19 research efforts and will participate in trans-NIH efforts to support scientific collaboration and data-sharing, evaluation of progress towards sustainable infrastructure, partnership and rapid dissemination of RADx findings.

NIH requires that all projects funded under this RFA will actively coordinate, collaborate, and share data with the RADx-rad Data Coordinating Center, as allowed, and with considerations under tribal IRB processes, as appropriate. Researchers applying to this funding opportunity are strongly encouraged to review the Data Coordinating Center (DCC) funding opportunity (RFA-OD-20-019).

• To the extent possible, data acquisition, collection, and curation strategies should be coordinated with the DCC guidance for annotation and benchmarking of data, including obtaining appropriate consent for data sharing and implementation of the schemas proposed under the ABOUT ML effort ( Annotation and benchmarking on understanding and transparency for machine learning lifecycles ; available at https://www.partnershiponai.org/about-ml/).
• In order to maximize progress and successful outcomes, recipients are expected to participate in DCC-organized activities, including regular (e.g., monthly) progress meetings with individual or subsets of awardees, and twice annual meetings with all RADx-rad awardees.

To maximize research and rapidly implement approaches to address the COVID-19 pandemic, comparisons across datasets or studies and data integration are essential to collaboration. Projects funded through this RFA are strongly encouraged to use the following resources as applicable:

• Data Harmonization for Social Determinants of Health via the PhenX Toolkit: Investigators involved in human-subject studies are strongly encouraged to employ a common set of tools and resources that will promote the collection of comparable data on social determinants of health (SDOH) across studies. In particular, studies with human participants should incorporate SDOH measures from the Core and Specialty collections that are available in the Social Determinants of Health Collection of the PhenX Toolkit (www.phenxtoolkit.org).

• A trans-NIH working group is making existing COVID-19 survey items and investigator contact information publicly available through two NIH-supported platforms: the NIH Public Health Emergency and Disaster Research Response (DR2) [https://dr2.nlm.nih.gov/] and the PhenX Toolkit [https://www.phenxtoolkit.org/index.php]. Researchers addressing COVID-19 questions, whether population-based or for clinical research, are strongly encouraged to consider these COVID-19 specific survey item repositories and select existing survey items or protocol modules currently being fielded.

PURPOSE

This RFA solicits Direct to Phase II SBIR applications to advance development of novel, non-traditional, safe and effective biosensing and detection approaches to identify the current SARS-CoV-2 virus or biomarkers of the COVID-19 disease, and/or with potential to address other pandemics from unknown viruses. Biosensing and detection technologies submitted to this initiative should provide reliable associations between biomarkers emanating from skin or the oral cavity to patients with symptomatic and asymptomatic COVID-19. Leveraging the accessibility of human skin and the oral cavity, this FOA seeks 1) to advance novel biosensing technologies that are innovative, safe, and effective, and 2) to implement such technologies into devices with integrated artificial intelligent (AI) systems for the detection, diagnosis, prediction, prognosis and monitoring of COVID-19 in clinical, community and everyday settings.

Biosensing devices are expected to target skin or the oral cavity as sampling sites. Skin biosensing designs must target detection of volatile organic compounds (VOCs, i.e. scents or odors) emanating from skin in passive and noninvasive manner for use at point of care. In addition to VOCs, oral biosensing technologies may target a wealth of biological, chemical and physical biosignatures representative of SARS-CoV-2 virus and/or COVID-19 disease sampled from exhaled breath/droplets, saliva, and tissues in the oral cavity using a variety of detection schemes.

To this end, leveraging dedicated engineering and artificial intelligence systems is required. For skin monitoring, the device can include Electronic-nose (E-nose) technology or Gas Chromatography (GC). Thus, biosensing technologies targeting VOCs emanating from skin or the oral cavity will be referred to as SCENT (Screening for COVID-19 by E-Nose Technology). Oral biosensing devices may consist of technologies that are thoroughly characterized as safe and effective in preclinical studies to conform to and perform in the oral cavity. Non-invasive, real-time, continuous or periodic measurements of VOCs and other biomarkers in breath, droplets, tissues and other samples emanating from the oral cavity as signatures of onset, progression, and resolution of COVID-19 are desirable.

