PHS2014-1_Final.pdf

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES (HHS), THE

NATIONAL INSTITUTES OF HEALTH (NIH) AND THE CENTERS FOR

DISEASE CONTROL AND PREVENTION (CDC) SMALL BUSINESS

INNOVATIVE RESEARCH (SBIR) PROGRAM

PROGRAM SOLICITATION PHS 2014-1

Closing Date: November 13, 2013, 4:30PM Eastern Time

Participating HHS Components:

● The National Institutes of Health (NIH)

● The Centers for Disease Control and Prevention (CDC)

IMPORTANT

Deadline for Receipt: Proposals must be submitted by November 13, 2013, 4:30PM Eastern Time

Solicitation Changes:

As a result of program reauthorization, the solicitation has been EXTENSIVELY rewritten and follows the changes of the SBIR/STTR reauthorization. Please read the entire solicitation carefully prior to submitting your proposal.

Please go to http://www.sbir.gov/about/sbir-policy-directive to read the SBIR/STTR Policy Directive issued by the Small Business Administration.

http://www.sbir.gov/about/sbir-policy-directive ii

Table of Contents

1 INTRODUCTION

2 PROGRAM DESCRIPTION

2.1 Objectives

2.2 Three Phase Program

2.3 Grant Opportunity - Phase IIB Competing Renewal Awards (INFORMATION ONLY)

2.4 Awarding Components

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 Multiple Principal Investigators

4.4 Joint Ventures

4.5 Majority Ownership in Part by Multiple Venture Capital, Hedge Fund, and Private Equity Firms (NIH

COMPONENTS ONLY)

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

COMPONENTS ONLY)

4.7 Conflicts of Interest

4.8 Market Research

4.9 OMB Clearance

4.10 Research Involving Human Subjects

4.11 Care of Live Vertebrate Animals

4.12 Research Involving Recombinant DNA Molecules

4.13 Debriefing

4.14 Phase I Award and (FAST TRACK NIH ONLY) Information

4.15 Phase II/FAST TRACK Award Information

4.16 Registrations and Certifications

4.17 Promotional Materials

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

4.19 Fraud and False Statements

4.20 State and Other Assistance Available

4.21 Payment

4.22 Proprietary Information

4.23 Identification and Marking of SBIR Technical Data in Proposals

5 CONTRACT REQUIREMENTS

5.1 Other Contract Requirements

5.2 Special Contract Requirements

5.3 Copyrights

5.4 Patents

5.5 Technical Data Rights

5.6 Invention Reporting

6 METHOD OF EVALUATION

iii

6.1 Evaluation Process

6.2 Phase I Technical Evaluation Criteria

6.3 FAST TRACK (NIH ONLY)/Phase II Technical Evaluation Criteria Evaluation Criteria

6.4 Award Decisions

7 PROPOSAL SUBMISSION

7.1 Limitation on the Length of the Technical Proposal

7.2 Submission, Modifications, Revision, and Withdrawal of Proposals

7.3 How To Submit Proposals

8 PROPOSAL PREPARATION AND INSTRUCTIONS

8.1 Introduction

8.2 Phase I Proposal Instructions

8.3 Fast Track Proposal Instructions

8.4 Human Subjects Research and Protection from Risk

8.5 Research Involving Prisoners as Subjects

8.6 Research Involving Human Fetal Tissue

8.7 Research Involving Live Vertebrate Animals

8.8 Content of the Pricing Proposal (Item Two)

8.9 Proposal Checklists

9 SUMMARY OF HHS COMPONENTS ANTICIPATED NUMBER OF AWARDS

10 CONTRACTING OFFICERS AND ADDRESSES FOR DELIVERY OF CONTRACT PROPOSALS

National Institutes of Health (NIH)

National Cancer Institute (NCI) National Center for Advancing Translational Sciences (NCATS) National Heart, Lung, and Blood Institute (NHLBI) National Institute on Aging (NIA) National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institute of Allergy and Infectious Diseases (NIAID) National Institute on Drug Abuse (NIDA)

Centers for Disease Control and Prevention (CDC)

Center for Global Health (CGH) National Center for Birth Defects and Developmental Disabilities (NCBDDD) National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) National Center for Emerging Zoonotic and Infectious Diseases (NCEZID) National Center for HIV/AIDs, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) National Center for Immunization and Respiratory Diseases (NCIRD) Office of Public Health Preparedness and Response (OPHPR)

11 SCIENTIFIC AND TECHNICAL INFORMATION SOURCES

12 COMPONENT INSTRUCTIONS AND TECHNICAL TOPIC DESCRIPTIONS

National Institutes of Health

National Cancer Institute (NCI)

326 Development of Novel Therapeutic Agents that Target Cancer Stem Cells 327 Reformulation of Failed Chemotherapeutic Drugs iv

328 Validation of 3D Human Tissue Culture Systems that Mimic the Tumor Microenvironment

329 Proteomic Analysis of Single Cells Isolated from Solid Tumors 330 Generation of Site-Specific Phospho-Threonine Protein Standards for use in Cancer

