BRAIN Initiative: Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (U44 Clinical Trial Required)

BRAIN Initiative: Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (U44 Clinical Trial Required) is sponsored by National Institutes of Health (NIH) - BRAIN Initiative. This funding opportunity encourages small business concerns to pursue translational non-clinical and clinical studies for recording and/or stimulating devices to treat nervous system disorders, directly relevant to neurosurgical brain technologies.

Expired RFA-NS-16-011: BRAIN Initiative: Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (U44) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Institute of Neurological Disorders and Stroke ( NINDS ) National Institute on Aging ( NIA ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) Eunice Kennedy Shriver National Institute of Child Health and Human National Institute on Drug Abuse ( NIDA ) National Center for Complementary and Integrative Health ( NCCIH ) National Eye Institute ( NEI ) National Institute on Deafness and Other Communication Funding Opportunity Title BRAIN Initiative: Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous U44 Small Business Innovation Research (SBIR) Cooperative September 29, 2016 - This RFA has been reissued as RFA-NS-17-007 .

January 29, 2016 - Notice of NIH/FDA Informational Webinar - Common Misunderstandings of the Investigational Device Exemption Process for Invasive Neuromodulation Devices. See Notice NOT-NS-16-006 .

- NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015) Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity UH2/UH3 Cooperative Agreement UH3 Cooperative Agreement RFA-NS-16-018 U44 Cooperative Agreement (Direct to Phase II) Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 853; 93.

865; 93. 866; 93. 286; 93.

273; 93. 279; 93. 213; Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to encourage small business concerns (SBCs) to pursue translational non-clinical studies and clinical studies for recording and/or stimulating devices to treat nervous system disorders and thereby better understand the human brain.

The program will utilize a cooperative agreement mechanism to support the non-clinical studies necessary for the submission of an Investigational Device Exemption (IDE) for a Significant Risk (SR) study or to obtain Institutional Review Board (IRB) approval for a Non-Significant Risk (NSR) study, and the subsequent small clinical study (e.g., Early Feasibility Study).

Activities supported in this program include implementation of clinical prototype devices, non-clinical safety and efficacy testing, design verification and validation activities, and pursuit of regulatory approval for, and implementation of, a single small clinical study. The small clinical study should provide data to answer key questions about the function or final design of a device.

This final device design may require most, if not all, of the non-clinical testing on the path to more advanced clinical trials and market approval. The clinical study is expected to provide information that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) April 26, 2016, by 5:00 PM local time of applicant Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s) Required Application Instructions It is critical that applicants follow the instructions in (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 1. Overview Information Part 2. Full Text of the Announcement I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I. Funding Opportunity Description through A dvancing I nnovative N eurotechnologies ( 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 treat, cure, and even prevent 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 2016 are based on careful consideration by the NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group ( http://braininitiative.

nih. gov/mcwg. htm ).

In addition to its contributions to the Federal BRAIN Initiative, NIH continues to have a substantial annual investment in neuroscience research. The Institutes and Centers contributing to the NIH BRAIN Initiative (listed at http://braininitiative. nih.

gov/ ) provide separate support for neuroscience research through applications received via parent announcements as well as through specific FOAs. Potential applicants to this FOA are strongly encouraged to contact Scientific/Research staff if they have any questions about the best funding opportunity announcement for their research.

This Funding Opportunity Announcement (FOA) is related to Section III of the BRAIN 2025 Report, and addresses the goal of developing "innovative technologies to understand the human brain and treat its disorders". Initial first-in-human studies are a key point in the development of innovative new clinical technologies.

The leap from animal studies to humans is large, and initial clinical studies are often necessary to address critical scientific questions about the function of a device in human patients and/or inform a final device design suitable for eventual FDA market approval.