This FOA expects multidisciplinary collaborations to ensure project success. Disciplines may include: Biomedical engineers, material scientists, biosensing experts, software engineers, chemists, dentists, clinicians, virologists, clinical trialists, biostatisticians, data analysts and other relevant experts in academia and industry.

SPECIFIC RESEARCH OBJECTIVES

SCENT and Oral Cavity Biosensing: With the tentative opening of many States came an increase in COVID-19 cases, thus, there is a critical need for non-traditional testing technologies that are non-invasive, not reagent intensive, and that do not take a long time to gather results. It is highly desirable for an accurate and sensitive system that can provide results in real time and is mobile/portable and deployable in any clinical, community and everyday setting. Current testing technologies are not practical for field use, requiring expensive reagents and enzymes and laboratories certified for potentially virulent samples. These tests are cumbersome to perform because they use aqueous solutions, require multiple steps and hours, if not days, to get results. The SCENT device is envisioned to be used in a hospital, clinic setting, community or even home and workplace. For example, instead of taking temperatures at entrances to establishments, SCENT can be used for more informative and accurate data. The danger of contamination is minimal as SCENT will probe the skin with minimal to no potential exposure to the virus. In addition, the key substrate for SCENT will be VOCs, i.e., scents or odors emanating through skin, which are easier to standardize with, at least, two ways to account for person-to-person differences in skin permeability, namely Total Evaporative Water Loss (TEWL) or skin impedance.

The oral cavity provides another alternative for SCENT VOC detection because it is readily accessible. For example, exhaled breath could be captured and analyzed for direct detection of the respiratory tract infection from unique volatile organic metabolite byproducts of SARS-CoV2 infection.

VOCs from skin and oral cavity offer opportunities for continuous (i.e., wearable) or periodic monitoring of viral infection and disease presentation. The recent advances in biosensing, micro-electromechanical systems (MEMS) and nanotechnology combined with artificial neural networks, artificial intelligence (AI)/machine learning and smart phone technologies could make such a portable, multifunction device a reality. The innovation/challenge is to combine these technologies into devices that measure VOCs on skin and/or oral cavity, subsequently correlating those VOC patterns with COVID-19 signatures through AI/machine learning.

In the current COVID-19 epidemic, this quick screening device would enable doctors to detect and diagnose COVID-19 symptomatic and asymptomatic individuals leading to appropriate treatment and/or quarantine procedures. Additionally, a SCENT platform may be able to differentiate between COVID-negative and COVID-positive-asymptomatic subjects. At the London School of Hygiene and Tropical Diseases, dogs are being trained to detect the scent of potential COVID-19 patients. This is possible because the dog’s olfactory system contains 300 million receptors whereas the human nose has only 5 million receptors. The central premise of SCENT-based devices is their ability to mimic the biological sense of smell with a more robust, standardized and mechanized electronic nose. For example, unique VOC skin signatures are already identified in symptomatic and asymptomatic malarial infections vs. uninfected cases. In the long run, the SCENT platforms are not limited to COVID-19 diagnosis, and can be readily adapted to other pandemics, as well as for the detection of other diseases and conditions. The potential is limited only by the development and availability of the training and validation data sets for VOC signatures that will be used for the machine learning competency.

