NCI SBIR FY23 Concept Award Solicitation.pdf

NATIONAL CANCER INSTITUTE (NCI)

SMALL BUSINESS INNOVATION RESEARCH (SBIR)

INNOVATIVE CONCEPT AWARD PROGRAM

PROGRAM SOLICITATION 75N91022R00006

Closing Date: August 22, 2022

IMPORTANT

Deadline for Receipt of Proposals: Proposals must be received before 5:00 PM Eastern Daylight Time, August 22, 2022.

IMPORTANT: All proposals must be submitted using the electronic contract proposal submission

(eCPS) website, as discussed in Section 7 of this solicitation.

Deadline for Receipt of White Papers: White Papers must be received before 5:00 PM Eastern Daylight Time, May 2, 2022.

White Papers must be submitted via e-mail to ncioasbir@mail.nih.gov, as discussed in Section 7 of this solicitation.

All questions shall be submitted via e-mail to ncioasbir@mail.nih.gov. As discussed in Section 7 of this solicitation, to ensure that your question is answered, it should be submitted by May 2, 2022.

After that time, questions will be addressed as time permits, at the discretion of the NCI Office of Acquisitions.

Questions may be shared with the public via a solicitation amendment to ensure fair competition. Do not include sensitive information in questions submitted.

Please read the entire solicitation carefully prior to submitting your proposal.

Please go to https://www.sbir.gov/sites/default/files/SBIR-STTR_Policy_Directive_2019.pdf to read the

SBIR/STTR Policy Directive issued by the Small Business Administration for further information.

For information about this solicitation, the primary point of contact is listed below:

Cherie Wells, SBIR Contracts Analyst (Contractor)

Office of Acquisitions, National Cancer Institute ncioasbir@mail.nih.gov

(240) 276-7255

Issued by: Michael Heaney, Office of Acquisitions, National Cancer Institute.

mailto:ncioasbir@mail.nih.gov mailto:ncioasbir@mail.nih.gov https://www.sbir.gov/sites/default/files/SBIR-STTR_Policy_Directive_2019.pdf mailto:ncioasbir@mail.nih.gov

Page ii

Table of Contents

1 INTRODUCTION

2 PROGRAM DESCRIPTION

2.1 Objectives

2.2 Three Phase Program

2.3 I-Corps™ at NIH

3 DEFINITIONS

3.1 General Definitions

3.2 Definitions (Relating to R&D)

4 PROPOSAL FUNDAMENTALS

4.1 Introduction

4.2 Offeror Eligibility and Performance Requirements

4.3 SBIR/STTR Performance Benchmarks for Progress towards Commercialization

4.4 Multiple Principal Investigators

4.5 Joint Ventures and Limited Partnerships

4.6 Majority Ownership in Part by Multiple Venture Capital, Hedge Fund, and Private Equity Firms

4.7 Conflicts of Interest

4.8 Market Research

4.9 Debriefing

4.10 Registrations and Certifications

4.11 Promotional Materials, URLs, and Other Media

4.12 Prior, Current, or Pending Support of Similar Proposals or Awards

4.13 Reporting Matters Involving Fraud, Waste, and Abuse

4.14 Technical and Business Assistance / State Assistance

4.15 Payment

4.16 Proprietary Information

4.17 Identification and Marking of SBIR Technical Data in Contract Reports and Deliverables

5 CONTRACT REQUIREMENTS

5.1 NIH Policy on Enhancing Reproducibility Through Rigor and Transparency

5.2 CARE OF LIVE VERTEBRATE ANIMALS, HHSAR 352.270-5(b) (December 2015)

5.3 Animal Welfare

5.4 PROTECTION OF HUMAN SUBJECTS, HHSAR 352.270-4(b) (December 2015)

5.5 Required Education in the Protection of Human Research Participants

5.6 Copyrights

5.7 Technical Data Rights

5.8 Patents and Invention Reporting

5.9 Other Contract Requirements

6 METHOD OF EVALUATION

6.1 Evaluation Process

6.2 Award Decisions

6.3 Technical Evaluation Criteria

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7 PROPOSAL SUBMISSION

7.1 White Paper / Letter of Intent

7.2 Questions

7.3 Limitation on the Length of the Technical Proposal

7.4 Submission, Modifications, Revision, and Withdrawal of Proposals

8 PROPOSAL PREPARATION AND INSTRUCTIONS

8.1 Introduction

8.2 Proposal Instructions

8.3 Technical Proposal Cover Sheet

8.4 Abstract of Research Plan and Public Health Relevance

8.5 Technical Proposal Content Generated by Small Business Offeror

8.6 Enhancing Reproducibility through Rigor and Transparency

8.7 Research Involving Vertebrate Animals

8.8 Human Subjects and Clinical Trials Information Form

1) Human Specimens and/or Data

2) Human Subjects Research with an Exemption from Federal Regulations

3) Protection of Human Subjects

8.9 Content of the Pricing Proposal

9 ANTICIPATED SCHEDULED AND NUMBER OF AWARDS

10 SCIENTIFIC AND TECHNICAL INFORMATION SOURCES

11 TECHNICAL TOPIC DESCRIPTION(S)

National Cancer Institute (NCI)