Initial demonstrations of novel device function in humans have become increasingly required to encourage the industry and venture capital investment necessary to develop a final safe, reliable, and efficacious device that can be manufactured at scale suitable for regulatory approval, yet at a price point sufficient for sustainable commercial market given insurance As recommended in the BRAIN 2025 Report, this FOA will support non-clinical testing necessary to enable initial clinical studies of "implantable devices with recording and/or stimulation capabilities that both advance clinical diagnostic or therapeutic applications and maximize their scientific research value", and a subsequent small clinical study for such devices.

Clinical studies supported may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board (IRB), or Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the FDA, such as chronic The purpose of this FOA is to encourage small business concerns (SBCs) to pursue translational and clinical studies for recording and/or stimulating devices to treat nervous system disorders and better understand the human brain.

This FOA utilizes a cooperative agreement mechanism to support non-clinical testing to enable IRB approval and/or a successful IDE submission necessary to conduct a small clinical study, and the subsequent small clinical study (e.g., Early Feasibility Study, see http://www. fda. gov/downloads/MedicalDevices/DeviceRegulati%20onandGuidance/GuidanceDocuments/UCM279103.

pdf2 for details/definition). This funding opportunity supports non-clinical testing and clinical studies to answer key questions about the function or final design of a device. This final device design may require most, if not all, of the non-clinical testing on the path to more advanced clinical trials and market approval.

The clinical study is expected to provide information that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use, yet is critical to enable next-generation diagnostic or therapeutic devices.

Activities that can be supported in this program include testing of clinical prototype devices, design verification and validation activities, demonstration of non-clinical safety and efficacy, pursuit of U.S. regulatory approval for clinical study, and a single small clinical study.

As applicants must have comprehensive supporting data, including proof-of-concept demonstration with a near final prototype in a relevant animal model prior to entry, innovation will in part be judged on presenting a credible path towards an IDE or an NSR clinical study. All projects will have two phases, Phase I and Phase II, using the Fast-track mechanism.

The initial Phase I will support non-clinical testing toward filing of an IDE for an SR study or obtaining IRB approval for an NSR clinical study. All projects will start at Phase I, and the length of Phase I will depend on the maturity of the project at entry. Only those Phase I projects that have met specific criteria (see below) will transition to the subsequent Phase II after NIH administrative review.

The Phase II will support This FOA is milestone-driven and involves NIH program staff's participation in developing the project plan, monitoring the research progress, and making go/no-go decisions. NIH staff will also provide assistance to academic investigators in familiarizing them with the clinical device development process and the criteria needed to advance therapeutic leads and diagnostics to the clinic.

The expectations of the program are in line with those of industry in regards to advancing devices through the translational developmental pipeline. As such, an inherent high rate of attrition is expected within this program. For this funding opportunity announcement phase I clinical testing, studies or trials refer to the common phases of a clinical trial.

U44 Phase I and II refer to the project phases of the SBIR program.

For entry to the program, projects should have: Comprehensive Supporting Data: Proof-of-concept data of device function are required using a prototype device equivalent to the final device design anticipated for clinical testing, ideally obtained using an in vivo model representative of the intended patient population A compelling case for a successful IDE submission to support the clinical component, or IRB approval for an NSR study, within the period of the Overall device development plan, including timeline for contact and interaction with appropriate regulatory bodies, clinical considerations, Identification of one or more clinically meaningful device outcome measures based on input from both clinicians and patients Examples of studies that can be proposed during the non-clinical Phase I include, but are not limited to: Non-GLP (Good Laboratory Practice) animal studies to develop surgical techniques relevant to the device, define relevant therapeutic parameters, In vitro and animal testing to meet FDA recognized ISO/ASTM Standards Activities to become GMP (Good Manufacturing Practice) compliant Activities to bring the development process under Design and Device, software, and firmware design verification and validation GLP compliant large animal model safety and/or testing of an Activities to support submission of an IDE Phase II will support a small clinical study to answer key questions about the function or final design of a device.