In addition to VOC detection, the oral cavity provides unique opportunities to enhance virus testing capacity by developing new ways to collect and measure samples for rapid and accurate detection of a wide range of host-specific biomarkers that characterize manifestations of COVID-19 according to reliable biologic, physical and chemical responses. Such biomarkers may be predictive of the severity of the disease, its co-morbidities and its progression and outcome. A variety of existing and emerging biosensing technologies can leverage available analytical methods to develop new diagnostic strategies by restructuring their sensing module for the detection of biomolecules, especially nano-sized objects such as protein biomarkers and viruses. Current sensing platforms for SARS-CoV-2 may require continuous updates to address growing challenges in the diagnosis of COVID-19 as the virus could change and spread largely from person-to-person, indicating the urgency of early diagnosis. Oral biosensing technologies may include several major functional modules optimized for COVID-19 detection, such as: 1) sensing bioreceptor; 2) transducer; 3) detector with readout for visual display; and 4) secure integration of interoperable features with accessory clinical internet-of-things (IoT) systems and digital platforms. It is highly desirable that Quality by Design (QbD) principles, and available crowdsourced data on the SARS-CoV-2 virus and COVID-19 disease, are leveraged in early research and development of oral biosensing technologies to employ a holistic strategy that accounts for possible end-state manufacturing, production, and usability milestones. Rather than relying on finished product testing alone, leveraging early identification of critical product attributes and process parameters to drive preclinical development will increase the likelihood of success in meeting clinical performance requirements with cost-effective scalability and deployability.

Specific approaches of interest for oral biosensing may include, but are not limited to:

• Develop and optimize novel oral biosensors using various methods of detection mechanisms, such as: optical, electrochemical, piezoelectric, magnetic, micromechanical, thermal, acoustic, and others. For example, imaging approaches for label-free, or smart-targeted exogenous, contrast for localized detection of COVID-19 specific biomarkers in the oral cavity, or oral intradermal mucosal patches to detect local and systemic infection levels to facilitate identification of new early stage diagnostic sentinels. Changes in the lips and oral cavity environment, such as blood supply, oxygenation, inflammatory and immune response, sense of taste, volatile metabolites and other presentations could be monitored.
• Integrate oral biosensors into a variety of form factor designs and configurations (disposable vs multi-use) suited for health/dental care environments and at home-use, including toothbrushes, dental instruments, and appliances (e.g. orthodontic brackets, crowns, dental implants, mouthguards) for detection, monitoring, and diagnosis of COVID-19. These integrated oral biosensors could be optimized not only to detect traditional biomarkers (virus and antibody), but also for additional biomolecular signatures predictive of COVID-19 disease onset, progression and resolution.
• Integrate and ensure interoperability with RFID enabled technologies, blockchain, artificial intelligence, and machine learning systems for automatic detection, secured data exchange, and provenance and traceability controls for disease tracking across multiple data streams. Ensure compatibility of test readouts with crowdsourcing Apps to add power to worldwide data pool to more effectively track the infection and symptoms and accelerate translational research.

SCENT and Oral Biosensing Technologies Product Development Plans:

Product development plans should conform to an aggressive RADx-rad program timeline without sacrificing expected performance milestones on safety or effectiveness. Adoption of Rapid Prototyping, Agile Methodologies and Quality by Design (QbD) principles are highly encouraged to advance projects with demonstrated early stage feasibility to late stage preclinical development of SCENT and oral biosensing platforms towards relevant FDA certifications/approvals. A holistic strategy that accounts for end-state manufacturing, production, and usability is expected. Early identification of critical product attributes (e.g., comparable accuracy with the current standard, safety, portability, etc.) and process parameters (e.g., ruggedness of materials used in the device, but also built-in process analytical technologies to ensure acceptable device function) are required. Design of experiment (DoE) techniques are essential. These preclinical development strategies will increase the likelihood of success in meeting eventual clinical performance requirements. It is envisioned that these technologies will complement traditional virus and antibody detection to monitor the onset, progression, and resolution of COVID-19.

Applicants are strongly encouraged to use a systems approach to product development and preclinical performance testing of the proposed device to establish a robust proof-of-concept feasibility towards possible FDA certification/approval and/or product commercialization.

Assembly and integration of the prototype SCENT and Oral Biosensing platforms: The SCENT platform should comprise (1) a Volatile Organic Compound (VOC) sampler; (2A) an electronic nose or (2B) a gas chromatographic (GC) column; (3) an appropriate detector, (4) AI/Machine Learning capabilities to distinguish VOC skin signatures across many levels of COVID-19 infection for accurate diagnosis, and (5) an intuitive, user-friendly interface. Assembly of the hardware and software for either the E-nose or GC prototypes from off-the-shelf components is encouraged to expedite development.