12 ATTACHMENT(S) AND APPENDICES

1 INTRODUCTION

The National Cancer Institute invites small business concerns to submit research proposals under this Small

Business Innovation Research (SBIR) Contract Solicitation. Firms with the capability to conduct research and development (R&D) in the health-related topic areas referred to below and described more fully in Section 11.0, and to commercialize the results of that R&D, are encouraged to participate.

The topic areas that are being sought under this solicitation are:

The National Cancer Institute is soliciting proposals from small business concerns who are looking for an opportunity to perform a few key activities to demonstrate proof-of-concept and feasibility of untested but potentially transformative, game-changing research and development (R&D) technologies to help cancer patients, providers and care-givers, in conjunction with Small Business Innovation Research (SBIR) program objectives.

The NCI has established a high-risk, high-reward SBIR “Innovative Concept Award” Program for this purpose.

Preliminary data is not required; however, the ideas should have sound scientific premise either based on the offeror’s own research or literature evidence. Proposals will need to identify an anticipated product that will be developed and clearly lay out the anticipated development path. Proposals will need to clearly identify the clinical problem and cancer type(s) that the proposal will focus on with adequate justification. In addition, the offerors should propose experiments to obtain initial de-risking and proof-of-concept data.

Note: Non-exempt Human subjects research will not be supported under this solicitation.

All firms submitting a proposal for an SBIR Concept Award must also include potential participation in the

I-Corps™ at NIH program in its proposal. See more information about I-Corps™ at NIH in Section 2.3 of this solicitation.

There will be no opportunity to move directly on from this concept award into a subsequent SBIR contract. Firms that receive a concept award originating from this solicitation will be able to apply for continuing support under other existing SBIR funding opportunities, such as a Phase I grant, a Fast Track award, or a Phase II grant predicated on this concept award contract.

The HHS is not obligated to make any awards under this solicitation. All awards are subject to the availability of funds. HHS is not responsible for any monies expended by the offeror before award of any contract.

• Development of therapeutic technologies for treatment or prevention of

Pediatric Cancers and/or Rare Cancers.

For this solicitation rare cancers with a 5-year survival rate of less than 50 % are encouraged.

• Development of devices or diagnostic technologies for treatment, detection, and diagnosis of Pediatric Cancers and/or Rare Cancers.

For this solicitation, rare cancers with a 5-year survival rate of less than 50 % are encouraged.

2 PROGRAM DESCRIPTION

2.1 Objectives

The objectives of the SBIR program include stimulating technological innovation in the private sector, strengthening the role of small business in meeting Federal research or research and development (R/R&D) needs, increasing private sector commercialization of innovations developed through Federal SBIR R&D, increasing small business participation in Federal R&D, and fostering and encouraging participation by socially and economically disadvantaged small business concerns and women-owned small business concerns in the SBIR program.

The basic design of the NCI SBIR program is in accordance with the Small Business Administration (SBA) SBIR

Program Policy Directive dated May 2, 2019. This SBIR contract solicitation strives to encourage scientific and technical innovation in areas specifically identified by the NCI. The guidelines presented in this solicitation reflect the flexibility provided in the Policy Directive to encourage proposals based on scientific and technical approaches most likely to yield results important to the NCI and to the private sector.

2.2 Three Phase Program

The Federal-wide SBIR program consists of three separate phases.

Phase I: Feasibility

The objective of Phase I is to determine the scientific or technical feasibility and commercial merit of the proposed research or R&D efforts and the quality of performance of the small business concern, prior to providing further Federal support in Phase II.

Phase II: Full R/R&D Effort

The objective of Phase II is to continue the research or R&D efforts initiated in Phase I. Funding shall be based on the results of Phase I and the scientific and technical merit and commercial potential of the Phase II proposal.

Phase III: Commercialization stage without SBIR funds

The objective of Phase III is for the small business concern to pursue, with non-SBIR funds, the commercialization objectives resulting from the outcomes of the research or R&D funded in Phases I and II.

Phase III may be funded by non-Federal sources of capital or may be funded by follow-on non-SBIR Federal funding agreements.

Additionally, the NCI offers a Phase IIb program:

NCI Phase IIB Bridge Award

The National Cancer Institute would like to provide notice of a recent funding opportunity entitled the SBIR

Phase IIB Bridge Award. This notice is for informational purposes only and is not a call for Phase IIB Bridge

Award proposals. This informational notice does not commit the government to making such awards to contract awardees.

