SBIR

PHS 2020-2 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required)

Background The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, also known as America's Seed Fund, are one of the largest sources of early-stage capital for technology commercialization in the United States. These programs enable US-owned and operated small businesses to conduct research and development that has a strong potential for commercialization. National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) support small businesses through the SBIR and STTR programs to translate promising technologies and products to the private sector that align with their mission to improve health and save lives. The SBIR program, as established by law and reauthorized under Public Law 114-328, Section 1834 and Public Law 115-232, is intended to meet the following goals: stimulate technological innovation in the private sector; strengthen the role of small business in meeting federal research and development needs; increase the private sector commercialization of innovations developed through federal research and development funding; foster and encourage participation in innovation and entrepreneurship by women and socially or economically disadvantaged persons. In addition, the STTR program aims to foster technology transfer through cooperative research and development between small businesses and research institutions. Federal agencies with extramural research budgets over $100 million are required to set-aside 3.2% of their budget to SBIR, and those with research budgets over $1 billion are required to set aside 0.45% of funds for STTR. The SBIR/STTR program is a phased program. The main objective in SBIR/STTR Phase I is to establish the technical merit and feasibility of the proposed research and development efforts, whereas in SBIR/STTR Phase II it is to continue the R&D efforts to advance the technology toward ultimate commercialization. An objective of the SBIR and STTR programs is to increase private sector commercialization of innovations derived from federally supported research and development. At the conclusion of an SBIR/STTR Phase II, it is expected that the small business will fully commercialize their product or technology using non-SBIR/STTR funds (either federal or non-federal). Purpose This Funding Opportunity Announcement (FOA) issued by the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) invites eligible United States small business concerns (SBCs) to submit Small Business Innovation Research (SBIR) Phase I, Phase II, Direct to Phase II (NIH Only), Fast-Track (NIH only), and Phase IIB (NIH only) grant applications. Small business applicants interested in submitting an STTR grant application should submit to PA-20-261 or PA-20-265. NIH Fast-Track: An NIH SBIR Fast-Track incorporates a submission and review process in which both Phase I and Phase II applications are submitted and reviewed together as one application to reduce or eliminate the funding gap between phases. NIH Direct to Phase II: For small businesses that have already demonstrated scientific and technical merit and feasibility but have not received a Phase I SBIR or STTR for that project, NIH can issue a Direct to Phase II award. The NIH Direct to Phase II will accept Phase II submissions regardless of the funding source for the proof of principle work on which the proposed Phase II research is based. Small businesses that are eligible to submit Phase II applications for projects that were supported with a Phase I SBIR or STTR award are expected to submit the regular Phase II application as a "Renewal" application based on the awarded Phase I SBIR or STTR project. Only one Phase II application may be awarded for a specific project supported by a Phase I award. NIH Phase IIB: Some projects initiated with SBIR or STTR funding require considerable financing beyond the SBIR and STTR Phase II to achieve commercialization. NIH Institutes and Centers (ICs) may allow small businesses who have been awarded a Phase II SBIR or STTR to submit a Phase IIB (second, sequential Phase II) SBIR application that will provide additional funding for Phase II SBIR or STTR projects. These renewals are typically offered for those projects that require extraordinary time and effort, including those requiring regulatory approval or developing complex instrumentation, clinical research tools, and behavioral interventions. Commercial potential (i.e. the probability that an application will result in a commercial product) will be a strongly considered in review (refer to Section V. Application Review Information) and making funding decisions. Applicants are encouraged to secure substantial independent third-part investor funds (i.e., third-party funds that equal or exceed the requested NIH funds). An applicant's ability to secure substantial independent third-party investor funds will help validate the commercial potential of the proposed SBIR Phase IIB project. Examples of third-party investors include, but are not limited to, another company, a venture capital firm, an angel investor, a foundation, a university, a research institution, or a State or local government, or any combination of the above. Applicants should provide a commercialization plan that describes the long-term commercialization strategy and details on any independent third-party investor funding that has already been secured or will be provided during the Phase IIB project period. If applicable, the application should include letters of support from third-party investors. NIH ICs that accept Phase IIB applications, either through this SBIR FOA or other specific FOAs, are listed in the PHS 2020-2 SBIR/STTR Program Descriptions and Research Topics for NIH, CDC, and FDA. Additional requirements and instructions (e.g., submission of a letter of intent) are available in the specific IC research topics section and in the NIH Targeted Funding Opportunities that allow Phase IIB applications. Specific Objectives The PHS 2020-2 SBIR/STTR Program Descriptions and Research Topics for NIH, CDC, and FDA represent scientific program areas that may be of interest to applicant small businesses in the development of projects that have potential for commercialization. Small business concerns that have the research capabilities and technological expertise to contribute to the R&D mission(s) of the NIH, CDC, or FDA awarding components identified in this FOA are encouraged to submit SBIR grant applications in these areas. SBIR grant applications will also be accepted and considered in any area within the mission of the Components of Participating Organizations listed for this FOA. In addition to the general SBIR solicitations, some awarding components have additional, specific NIH Targeted Funding Opportunities of potential interest to small businesses. Applicants are not required to identify a potential awarding component prior to submission of the application but may request one on the Assignment Request Form. Staff within the NIH’s Center for Scientific Review (CSR) office, the single receiving point for all NIH, CDC, and FDA grant applications, will assign all applications to the most appropriate Agency and Institute/Center (IC) based on their mission and the science proposed. For specific information about the mission of each NIH IC, visit the List of NIH Institutes, Centers, and Offices website. All applications submitted to this Parent Funding Opportunity Announcement must propose clinical trial(s). SBIR applications that do not propose clinical trial(s) should be submitted to PA-20-260. Applicants should note that some ICs only accept applications proposing mechanistic studies through this funding opportunity announcement and are noted in the PHS 2020-2 SBIR/STTR Program Descriptions and Research Topics for NIH, CDC, and FDA. A mechanistic study is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention. If the proposed research project includes clinical trial other than a mechanistic study that would be assigned to one of these ICs, applicants are advised to contact relevant Scientific/Research staff to discuss alternative mechanisms of support of these studies. Further information about the SBIR and STTR programs can be found at https://sbir.nih.gov/. Frequently asked questions are available to assist applicants and can answer many basic questions about the program.