The VOC skin sampler can be a simple cup where the VOCs emanating from skin are delivered to the e-Nose or GC column via nitrogen gas or other nonreactive gas, or it can be slightly more sophisticated as in solid-phase microextraction (SPME) where the gases are adsorbed on a material and desorbed into the e-Nose or GC column. The skin VOC sampling system will be developed through testing and optimization of potential designs preferably by Design of Experiments (DoE). The sampling system(s) will have to be validated against known mixtures of VOCs with and without in vitro skin models. Other novel skin sampling designs are encouraged.

For the oral cavity sampler, the oral environment presents specific design and performance requirements for VOC sampling that need to be addressed. Therefore, a system’s engineering approach should address major challenges imposed by the oral environment including, varying pH levels and temperatures, oral flora, adhesion to wet intraoral tissues, and material biocompatibility/biofouling.

The sampler for VOCs in the oral cavity can be a blow tube for breath and/or particulates/droplets. However, prevention of infection/contamination of the healthcare worker must be built-in into the design. The sampler can also be an oral probe (analogous to an oral thermometer) placed in contact with oral tissues (e.g., under the tongue) to collect VOCs emanating to the tissue surface. Alternatively, VOCs can be collected from the head space of saliva collected in a closed container. This is a standard procedure that has been applied to VOC analysis of urine. As in the skin sampler, other novel sampling designs for the oral cavity are encouraged.

The E-Nose is generally an array of a number of materials including conducting polymers, quartz crystal microbalances, fluorescence sensors, semi-conducting metal oxides, etc. The collective signals are processed in an artificial neural network and pattern recognition software. For GC the detector can be a mass spectrometer (MS) or flame ionization detector (FID). Identification of the VOC components by comparison to an MS data base is desirable; however, the pattern recognition is more important. Deposition of data/learning sets into the DCC is required.

The portable E-nose or GC instrumentation and detector/s will be integrated with the VOC sampler. For off-the-shelf components, compatibility of software should be considered even before assembly of the SCENT platform. The prototype has to be validated against the current standard, laboratory-grade, commercially-available GC or E-nose instrumentation (e.g., MEMS, etc.) and tested for sensitivity and accuracy against known mixtures of VOCs.

Quality by Design (QbD) and incorporation of process analytical technologies (PATs) are required and must be prominently described in the application. QbD will allow for ease and precision of future manufacturability and ensure that device to device differences are at a minimum, while adverse events that are of device origin are limited. Process analytical technologies are required for accuracy and precision of measurements between devices and between patients. PATs for devices may include standard VOC mixtures, pressure sensors, etc. PATs for patient to patient standardization must include skin temperature sensors, skin permeability sensors (e.g., Transepidermal Water Loss [TEWL], skin impedance, etc.) or skin stiffness among others, that can affect the quantity (and perhaps quality) of VOCs sensed by the detectors.

Adoption of human-factors-engineering and usability-engineering principles must be considered during the development process. This includes usability criteria such as comfort to ensure user acceptance and compliance.

Additionally, VOC sensing approaches for COVID-19 must incorporate design specifications and performance criteria for risk mitigation of potential measurement interferents including, but not limited to: metabolites produced in pathological conditions other than COVID-19; compounds introduced during patient treatment such as drugs, plasma expanders, and anticoagulants; substances ingested by the patient such as alcohol or nutritional supplements. Lastly, the proposed approaches should address other potential causes of examination (analytical) interference, such as: chemical, physical and detection artifacts; non-selectivity and non-specificity of detection; and other sources of error that might affect COVID-19 diagnostics. Risk mitigation and alternative methods are expected.

Most of the technological components required to build these sensing platforms are already developed and used for other purposes. The innovation in this initiative will be in bringing together the expertise and capabilities in these technologies and coupling them with clinical and infectious disease expertise to develop an integrative noninvasive device that will be used specifically for the diagnosis of COVID-19. Future applications of SCENT have potential for monitoring of overall health and detection of other diseases and will be a consideration but not required. The metrics/requirements for successful SCENT are accuracy, sensitivity and selectivity comparable to or exceed current standard, FDA-approved COVID-19 diagnostics. Portability, accessibility, and affordability are also key considerations for SCENT and oral biosensing.