Successful transition of SBIR research and technology development into the commercial marketplace is difficult, and SBIR Phase II awardees often encounter significant challenges in navigating the regulatory approval process, raising capital, licensure and production, as they try to advance their projects towards commercialization.

The NCI views the SBIR program as a long-term effort; to help address these difficult issues, the NCI has developed the SBIR Phase IIB Bridge Award under the grants mechanism. The previously offered Phase IIB

Bridge Award was designed to provide additional funding of up to $4M for a period of up to three additional years to facilitate the transition of SBIR Phase II projects to the commercialization stage. The specific requirements for the previously offered Phase IIB Bridge Award can be reviewed in the full RFA announcement:

https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-19-047.html.

In FY2011, the NCI expanded the Phase IIB Bridge Award program to allow previous SBIR Phase II contract awardees to compete for SBIR Phase IIB Bridge Award grants. Provided it is available in the future, the Phase IIB

Bridge Award program will be open to contractors that are successfully awarded a Phase II contract (or have an exercised Phase II option under a Fast-Track contract). NIH SBIR Phase II contractors who satisfy the above requirements may be able to apply for a Phase IIB Bridge Award under a future Phase IIB Bridge Award grant funding opportunity announcement (FOA), if they meet the eligibility requirements detailed therein. Selection decisions for a Phase IIB Bridge Award will be based both on scientific/technical merit as well as business/commercialization potential.

2.3 I-Corps™ at NIH

Any offeror submitting a proposal must include potential participation in the I-Corps™ at NIH program.

The I-Corps™ at NIH program is designed to complement activities within the scope of an initial SBIR award.

This opportunity is specifically aligned with the statutorily mandated purpose of the SBIR program to “increase private sector commercialization of innovations derived from Federal R/R&D, thereby increasing competition, productivity and economic growth.” 48 CFR 1819.7301.

The I-Corps™ at NIH program is selective, with each NIH cohort consisting of up to 24 companies, split amongst current grant and contract SBIR award recipients throughout the NIH. For a firm fixed price option amount not to exceed $55,000 (in addition to the price for performing the base research project), companies selected to participate in this program will perform additional requirements and develop additional deliverables which will ultimately provide the resources to submit a refined Commercialization Plan within the Final Report for an SBIR award, meaning that I-Corps™ at NIH participation runs concurrently with the performance of the SBIR research.

Participants must assemble a three-member I-Corps™ team that will work collaboratively to complete the program’s required activities and assignments. Applicants should designate teams consisting of the following 3 members/roles:

• Chief-Level Corporate Officer

(CEO of the SBIR awardee company strongly preferred)

• Industry Expert

(internal, such as a Business Development Manager or Board Member, or external, such as a consultant or mentor with the National Innovation Network)

• Program Director/Principal Investigator (PD/PI)

(or, in the case that PD/PI is also the CEO, an additional technical/scientific expert)

To successfully complete the I-Corps™ at NIH Program, the entire I-Corps™ team must be deeply committed and dedicated to the time-intensive curriculum. Each team member should plan to spend at least 20 hours per week on I-Corps™ activities for the full duration of the 8-week program. Attendance of all 3 team members is mandatory for a 3-day immersion ‘kickoff’ workshop and a 2-day closing workshop, where team members will give presentations as well as participate in lectures and training sessions. There will also be weekly webinar sessions and requirements to get “out of the lab” and gather information by conducting at least 100 discovery interviews with potential customers, strategic partners, and other third-party stakeholders.

https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-19-047.html https://venturewell.org/i-corps/nih/

The program teaches researchers how to gain a clearer understanding of the value of their inventions in the marketplace, and ultimately how to advance their technologies from the research lab into the commercial world, helping to accelerate the commercialization of new products and services derived from NIH SBIR awards.

See https://sbir.cancer.gov/programseducation/icorps for further information on this program. Example timelines for the selection process and for course components may be viewed here, although specific dates are subject to change: https://sbir.cancer.gov/programseducation/icorps/cohortcurriculum.

Application Process

The first step in the I-Corps™ at NIH application process is submitting an additional, separate “Appendix C –

Contract Pricing Proposal,” in your Business Proposal. Specify “I-Corps” in the “Title of Proposal” field. This separate budget must not exceed $55,000 in total direct costs – indirect costs may not be included. Of that amount, $22,000 must go towards covering workshop registration fees, which should be listed in field 4.e.

OTHER of Appendix C. Remaining budget should be allocated as appropriate to cover personnel time for the I-

Corps™ team members – at least 20 hours per week for 8 weeks for the 3 team member roles discussed above – as well as travel costs as necessary to conduct on-site customer development interviews within the U.S.