Support for Small Business Innovation Research (SBIR) to Development and Testing of New Technologies and Bioengineering Solutions for the Advancement of Cell Replacement Therapies for Type 1 Diabetes (R43/R44 Clinical Trial Not Allowed)

Purpose and Research Objectives: Despite clear progress made during the last 15 years on cellular transplantation for T1D, the most recent results demonstrate a long-term limited viability of engrafted islets and, as a result, limited insulin independence under different novel modalities of immunosuppressive (IS) regimens tested. In addition, even the most innovative IS regimens required for transplant survival still have significant immediate side effects and long-term safety is uncertain. These problems together with the scarcity of donor organs and the complexity of transplants mandates a renewed emphasis on the investigation of novel methods within the field of tissue engineering for the development of a bio-artificial, cell-based hormone replacement therapy that may minimize the need of IS. To support this, it is necessary to develop/optimize novel/smart/safe biomaterials, scaffolds, bio-matrices and bio-barriers that may protect grafted cells from immune rejection and simultaneously promote appropriate vascularization/innervation with an efficient exchange of nutrients to optimize cellular long-term survival and proper function. It is also necessary to investigate methods to use different cell sources including human progenitor cells and induced pluripotent stem cells as a valid option for cell replacement therapy. Also, further research on the potential use of xenogeneic cells/islets is needed. Recent advances in this field, because of support by NIDDK/NIH and other funding agencies, demonstrate feasibility of these technologies, mainly in rodent pre-clinical models of T1D. However, important obstacles remain before long-term preclinical efficacy in non-human primates (NHP) and human clinical feasibility may be verified. Examples of areas that need further emphasis/development are: Development of encapsulation systems able to satisfy GMP standards and regulatory agency specifications including strict assurance of sterility, avoidance of bioburden, safety, and reproducibility of a product with adequate quality control measures during manufacture thus making these systems suitable for the clinical application of encapsulated islet technologies. System characteristics may also include: consistency, uniformity and mono-dispersity of hydrogels, defined number of islets per capsule, limited batch to batch variability, complete and gentle encapsulation, minimized time of islets out of culture and scalability. Development of tools and methods for less invasive approaches for implantation of devices Development and optimization of novel biomaterials: highly biocompatible, stable, inert, and of a sufficient porosity to not interfere with the encapsulated cell's physiological regulatory response to stimuli in a NHP and/or human environment. Optimization of longer-term culture and long-term storage methods to improve access to islet cells replacement/transplantation interventions. Optimization of high-throughput screening for selection of suitable implantable device materials. Novel methods to test the in vivo biocompatibility of transplanted capsules/devices and the cell preparations. Generation of biomaterial layers with a bioactive surface capable of actively altering the localized implant environment. Study feasibility of pre-vascularization of devices before implantation to ensure better cell viability and function. Agents incorporated in implantable devices to enhance vascularization at the tissue/device interface during the healing process after implantation. Novel methods/technologies to ensure proper and efficient long-term oxygenation and nutrient delivery to maintain high viability and function of the implanted islets/cells in vivo. Efficient incorporation of oxygen carrying/generating agents to biomaterials/micro-nano devices. Characterization of oxygenation, viability and potency of islets or human stem cell derived (beta-cells/islets) within encapsulation devices in vitro and/or in vivo. Non-invasive assessment of pO2 within devices and at transplant sites – at multiple time points prior to and post-transplant (hours/days/weeks/years). Non-invasive evaluation of cell viability and function within encapsulation devices in vitro and in vitro (e.g., imaging technologies for this purpose). Devise better standardization methods to rapidly and accurately define viability and functional quality of donor islets and human stem cell-derived beta cells/islets. Novel biomimetic and immuno-engineering strategies for the development of immune evasive biomaterials/devices effective in an NHP/human environment with no need of systemic immunosuppression. Bio-immuno-engineering of islets/cells in order to make them resistant to allo/autoimmune rejection without the need of systemic immunosuppression Elucidation of factors/mechanisms that lead to islet exhaustion and potential interventions to ensure islets' functional capacity. Development of devices/technologies to facilitate islets implantation in extrahepatic sites including factors that may facilitate functional long-term intraperitoneal implantation. Optimized methods for storage and shipment of cells/devices for transplantation. Methods/technologies to improve feasibility of using engineered beta/islet cells, such as human progenitor cells and induced pluripotent stem cells, as sources for T1D cell replacement therapy able to induce long-term graft acceptance/tolerance. Development of techniques to maintain and expand human islets and physiologically responsive insulin-producing cells derived from stem/progenitor cells to make them suitable for cell replacement and disease modeling. Development of protocols for standardization of cell sources as reagents - pig cells, human stem cell derived progenitors and functional beta-like cells/islets/preps. Novel in vitro and in vivo pre-clinical disease models such as biomimetic/humanized that may better predict human responses to cells and material/devices. Non-invasive assessment of vascularization and blood flow around implanted encapsulation devices, especially in conjunction with functional (oxygen) measurements.