Since SCENT and oral biodevices can potentially have global applicability and use, it must follow the principles of ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable to end users) criteria, outlined by the World Health Organization (WHO), which provides a good framework for evaluating point of care devices specially for resource-limited environments.

Software and Integrated Systems Development: Software systems and algorithms used in testing protocols from biomarker sampling (e.g., VOCs, biomolecules, antibodies, etc) to analysis will be developed and tested for smooth, error-free operation of the device. A robust performance testing plan must be established to ensure verification and validation of compatibility and integration between proposed biosensing technologies with other off-the-shelf hardware and software components sourced from different manufacturers at a unit and systems level.

Use of commercially available pattern-recognition and machine learning software is allowed and even encouraged to facilitate agile and rapid development. The sensitivity and accuracy of the software must be verified and validated on surrogate samples. In addition, reference/training and validation sets from actual clinical samples will be used to show proof of principle of the machine learning algorithm.

Testing SCENT and Oral Biosensing Prototypes: This initiative requires that the preclininical performance of proposed novel biosensing technologies is tested to ensure human safety and effectiveness according to recognized industry standards and relevant FDA regulatory considerations. Product development plans may include: preclinical performance testing utilizing benchtop evaluation, animal models and human tissue samples; design validation in actual or simulated use with test subjects; comparative experiments against gold standard molecular methods; usability evaluations with clinicians, patients and other end users; and secondary analysis of physiologic data and metadata from existing clinical studies. As appropriate, performance evaluations should consider relevant testing of individual biodevice components and integrated systems with respect to biocompatibility, biofouling, shelf-life, sterility assurance, mechanical and structural integrity, electromagnetic compatibility, electrical safety, usability/operability, wireless data transmission, battery safety and life-time, data security and privacy, and any other criteria needed to support the targeted clinical application. Requirements for rapid analysis are driven by the stability and selectivity of biomarkers for detection by biosensor systems. As appropriate, innovation of verifiable biomarkers, creative use of nanotechnology and other functionalization approaches should be considered to improve the analytical performance of biosensors for specific and sensitive detection characteristics needed for point-of-care diagnostics. Usability criteria such as comfort, discreetness, and absence of interference with daily functions must be considered to ensure user acceptance and compliance.

For patient testing, data training sets must be collected on known (1) COVID-19 positive, symptomatic, (2) COVID-19 positive, asymptomatic and (3) COVID-19 negative subjects as determined by the current standard FDA approved method. A statistically significant number of patients with known condition(s) are expected to be tested for confident delineation of (1), (2) and (3) based on training sets and comparable accuracy to FDA-approved COVID-19 diagnostics. NCATS Clinical and Translational Science Awards (CTSA) hubs can be used in the clinical validation for recruitment and trial implementation.

Evaluation Plan: Projects must include an evaluation plan demonstrating how the proposed COVID-19 diagnostic strategies/activities will be assessed safety, effectiveness and impact . Identification of appropriate risk mitigation strategies and alternative methods is expected. Since SCENT and oral biodevices can potentially have global applicability and use, the principles of ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable to end users) criteria, outlined by the World Health Organization (WHO), should be considered as framework for evaluating point of care devices specially for resource-limited environments.

Leveraging Existing Research Resources:

Applicants are also strongly encouraged to leverage existing research resources for their studies whenever possible. NIH has developed innovative solutions that will improve the efficiency, quality, and impact of the process for turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public through programs such as: NCATS Clinical and Translational Science Awards (CTSA) Program, Research Evaluation and Commercialization Hubs (REACH), Small Business Education and Entrepreneurial Development (SEED), Commercialization Accelerator Program (CAP) for assistance in proof of concept and commercialization of a marketable product. Applicants are encouraged to leverage all available internal (e.g., home institutional) and external (e.g., external institutional, NIH, and/or NIDCR and NCATS) resources to identify clinically relevant COVID-19 patient populations.