Examples of studies that can be proposed during the clinical phase include, but are not limited to: Optimization of the device design with respect to the human Identification of the most simple, reliable, and cost effective device configuration for more advanced clinical trials and eventual market Basic proof-of-concept testing in human patients Studies of the key physiological variables that may impact the function of the device in humans Initial assessments of device safety are expected, but only in conjunction with obtaining enabling data about device design or function Following Activities are Non-Responsive to this FOA, and Will Not Be Reviewed: Basic research and studies of disease mechanisms Animal model development: All in vivo models must have been previously established and characterized Rehabilitation strategies Definitive clinical trials of therapeutic devices, such as a traditional Feasibility study and/or Pivotal Trial (see http://www.

fda. gov/downloads/MedicalDevices/DeviceRegulati%20onandGuidance/GuidanceDocuments/UCM279103.

pdf2 for the definition of an Early Feasibility Study, Feasibility Study and Pivotal Efforts to develop neurotechnology for fundamental study of the Fundamental basic/applied research projects that employ existing market-approved devices for their labeled uses are outside the scope of this FOA but may be within scope of future BRAIN FOAs Projects focused on augmentation of neural function in healthy Technologies exclusively intended for implant outside of the CNS that do not treat CNS disorders or provide knowledge about CNS function.

This includes dorsal root ganglion, peripheral, or cranial nerve modulation for the treatment of peripheral nervous system disorders. As a cooperative agreement, implementation will involve the participation of NIH program staff in the planning and execution of the are strongly encouraged to consult with NIH Scientific/Research staff when planning an application.

Early contact provides an opportunity for NIH scientific/research staff to provide guidance on program scope, goals, and appropriate yearly milestones with metric driven criteria that can be verified by NIH staff for sufficiency. Applicants should contact NIH Scientific/Research staff as early as possible before the receipt date. Information for award authorities and regulations.

Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for this FOA. Application Types Allowed Glossary and the SF424 (R&R) SBIR/STTR Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards NIH intends to commit up to $6,500,000 in FY2016 to fund approximately five awards. Application budgets are not limited but must reflect the actual needs of the proposed project.

Applications should rarely exceed $1,000,000 in total cost per year during the Phase I and $1,500,000 in total costs per year during the Durations up to 2 years for Phase I and up to 3 years for Phase II may be requested. Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA. 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: 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, 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; 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), or any combination of 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; OR 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. 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.

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 Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity 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. 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.

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. 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 receive a new Phase I award. This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5 year period.

Companies that apply for a Phase I award and do not meet or exceed the benchmark rate will not be eligible for a Phase I 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 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.

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 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 receive New Phase I, Fast-track or Direct Phase II awards for a period of one year. Non-domestic (non-U.S.) Entities (Foreign Institutions) are 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 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 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 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 System for Award Management (SAM) (formerly CCR) 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. 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.

must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration.

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 must have an active DUNS number and SAM registration in order to complete the 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.

Eligible Individuals (Program Director/Principal Investigator) 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. This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility 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 The NIH will not accept duplicate or highly overlapping applications under review at the same time.

This means that the NIH will A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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.

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

In Phase II, normally, a minimum of one-half or 50% of the research or analytical effort must be 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 generally may not exceed 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

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 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. and Submission Information Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants. gov .

2. Content and Form of Application Submission It is critical that applicants follow the instructions in (R&R) SBIR/STTR Application Guide , including Supplemental Grant Application Instructions 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 For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant All page limitations described in the SF424 (R&R) SBIR/STTR Application Guide and the Table of Page Limits must be followed.

for Application Submission The following section supplements the instructions found in the SF 424 (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. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

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

Attachments: Applicants are required to include the following Clinical Protocol Synopsis Long-Term Plan for Patients These items must be uploaded as separate attachments in pdf format with filenames that correspond to the individual items (SBA Company Registry, Needs Assessment, Team Management Plan, Clinical Protocol Synopsis, and