BRAIN Initiative: Development Optimization, and Validation of Novel Tools and Technologies for Neuroscience Research (SBIR) (R43/R44 - Clinical Trial Not Allowed)

Background

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is a Presidential project aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, shows how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to identify, treat, cure, and even prevent brain disorders.

NIH is one of several federal agencies involved in the BRAIN Initiative. Planning for the NIH component of the BRAIN initiative is guided by the long-term scientific plan, "BRAIN 2025: A Scientific Vision," which details seven high-priority research areas and calls for a sustained federal commitment of $4.5 billion over 12 years. This report can be found at http://braininitiative.nih.gov/. This FOA and other FOAs issued in Fiscal Year 2018 are based on NIH's careful consideration of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group.


In addition to the National BRAIN initiative, the NIH continues to have a substantial annual investment in neuroscience research and in technology development, including through the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. 

Research Objectives

Based on the priority areas identified by the BRAIN 2025, and in further evaluation of the neurotechnologies currently available to neuroscience researchers, it was determined that there is a need to enable broad dissemination of tools/technologies that improve our understanding of brain function. Many of these inventions require additional research and development (R&D) before they can be disseminated to the broader neuroscience community. To fill this research gap, this Funding Opportunity Announcement (FOA) which uses the STTR grant mechanism, will support to support the development of novel neuroscience tools and technologies in order to better understand the structure and function of brain circuits- a major goal of the BRAIN Initiative. This FOA will support further development of neurotechnologies developed through the BRAIN initiative or through other funding programs in preparation for commercial dissemination.

It is expected that the activities proposed will require partnerships and close collaboration between the original developers of these technologies and Small Business Concerns (SBCs), which may be accomplished in a number of ways, including the use of multiple program directors/principal investigators. 

Examples of neurotechnologies that would be appropriate for this FOA include, but are not limited to, development of: 

While some of the markets for these products may be small, NIH is supportive of developing these technologies towards sustainable commercial manufacture. The full development and dissemination of these technologies will enable neuroscientists to perform novel hypothesis-driven experiments that are not feasible and/or reduce barriers to experiments that currently are too costly, difficult, or time consuming to perform broadly.   

For more information about neurotechnologies that may be of interest for this FOA, please see the BRAIN website:  https://www.braininitiative.nih.gov/index.htm

Projects with non-exempt human subjects research will not be supported by this FOA. Such projects will not be accepted to this FOA.

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

    • Probes for large scale sensing and/or manipulation of neural activity in vivo
    • Imaging instrumentation for recording and/or manipulating neural activity in vivo
    • Electrodes for large-scale recording and/or circuit manipulation in vivo
    • Techniques and approaches for recording/manipulating neural activity during behaviors
    • Novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function  
    • Software or hardware related to the BRAIN initiative

Better Defining Growth Medium to Improve Reproducibility of Cell Culture (SBIR) (R43/R44 - Clinical Trial Not Allowed)

  1. Fetal bovine serum (FBS) is the most widely used growth supplement for cell culture; it cost-effectively supports the survival, growth, and differentiation of many cell lines by providing nutrients, growth signals, and protection from stress. Although serum is an effective growth promoter, it is variable in its composition, activity, and effects on cellular phenotypes. This variability introduces inconsistencies into research using cultured cells. Sometimes it is possible to replicate experimental results only if the same manufacturer's serum is used; sometimes replication is only possible using serum from the same lot. Vendor literature and scientific reviews advise investigators to test lots of serum to identify those that support the desired cellular responses, and then buy a quantity of the best lot for long term use. This practice is widespread but can make replication of results by others difficult.