Assays 331 Development of a Biosensor-Based Core Needle Tumor Biopsy Device 332 Development of Radiation Modulators for Use During Radiotherapy 333 Software Tools for the Development of Environmental Measures Related to Cancer

Health Behaviors and Resources

National Center for Advancing Translational Sciences (NCATS)

005 Development of biomarkers for rare diseases as endpoints for clinical trial measurements74 006 Development of Neurocognitive Pediatric Tools for Measuring and Analyzing Clinical

Study Endpoints in Rare Neurocognitive Disorders 007 Exploring the Potential of CRISPR/CAS Genome-editing Tools 008 Droplet Detection System

National Heart, Lung, and Blood Institute (NHLBI)

081 Passive MRI Cardiovascular Guidewire 082 MRI Myocardial Needle Injection Catheter 083 Transcatheter Pulmonary Artery Resistor 084 Value of Information Models for Clinical Trial Assessment 085 Development of Molecular Imaging Agents and Methods to Detect High Risk

Atherosclerotic Plaque 086 Tools for Educating Children about Clinical Research

National Institute on Aging (NIA)

087 Development of Calorie-restricted and Nutrient-balanced Medicinal Food Products for Mitigation of Age-related Diseases or Conditions

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

088 Development of a Database of Non-English Measures and Instruments for Use in Alcohol Research

National Institute of Allergy and Infectious Diseases (NIAID)

025 Biomedical Methods To Quantify Adherence To Prevention Clinical Trial Study Products and Strategies

026 Simple, Inexpensive Assay for Five Common HIV Resistance Mutations 027 Capreomycin: Formulation for Oral Delivery 028 Adjuvant Development

National Institute on Drug Abuse (NIDA)

151 Web Resource System for Prescription Drug Providers, Researchers and Users: The Prescription Drug Abuse Policy System (PDAPS)

152 Technological Tools to Facilitate Implementation of Evidence-Based Substance Abuse Prevention Interventions among the Military

153 Products to Prevent (Lethal) Drug-induced Respiratory Depression 154 Bundled Service for Designing Methodologically Rigorous Animal Studies v

155 Affordable Care Act (ACA) Web Platform to Integrate Behavioral Health & Prevention with Primary Care

Centers for Disease Control and Prevention (CDC)

Center for Global Health (CGH)

006 Development of Novel Malaria Parasite Metabolite-based Non-invasive Diagnostic Biosensor

National Center on Birth Defects and Developmental Disabilities (NCBDDD)

018 Developing Rapid Test for the Diagnosis of Sickle Cell Disease 019 Development of Rapid, Point-of-care Tests for Cytomegalovirus (CMV) 020 Nutrition Support for Group Homes Serving Individuals with Intellectual Disabilities . 115

National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)

034 Promoting Regular Physical Activity for Older Adults through “Wayfinding” Technology117 035 Development of Pills or Tablets to Expedite Water Fluoridation 036 Application for Improving Embryo Transfer Practices at Fertility Clinics

National Center for Emerging Zoonotic and Infectious Diseases (NCEZID)

006 Distinguishing Infection, Colonization, and Recurrence in Patients with Clostridium difficile

007 Development of Reagents for Diagnosis of Fungal Infections in Formalin-fixed Paraffinized (FFPE) Tissue Blocks

008 Rapid Detection of Endemic Fungal Infections in the United States 009 Development of Anti-Japanese Encephalitis Virus Human Monoclonal Antibodies Using

Humanized Rodent Models 010 Formulation of Nootkatone in Soaps and Lotions for Lyme Disease Prevention

National Center for HIV/AIDs, Viral Hepatitis, STD, and TB Prevention (NCHHSTP)

037 Development of a Rapid Test for detection hepatitis C core antigen in clinical samples.124 038 Development of a Laboratory Test for Detection of Serum Biomarkers Associated with

Hepatocellular Carcinoma 039 Text my EOB: The Innovative Delivery of Confidential Medical Information 040 Development of a Mobile Application for Homeless Youth and Providers 041 Leveraging Technology to Prevent STIs Using High-Intensity Behavioral Counseling 129 042 Assessing the Feasibility of e-measure Adoption in an EHR Environment

National Center for Immunization and Respiratory Diseases (NCIRD)

027 Thermostable Dry Vaccine Formulation for Microneedle Administration 028 Development of Anti-diphtheria Antibodies for Use in Humans

Office of Public Health Preparedness and Response (OPHPR)

003 “Plug and Play” Global Health Security Initiative (GHSI) Response Tool 004 Improved Rapid Antimicrobial Susceptibility Testing from Primary Specimens

13 APPENDICIES

APPENDIX A — PROPOSAL COVER SHEET - USE FOR PHASE I AND FAST-TRACK PROPOSALS

vi

APPENDIX B — ABSTRACT OF RESEARCH PLAN - USE FOR PHASE I, PHASE II, AND FAST-TRACK

PROPOSALS

APPENDIX C — PRICING PROPOSAL - USE FOR PHASE I, PHASE II AND FAST-TRACK PROPOSALS 135 APPENDIX D — PHASE II TECHNICAL PROPOSAL COVER SHEET - USE FOR PHASE II AND FAST-