Dates and times for NIH 8-week cohorts in 2022-2023 have not yet been finalized. The Government will notify awardees once these determinations have been made.

Contracts resulting from this solicitation will have a contractual option for I-Corps™ participation;

however, this is not a guarantee of funding unless and until the Government exercises the option at a later date. The Government may exercise the option in the event that the company is ultimately selected for participation in an I-Corps™ at NIH cohort and funds are available.

The second step in the I-Corps™ application process will take place during performance of the SBIR research project, when the Government will notify awardees of the definitized details for the planned cohorts and ask awardees to prepare a brief application to be considered for I-Corps™ selection among various SBIR awardees from around the NIH and CDC, subject to availability of funds. The application will consist of components such as those discussed below (not required at the time of submission of this proposal):

• Executive Summary of Predicate SBIR/STTR Contract and Team (1 page only)

• I-Corps™ Team and Project Plan (up to 5 pages) o I-Corps™ Team

Description of the I-Corps™ team; indication of commitment to meet time-intensive requirements;

discussion of team’s willingness to modify/refine the overall commercialization strategy based on knowledge gained during the course of the I-Corps™ Program.

o Potential Commercial Impact

Description of what has led team to believe that a commercial opportunity exists for the project;

profile of typical customer; description of the customer’s need that the proposed innovation will meet and how the customer is currently meeting that need; discussion of competitive advantage offered by the proposed product/service; discussion of how much a customer would pay for the solution.

o Project Plan

Description of the current stage of development for the product/service and what objectives will be achieved by the end of the Phase I project; description of next steps the company will take to advance the project toward commercialization.

https://sbir.cancer.gov/programseducation/icorps https://sbir.cancer.gov/programseducation/icorps/cohortcurriculum

Finally, after NIH reviews written I-Corps™ applications, it will conduct phone interviews to determine which companies will be invited to join the planned I-Corps™ cohort(s). The NIH selection committee will consider the ability of the proposed I-Corps™ effort to increase the overall success of the SBIR research project. (Specific criteria will be discussed in the notification provided by the Government containing finalized application due dates and cohort participation dates.)

If a company is selected, the I-Corps™ option in the contract may be exercised (pending availability of funds), increasing funding to the contract and incorporating I-Corps™ program participation requirements and associated deliverables into the contract, including:

• Participation in all Opening Workshop lectures/sessions;

• 3 team presentations at the Opening Workshop;

• Participation in weekly faculty office hour meetings;

• Participation in 6 Webex sessions;

• Completion of at least 100 customer discovery interviews;

• Participation in all Closing Workshop lectures/sessions

• Final Lessons Learned team presentation; and,

• Team presentation of final video.

Information obtained through the above I-Corps™-related efforts must be incorporated into a Commercialization

Plan component of the Final Report.

3 DEFINITIONS

3.1 General Definitions

The following definitions from the SBA Policy Directive and the Federal Acquisition Regulation (FAR) apply for the purposes of this solicitation:

8(a) firm. A small business concern that is participating in the Small Business Administration’s 8(a) Business Development

Program for firms that are owned and controlled at least 51% by socially and economically disadvantaged individuals.

Applicant. The organizational entity that qualifies as an SBC at all pertinent times and that submits a contract proposal or a grant application for a funding agreement under the SBIR Program.

Affiliate. This term has the same meaning as set forth in 13 CFR part 121—Small Business Size Regulations, section

121.103. How does SBA determine affiliation? (Available at http://www.ecfr.gov/cgi-bin/text-idx?SID=b02d16dbfcddf646e5c0728d5e632a61&mc=true&node=se13.1.121_1103&rgn=div8). Further information about

SBA's affiliation rules and a guide on affiliation is available at www.SBIR.gov and www.SBA.gov/size.

Animal. Any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes.

Awardee. The organizational entity receiving an SBIR award.

Commercialization. The process of developing products, processes, technologies, or services and the production and delivery (whether by the originating party or others) of the products, processes, technologies, or services for sale to or use by the Federal government or commercial markets.

Consultant. An individual who provides professional advice or services for a fee, but normally not as an employee of the engaging party. In unusual situations, an individual may be both a consultant and an employee of the same party, receiving compensation for some services as a consultant and for other work as a salaried employee. To prevent apparent or actual conflicts of interest, awardees and consultants must establish written guidelines indicating the conditions of payment of consulting fees. Consultants may also include firms that provide paid professional advice or services.

Contract. An award instrument establishing a binding legal procurement relationship between a funding agency and the recipient, obligating the latter to furnish an end product or service and binding the agency to provide payment therefore.