    Serum contains hundreds, perhaps thousands, of constituents. These include macromolecules, small molecules, and trace elements; for any cell line a large and variable subset of these may be active in supporting cell growth. The composition and concentrations of factors in serum vary with the source animals' diets, geographical locations, gestational stages, gender, health, season of harvesting, and histories of exposures to hormones, antibiotics, and environmental chemicals. Harvesting practices, manufacturing processes and additives, and differences in quality control and handling introduce additional variation. Serum is a byproduct of the meat-processing industry; dependence on serum is a barrier to translation of cell-based therapies because of the risk of transmission of viruses, prions, endotoxins, and immunogens.

    Serum supplies factors that support cell growth through mechanisms that are not well understood, but includes hormones, enzymes, extracellular vesicles and proteins, extracellular matrix constituents, attachment and spreading factors, vitamins and minerals, trace elements, lipids, protease inhibitors, and other stabilizing and detoxifying factors. Substitute formulations for serum are expensive and time-consuming to develop and are cell-type specific; some cell lines cannot be grown with presently-available serum replacements. Although serum substitutes can support the growth of many cell types in culture, they often do not support robust survival and the same range of responses as does serum. Thus, serum continues to be widely used in many research settings where it is not economically practical to customize substitutes for it.

    This Funding Opportunity Announcement (FOA) addresses the needs of developers and users for supporting technologies and products to expedite (a) development of better serum substitutes, (b) identification of serum constituents that are effective in promoting the culture and responses of specific cell lines, and (c) troubleshooting of experimental variation stemming from variability in serum. This FOA will support SBIR projects to develop reliable and cost-effective tools; projects may develop new technologies or improve upon existing technologies. Topics include, but are not limited to:

    • Synthetic serum replacements, both general purpose and specialized for particular cell types. Development of minimal base formulations for customization by users into serum substitutes for specific cell lines.
    • General purpose analytical tools to detect constituents in serum. Tools for rapid evaluation of variation in serum composition, and for comparison of serum batches.
    • Specialized methods, tools and products for identification and evaluation of factors and activities in serum affecting adherence, survival and phenotypes of particular cell types.
    • Development of bioactive products for inclusion in serum replacements or to supplement reduced media, such as components that would assist the adherence of cells and promote correct morphology.
    • Affordable methods for production of serum components such as growth factors.
    • Toolkits to assist users to develop serum replacements.
    • Methods, tools, and products for detecting and clearing biological and chemical contaminants, such as viruses, prions, endotoxins, immunogens, etc.

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

Wearable Alcohol Biosensors (SBIR) (R43/R44- Clinical Trial Optional)

  1. Rapid advances are being made in wearable technology, including clothing, jewelry and other devices with broadly diverse functions that meet medical or consumer needs.  This FOA seeks applications from small businesses that propose to design and produce a non-invasive wearable device to monitor blood alcohol levels in real time.

    Alcohol detection technology for personal alcohol monitoring has been successful in judicial and law enforcement settings, yet needs significant modification for wider use in other situations.  Current technological developments in electronics, miniaturization, wireless communication, and biophysical techniques of alcohol detection in humans increase the likelihood of successful development of a general use alcohol biosensor in the near future.

    The alcohol biosensor device should be unobtrusive, appealing to the wearer, and can take the form of jewelry, clothing, or any other format located in contact with the human body. Techniques to quantitate alcohol in blood or interstitial fluid are highly encouraged. Highest priority will be given to technologies that depart from measuring alcohol in sweat or sweat vapor.  Applicants are encouraged to pursue any technology - including but not limited to biophysical, optical, wave, or other novel approaches- that works in a non-invasive way and can be incorporated into a wearable.

    The device should be able to quantitate blood alcohol level, interpret, and store the data or transmit it to a smartphone or other device by wireless transmission.  The device should have the ability to verify standardization at regular intervals and to indicate loss of functionality.  The power source should be dependable and rechargeable.  Data storage and transmission must be completely secure in order to protect the privacy of the individual.  A form of subject identification would be an added benefit.  The device can be removable. 

    It is envisioned that wearable alcohol monitors will serve useful purposes in research, clinical, and treatment settings, will play a role in public safety, and will be of interest to individuals interested in keeping track of personal health parameters. Designs may emphasize any of these potential market subsets or may seek to be broadly marketable.     

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

Páginas