Regulatory Approval Plan: A plan for the regulatory approval of technologies, tests and approaches must be developed based on the data generated from the research objectives. The plan should be aligned with relevant regulatory requirements for the technology and describe foreseeable regulatory risks that could impact the technology development. The plan must also describe how the technology would fit with current standard of care.

Milestone Plan: All projects will be milestone-driven towards late-stage preclinical development and potential commercialization of the proposed technologies based on clear go/no-go criteria that are quantifiable. Applicants must include a Milestone Plan.

Prior to funding an application, the Program Official will contact the applicant to discuss the proposed project milestones and any changes suggested by NIH staff or the NIH review panel. The Program Official and the applicant will negotiate and agree on a final set of approved project milestones which will be specified in the Notice of Award. These milestones will be the basis for judging progress and the successful completion of the work proposed.

See https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library/Devices-Milestones for an example of milestones. NOTE: These are suggested formats only and should be adapted as appropriate.

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 Phase III Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including NIH, SBIR/STTR Programs are implementing the Phase II to Phase III 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.

Information on the Phase II to Phase III 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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM, SBA Company registry, and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.In the case of Emergency awards, if the applicant is unable to comply with the requirement to complete and maintain SAM registration at the time of application submission, contact the agency immediately.
• 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 DUNS number to complete this registration. SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
• eRA Commons - Applicants must have an active DUNS number number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

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. 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 (see NOT-OD-11-101).

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 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.

A small business concern may subcontract a portion of its SBIR or STTR award to a Federal laboratory within the limits above. A Federal laboratory, as defined in 15 U.S.C. 3703, means any laboratory, any federally funded research and development center, or any center established under 15 U.S.C. 3705 & 3707 that is owned, leased, or otherwise used by a Federal agency and funded by the Federal Government, whether operated by the Government or by a contractor.

The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of 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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

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:

Orlando Lopez, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-402-4243
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.

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, with the following additional instructions:

Research Strategy:

It is highly desirable that Quality by Design (QbD) principles, and available data on the SARS-CoV-2 virus and COVID-19 disease, are leveraged in early research and development of SCENT and oral biosensing technologies to employ a holistic strategy that accounts for possible end-state manufacturing, production, and usability milestones.

Approach

Applications should include scientifically sound approaches to preclinical product development driven by specific clinical needs and detailing relevant milestones to establish preclinical safety and effectiveness performance in support of anticipated regulatory requirements.

Evaluation Plan: Projects must include an evaluation plan demonstrating how the proposed COVID-19 diagnostic strategies/activities will be assessed for safety, effectiveness and impact. Identification of appropriate risk mitigation strategies and alternative methods is expected.

Regulatory Approval Plan: A plan for the regulatory approval of technologies, tests and approaches must be developed based on the data generated from the research objectives. The plan should be aligned with relevant regulatory requirements for the technology and describe foreseeable regulatory risks that could impact the technology development. The plan must also describe how the technology would fit with current standard of care.

Milestone Plan: All projects will be milestone-driven towards late-stage preclinical development and potential commercialization of the proposed technologies based on clear go/no-go criteria that are quantifiable. Applicants must include a Milestone Plan that includes:

• Detailed, quantitative, go/on-go criteria for each milestone. Quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in internal review but also in consideration of the awarded project for funding of non-competing award years.
• Detailed timelines (e.g. Gantt chart) for the anticipated attainment of each milestone and the overall project goals.
• Any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.
• Additionally, feasible and appropriate plans to submit data, data collection instruments, and outcomes/products to the DCC should be included in the milestones. The applicant must acknowledge that they will include testing implementation outcomes in their reporting to the DCC, to inform future community, local, state, and federal policies.

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 data must be deposited into the RADx-rad Data Coordination Center (RFA-OD-20-019)

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan.

Appendix:

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.

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

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.

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.

Pre-award costs may be incurred from January 20, 2020 through the public health emergency period and prior to the date of the federal award.