Covered Small Business Concern. A small business concern that:

(1) Was not majority-owned by multiple venture capital operating companies (VCOCs), hedge funds, or private equity firms on the date on which it submitted an application in response to a solicitation under the SBIR program; and

(2) Is majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms on the date of the SBIR award.

eCPS. The Electronic Contract Submission (eCPS) website is a component of the Government’s integrated, secure system for the electronic submission, capture, tracking, and review of contract proposals. The eCPS website will be the only way to submit proposals under this solicitation. See the Section on Proposal Submissions for further information.

Essentially Equivalent Work. Work that is substantially the same research, which is proposed for funding in more than one contract proposal or grant application submitted to the same Federal agency or submitted to two or more different Federal agencies for review and funding consideration; or work where a specific research objective and the research design for accomplishing the objective are the same or closely related to another proposal or award, regardless of the funding source.

Feasibility. The practical extent to which a project can be performed successfully.

http://www.ecfr.gov/cgi-bin/text-idx?SID=b02d16dbfcddf646e5c0728d5e632a61&mc=true&node=se13.1.121_1103&rgn=div8 http://www.ecfr.gov/cgi-bin/text-idx?SID=b02d16dbfcddf646e5c0728d5e632a61&mc=true&node=se13.1.121_1103&rgn=div8 https://www.sbir.gov/ http://www.sba.gov/size

Federal Agency. An executive agency as defined in 5 U.S.C. § 105, and a military department as defined in 5 U.S.C. 102

(Department of the Army, Department of the Navy, Department of the Air Force), except that it does not include any agency within the Intelligence Community as defined in Executive Order 12333, section 3.4(f), or its successor orders.

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.

Fraud, Waste, and Abuse.

Fraud includes any false representation about a material fact or any intentional deception designed to deprive the United

States unlawfully of something of value or to secure from the United States a benefit, privilege, allowance, or consideration to which an individual or business is not entitled.

Waste includes extravagant, careless or needless expenditure of Government funds, or the consumption of Government property, that results from deficient practices, systems, controls, or decisions.

Abuse includes any intentional or improper use of Government resources, such as misuse of rank, position, or authority or resources.

Funding Agreement. Any contract, grant, or cooperative agreement entered into between any Federal agency and any SBC for the performance of experimental, developmental, or research work, including products or services, funded in whole or in part by the Federal Government.

Funding Agreement Officer. A contracting officer, a grants officer, or a cooperative agreement officer.

Grant. A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. A grant is used whenever the Federal agency anticipates no substantial programmatic involvement with the awardee during performance.

HUBZone Small Business Concern. A small business concern that appears on the List of Qualified HUBZone (Historically

Underutilized Business Zone) Small Business Concerns maintained by the Small Business Administration (13 CFR 126.103).

Innovation. Something new or improved, having marketable potential, including: (1) development of new technologies, (2) refinement of existing technologies, or (3) development of new applications for existing technologies. Innovation encompasses the full commercialization pathway.

Intellectual Property. The separate and distinct types of intangible property that are referred to collectively as “intellectual property,” including but not limited to: (1) Patents; (2) trademarks; (3) copyrights; (4) trade secrets; (5) SBIR technical data

(as defined in this section); (6) ideas; (7) designs; (8) know-how; (9) business; (10) technical and research methods; (11) other types of intangible business assets; and (12) all types of intangible assets, either proposed or generated by an SBC as a result of its participation in the SBIR Program.

Joint Venture. A joint venture is an association of individuals and/or concerns with interests in any degree or proportion consorting to engage in and carry out no more than three specific or limited-purpose business ventures for joint profit over a two year period, for which purpose they combine their efforts, property, money, skill, or knowledge, but not on a continuing or permanent basis for conducting business generally. See 13 CFR 121.103(h) for further information.

Key Personnel. The principal investigator/project manager and any other person considered to be essential to work performance.

Principal Investigator/Project Manager. The one individual designated by the applicant to provide the scientific and technical direction to a project supported by the funding agreement.

Program Solicitation. A formal solicitation for proposals issued by a Federal agency that notifies the small business community of its R/R&D needs and interests in broad and selected areas, as appropriate to the agency, and requests proposals from SBCs in response to these needs and interests.

http://www.gpo.gov/fdsys/granule/USCODE-2011-title5/USCODE-2011-title5-partI-chap1-sec102/content-detail.html http://www.ecfr.gov/cgi-bin/text-idx?SID=fc49fc7e1268cd0891cc2dde9abe523f&mc=true&node=se13.1.121_1103&rgn=div8

Proprietary Information. Information that constitutes a trade secret or other confidential commercial or financial information.

Prototype. A model of something to be further developed, which includes designs, protocols, questionnaires, software, and devices.

SBIR Participants. Business concerns that have received SBIR awards or that have submitted SBIR proposals/applications.

SBIR Technical Data. All data generated during the performance of an SBIR award.

SBIR Technical Data Rights. The rights an SBIR awardee obtains in data generated during the performance of any SBIR

Phase I, Phase II, or Phase III award that an awardee delivers to the Government during or upon completion of a Federally-funded project, and to which the Government receives a license.

Service-Disabled Veteran-Owned Small Business Concern. A small business concern note less than 51 percent of which is owned by one or more service-disabled veterans or, in the case of any publicly owned business, not less than 51 percent of the stock of which is owned by one or more service-disabled veterans; and, the management and daily business operations of which are controlled by one or more service-disabled veterans or, in the case of a service-disabled veteran with permanent and severe disability, the spouse or permanent caregiver of such a veteran. Service-disabled veteran means a veteran, as defined in 38 U.S.C. 101(2), with a disability that is service-connected, as defined in 38 U.S.C. 101(16).

Small Business Concern (SBC). A concern that meets the requirements set forth in 13 CFR 121.702:

To be eligible for award of funding agreements in the SBA's Small Business Innovation Research (SBIR) program, a business concern must meet the requirements of paragraphs (a) and (b) below:

(a) Ownership and control.

(1) An SBIR awardee must:

(i) 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 small 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 (Alaska Native Corporation) or NHO (Native Hawaiian

Organization) (or a wholly owned business entity of such tribe, ANC or NHO), or any combination of these; OR

(ii) 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 (for agencies electing to use the authority in 15

U.S.C. 638(dd)(1)); OR

(iii) Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph (a)(1)(i) or (a)(1)(ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (a)(1)(ii) of this section must comply with § 121.705(b) concerning registration and proposal requirements

(2) No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern.

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

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

(b) Size. An SBIR awardee, together with its affiliates, will not have more than 500 employees.

http://www.ecfr.gov/cgi-bin/text-idx?SID=ddf55574cd923f5ebaefd02bf517d956&mc=true&node=se13.1.121_1702&rgn=div8

Small Disadvantaged Business Concern. Consistent with 13 CFR 124.1002, means a small business concern under the size standard applicable to the acquisition, that: is at least 51 percent unconditionally and directly owned (as defined at 13 CFR

124.105) by one or more socially disadvantaged (as defined at 13 CFR 124.103) and economically disadvantaged (as defined at 13 CFR 124.104) individuals who are citizens of the United States; and, each individual claiming economic disadvantage has a net worth not exceeding $750,000 after taking into account the applicable exclusions set forth at 13 CFR 124.104(c)(2);

and, the management and daily business operations of which are controlled (as defined at 13 CFR 124.106) by individuals who meet the criteria in paragraphs (1)(i) and (ii) of this definition.

Socially and Economically Disadvantaged Individual. See 13 CFR 124.103 and 124.104.

Subcontract. Any agreement, other than one involving an employer-employee relationship, entered into by an awardee of a funding agreement calling for supplies or services for the performance of the original funding agreement.

United States. Means the 50 states, the territories and possessions of the Federal Government, the Commonwealth of Puerto

Rico, the District of Columbia, the Republic of the Marshall Islands, the Federated States of Micronesia, and the Republic of

Palau.

Women-Owned Small Business Concern. A small business concern that is at least 51% owned by one or more women, or in the case of any publicly owned business, at least 51% of the stock is owned by women, and women control the management and daily business operations.

3.2 Definitions (Relating to R&D)

Autopsy Materials. The use of autopsy materials is governed by applicable Federal, state, and local law and is not directly regulated by 45 CFR part 46.

Child. The NIH Policy on Inclusion of Children defines a child as an individual under the age of 18 years

(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-010.html). The intent of the NIH policy is to provide the opportunity for children to participate in research studies when there is a sound scientific rationale for including them, and their participation benefits children and is appropriate under existing Federal guidelines. Thus, children must be included in

NIH conducted or supported clinical research unless there are scientific or ethical reasons not to include them. This policy is separate from considerations of protections and consent for children to participate in research.

Clinical Research. NIH defines human clinical research as research with human subjects that is:

(1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects.

Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual.

Patient-oriented research includes:

(a) mechanisms of human disease,

(b) therapeutic interventions,

(c) clinical trials, or

(d) development of new technologies.

(2) Epidemiologic and behavioral studies.

(3) Outcomes research and health services research.

Note: Studies falling under Exemption 4 for human subjects research are not considered clinical research by this definition.

Clinical Trial. NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

If the answers to all four questions below are yes, the study meets the definition of a Clinical Trial:

- Does the study involve human participants?

http://www.ecfr.gov/cgi-bin/text-idx?SID=ddf55574cd923f5ebaefd02bf517d956&mc=true&node=se13.1.124_1103&rgn=div8 http://www.ecfr.gov/cgi-bin/text-idx?SID=ddf55574cd923f5ebaefd02bf517d956&mc=true&node=se13.1.124_1104&rgn=div8 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-010.html

- Are the participants prospectively assigned to an intervention?