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 Component of the SF424(R&R) Application Package. 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 DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) SBIR/STTR 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. Projects that do not have an infrastructure to rapidly report study findings and impact to the DCC will not be reviewed. Projects that propose discovery research to identify new biomarkers will not be reviewed.

In order to expedite review, applicants are requested to notify[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.

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: Does the proposed research fit within the mission of an emergency response to provide critical expertise, resources or activities? Will successful completion of the aims contribute to public health efforts for the control of SARS-CoV-2 (COVID-19) infection and related pathogenic processes? Will the technologies proposed result in noninvasive, reliable, and reproducible COVID-19 tests? Is there a clear characterization of the benefit (e.g., exponential or incremental, faster, smaller, cheaper, easier, safer, more effective, more accurate)?

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 the FOA: Are the PD/PIs, collaborators, and other researchers well suited and appropriate to carry out the project? Have the research team members demonstrated an ongoing record of accomplishment in the development of VOC analytical technologies? Does the team also include appropriate expertise in AI/machine learning, virology, skin and oral cavity physiology?

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?

Specific to the FOA: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Is the emergency time frame feasible for the proposed research? Will the expected results lead to advances in technologies used in the diagnosis and treatment of human diseases? Has the applicant described an expected regulatory pathway? Does the applicant adequately describe how the technology would fit with current physician/dentist practice/standard of care? Does theevaluation plan demonstrate a clear plan for how the proposed COVID-19 diagnostic technology will be assessed for effectiveness?

Data Coordination Plan: How feasible and appropriate are the plans to submit data, data collection instruments, and outcomes/products to the DCC?

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?

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:

• • Are milestones timely and robust and associated with clear, quantitative criteria for efficacy and success that allow go/no-go decisions?
  • Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
  • Are there additional key experiments that need to have milestones?
  • Does the provided Gantt chart demonstrate a reasonable timeline for the project plan?

Data Sharing Plan: Is the data sharing plan adequetly described?

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.

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).

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) Sharing Model Organisms and (2) Genomic Data Sharing Plan.

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 an appropriate internal review panel convened by NCATS and NIDCR staff, using the stated review criteria in the FOA.

As part of the scientific review, all 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 review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. 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

Refer to Part 1 for dates for 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

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 grantee’s business official.

Awardees 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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please 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. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. 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.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please 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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

NIH is requiring data sharing for all COVID-19 projects, where it is not prohibited (i.e., Tribal data sovereignty). The NIH expects and supports the timely release and sharing of final research data from NIH-supported studies for use by other researchers to expedite the translation of research results into knowledge, products, and procedures to improve human health. Grantees are expected to work with the RADx-rad DCC to submit common evaluation metrics on COVID-19 testing-related outcomes and implementation to the DCC. Grantees should identify a dedicated unit responsible for these data reporting activities. NIH expects that all projects funded under this FOA will actively coordinate, collaborate, and share data with the RADx-rad DCC, as allowed, and with considerations under tribal IRB processes, as appropriate. Researchers applying to this funding opportunity are strongly encouraged to review the DCC funding opportunity. To the extent possible, data acquisition, collection, and curation strategies should be coordinated with the DCC guidance for annotation and benchmarking of data, including obtaining appropriate consent for data sharing and implementation of the schemas proposed under the ABOUT ML effort ( Annotation and benchmarking on understanding and transparency for machine learning lifecycles ; available at https://www.partnershiponai.org/about-ml/). Grantees are expected to participate in DCC-organized activities, including regular (e.g., monthly) progress meetings with individual or subsets of awardees, and twice annual meetings with all RADx-rad awardees.

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 grantees submit the following reports within 120 days of the end of the grant budget period unless the grantee is under an extension. When multiple years are involved, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Funds awarded using appropriations provided by the Paycheck Protection Program and Health Care Enhancement Act, Public Law 116-139 will be issued in unique subaccounts in the HHS Payment Management System and will require separate financial reporting from any other funds awarded.

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: 301-945-7573

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, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-402-4243
Email: [email protected]

Danilo Tagle, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-8064
Email:[email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

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 42 CFR Part 52 and 45 CFR Part 75.

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.