- Is the study designed to evaluate the effect of the intervention on the participants?

- Is the effect that will be evaluated a health-related biomedical or behavioral outcome?

See Appendix H.1 Instructions, Human Subjects and Clinical Trials Information Form, Section 1.4. Clinical Trial

Questionnaire, for further information and references for understanding this definition. Appendix H.1. is located in Section

12 – Appendices of this solicitation.

Human Subjects. The HHS regulations “Protection of Human Research Subjects” 45 CFR part 46, (administered by OHRP) define a human subject as a living individual about whom an investigator conducting research obtains:

• Data through intervention or interaction with the individual; or,

• Identifiable private information.

Individually Identifiable Private Information. According to its guidance for use of coded specimens, OHRP generally considers private information or specimens to be individually identifiable as defined at 45 CFR 46.102(f) when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. Conversely, OHRP considers private information or specimens not to be individually identifiable when they cannot be linked to specific individuals by the investigator(s) either directly or indirectly through coding system.

Interaction includes communication or interpersonal contact between investigator and subject. (45 CFR 46.102(f)).

Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. (45 CFR 46.102(f)).

Investigational Device Exemption (IDE). An IDE is a regulatory submission that permits clinical investigation of devices.

This investigation is exempt from some regulatory requirements. The term “IDE” stems from the description in 21 CFR

812.1.

Investigator. The OHRP considers the term investigator to include anyone involved in conducting the research. OHRP does not consider the act of solely providing coded private information or specimens (for example, by a tissue repository) to constitute involvement in the conduct of the research. However, if the individuals who provide coded information or specimens also collaborate on other activities related to the conduct of the research with the investigators who receive such information or specimens, they will be considered to be involved in the conduct of the research. (See OHRP’s Guidance on

Research Involving Coded Private Information on Biological Specimens.)

Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects. (45 CFR 46.102(f))

• Coded. With respect to private information or human biological specimens, coded means that:

o Identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol or combination thereof (i.e., the code); and o A key to decipher the code exists, enabling linkage of the identifying information with the private information or specimens.

Research that involves only coded private information/data or coded human biological specimens may not constitute human subjects research under the HHS human subjects regulations (45 CFR 46) if:

○ The specimens and/or information/data are not obtained from an interaction/intervention with the subject specifically for the research; and

○ The investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain (e.g., the researcher's access to subject identities is prohibited).

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html http://www.hhs.gov/ohrp/policy/cdebiol.html http://www.hhs.gov/ohrp/policy/cdebiol.html

Individuals who provide coded information or specimens for proposed research and who also collaborate on the research involving such information or specimens are considered to be involved in the conduct of human subjects research.

(See the following guidance from the Office for Human Research Protections (OHRP) for additional information and examples: http://www.hhs.gov/ohrp/policy/cdebiol.html.)

Research or Research and Development (R/R&D). Any activity that is:

• A systematic, intensive study directed toward greater knowledge or understanding of the subject studied;

• A systematic study directed specifically toward applying new knowledge to meet a recognized need; or

• A systematic application of knowledge toward the production of useful materials, devices, and systems or methods, including design, development, and improvement of prototypes and new processes to meet specific requirements.

Research Involving Vertebrate Animals

All research involving live vertebrate animals shall be conducted in accordance with the Public Health Service Policy on

Humane Care and Use of Laboratory Animals (PHS Policy).

In addition, the research involving live vertebrate animals shall be conducted in accordance with the description set forth in the Vertebrate Animal Section (VAS) of the contractor's technical proposal, as modified in the Final Proposal Revision

(FPR), which is incorporated by reference. If using live vertebrate animals, HHS policy requires that offerors address the criteria in the Vertebrate Animal Section (VAS) of the Technical Proposal. Each of the criteria must be addressed in the VAS portion of the Technical Proposal. For additional information see Office of Laboratory Animal Welfare – Vertebrate Animals

Section and use Contract Proposal VAS Worksheet. .

Research Involving Human Subjects: All research involving human subjects, to include use of identifiable human biological specimens and human data, shall comply with the applicable federal and state laws and agency policy/guidelines for human subject protection.

Exemptions. The following six categories of research meet the basic definition of human subjects research but are considered to be exempt from the HHS human subject regulations:

(1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as:

(i) Research on regular and special education instructional strategies; or

(ii) Research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

(2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:

(i) Information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and

(ii) Any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.

(3) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if:

(i) The human subjects are elected or appointed public officials or candidates for public office; or

(ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

http://www.hhs.gov/ohrp/policy/cdebiol.html http://grants1.nih.gov/grants/olaw/references/phspol.htm http://grants.nih.gov/grants/olaw/vertebrate_animal_section.htm http://grants.nih.gov/grants/olaw/vertebrate_animal_section.htm http://grants.nih.gov/grants/olaw/VAScontracts.pdf

(4) Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

(5) Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine:

(i) Public benefit or service programs;

(ii) Procedures for obtaining benefits or services under those programs;

(iii) Possible changes in or alternatives to those programs or procedures; or

(iv) Possible changes in methods or levels of payment for benefits or services under those programs.

(6) Taste and food quality evaluation and consumer acceptance studies,

(i) If wholesome foods without additives are consumed or

(ii) If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and

Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection

Service of the U.S. Department of Agriculture.

See Appendix H.1 Instructions, Human Subjects and Clinical Trials Information Form, Section 1.3. Exemption Number, for additional guidance. Appendix H.1. can be located in Section 12 – Appendices of this solicitation.

Research Involving Recombinant or Synthetic Nucleic Acid Molecules. Any recipient performing research involving recombinant or synthetic nucleic acid molecules and/or organisms and viruses containing recombinant or synthetic nucleic acid molecules shall comply with the National Institutes of Health Guidelines for Research Involving Recombinant or

Synthetic Nucleic Acid Molecules, dated April 2016 as amended. The guidelines can be found at:

https://www.federalregister.gov/documents/2016/04/15/2016-08810/national-institutes-of-health-nih-office-of-science-policy-osp-recombinant-or-synthetic-nucleic-acid.

Recombinant or synthetic nucleic acid molecules are defined as:

(i) Molecules that a) are constructed by joining nucleic acid molecules and b) that can replicate in a living cell, i.e., recombinant nucleic acids;

(ii) Nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules, i.e., synthetic nucleic acids; or,

(iii) Molecules that result from the replication of those described in (i) or (ii) above.

Sex/Gender. Refers to the classification of research subjects in either or both of two categories: male and female. In some cases, representation is unknown, because sex/gender composition cannot be accurately determined (e.g. pooled blood samples or stored specimens without sex/gender designation). In addition, sex/gender classification is based on the self-reporting of participants enrolled in the research study. Investigators should consider the scientific goals of their study when requesting this information, particularly if the research may include individuals whose gender identity differs from their sex assigned at birth.

Valid Analysis. This term means an unbiased assessment. Such an assessment will, on average, yield the correct estimate of the difference in outcomes between two groups of subjects. Valid analysis can and should be conducted for both small and large studies. A valid analysis does not need to have a high statistical power for detecting a stated effect. The principal requirements for ensuring a valid analysis of the question of interest are: allocation of study participants of both sexes/genders (males and females) and from different racial and/or ethnic groups to the intervention and control groups by an unbiased process such as randomization; unbiased evaluation of the outcome(s) of study participants; and use of unbiased statistical analyses and proper methods of inference to estimate and compare the intervention effects by sex/gender, race, and/or ethnicity.

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4 PROPOSAL FUNDAMENTALS

4.1 Introduction

The proposal must provide sufficient information to demonstrate to the evaluator(s) that the proposed work represents an innovative approach to the investigation of an important scientific or engineering problem and is worthy of support under the stated criteria. The proposed research or research and development must be responsive to the topic area. Anyone contemplating a proposal should determine that: (a) the technical approach has a reasonable chance of meeting the topic objective; (b) this approach is innovative, not routine, with potential for commercialization; and, (c) the proposing firm has the capability to implement the technical approach, i.e., has or can obtain people and equipment suitable to the task.

4.2 Offeror Eligibility and Performance Requirements

To receive SBIR funds, each awardee must qualify as a small business concern (SBC) at the time of award and at any other time set forth in SBA's regulations at 13 CFR 121.701-121.705. Each applicant must qualify as a small business for research or research and development purposes and certify to this on the Cover Sheet of the proposal. Additionally, each awardee must submit a certification stating that it meets the size, ownership and other requirements of the SBIR Program at the time of award, and at any other time set forth in SBA's regulations at 13 CFR 121.701-705.

A minimum of two-thirds of the research or analytical effort must be performed by the awardee.

The percentage of work will be measured by total contract costs.

The principal investigator must be primarily employed with the SBC. Primary employment means that more than one half (50%) of the employee's time is spent with the small business. Primary employment with the SBC precludes full-time employment at another organization.

All research or research and development work must be performed by the SBC and its subcontractors in the

United States.

Based on rare and unique circumstances, deviations from these performance requirements may occur, and must be approved in writing by the funding agreement officer after consultation with the agency SBIR Program

Manager/Coordinator.

4.3 SBIR/STTR Performance…