TRACK PROPOSALS

APPENDIX E — STATEMENT OF WORK SAMPLE FORMAT - USE FOR PHASE II AND FAST-TRACK

PROPOSALS

APPENDIX F — SUMMARY OF RELATED ACTIVITIES - USE FOR PHASE II AND FAST- TRACK

PROPOSALS

APPENDIX G — PROPOSAL SUMMARY AND DATA RECORD - USE FOR PHASE II AND FAST-TRACK

PROPOSALS

1 INTRODUCTION

The National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) invite 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 any of the health related topic areas described in Section 12.0, and to commercialize the results of that R&D, are encouraged to participate.

While the Phase II proposal process is covered in this announcement, this solicitation is for Phase I, and in some cases, FAST TRACK proposals only. Some NIH Components utilize a contract mechanism called FAST TRACK which allows for the simultaneous submission of Phase I and Phase II proposals for review and possible award of Phase I with an option for Phase II work. FAST TRACK PROPOSALS WILL ONLY BE SUBMITTED UNDER THE

FOLLOWING TOPICS AND ALL OTHER PHASE II PROPOSALS WILL NOT BE CONSIDERED.

TOPIC NUMBER TOPIC TITLE FOR FAST TRACK PROPOSALS

NCI 327 Reformulation of Failed Chemotherapeutic Drugs

NCI 328 Validation of 3D Human Tissue Culture Systems that Mimic the Tumor Microenvironment

NCI 329 Proteomic Analysis of Single Cells Isolated from Solid Tumors

NCI 330 Generation of Site-Specific Phospho-Threonine Protein Standards for use in Cancer Assays

NCI 331 Development of a Biosensor-Based Core Needle Tumor Biopsy Device

NCI 332 Development of Radiation Modulators for Use During Radiotherapy

NCI 333 Software Tools for the Development of Environmental Measures Related to Cancer Health Behaviors and Resources

NHLBI 081 Passive MRI Cardiovascular Guidewire

NHLBI 082 MRI Myocardial Needle Injection Catheter

NHLBI 083 Transcatheter Pulmonary Artery Resistor

NHLBI 084 Value of Information Models for Clinical Trial Assessment

NHLBI 085 Development of Molecular Imaging Agents and Methods to Detect High Risk Atherosclerotic Plaque

NHLBI 086 Tools for Educating Children about Clinical Research

NIA 087 Development of Calorie-restricted and Nutrient-balanced Medicinal Food Products for Mitigation of Age-related Diseases or Conditions

NIAAA 045 Development of a Database of Non-English Measures and Instruments for Use in Alcohol Research

NIDA 152 Technological Tools to Facilitate Implementation of Evidence-Based Substance Abuse Prevention Interventions among the Military

NIDA 153 Products to Prevent (Lethal) Drug-induced Respiratory Depression

NIDA 154 Bundled Service for Designing Methodologically Rigorous Animal Studies All firms that are awarded Phase I contracts originating from this solicitation will be eligible to participate in Phases II and III. HHS Components will notify Phase I awardees of the Phase II proposal submission requirements. Submission of Phase II proposals will be in accordance with dates provided by individual Component instructions. The details on the due date, content, and submission requirements of the Phase II proposal will be provided by the awarding HHS Component either in the Phase I award or by subsequent notification. All SBIR/STTR Phase II awards made on topics from solicitations prior to FY13 will be conducted in accordance with the procedures specified in those solicitations.

The HHS is not obligated to make any awards under Phase I, Phase II, or Phase III, and 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.

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 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 NIH/CDC SBIR program is in accordance with the Small Business Administration (SBA) SBIR Program Policy Directive dated October 18, 2012. This SBIR Contract solicitation strives to encourage scientific and technical innovation in areas specifically identified by the NIH/CDC awarding components. 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 NIH/CDC and to the private sector.

2.2 Three Phase Program

The SBIR program consists of three separate phases. The award amount and duration listed below represent the guidelines of the SBIR program and, unless the research topic stating the award listed in Section 12.0 of the solicitation states otherwise.

Phase I: Feasibility; $150,000; 6 months (See Section 12.0 for Specific Award amounts per Topic Number)

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 I awards normally may not exceed $150,000 for direct costs, indirect costs, and profit (fixed fee) for a period normally not to exceed 6 months.

Phase II: Full R/R&D Effort; $1,000,000; 2 years

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 II awards normally may not exceed $1,000,000 for direct costs, indirect costs, and profit (fixed fee) for a period normally not to exceed two years. Phase I contractors will be informed of the opportunity to apply for Phase II, if not submitted concurrently with the initial Phase I proposal under the Fast-Track procedure. Only one Phase II award may result from a single Phase I SBIR contract.

FAST TRACK (NIH COMPONENTS ONLY) - See Research Topics for Specific award amounts/period of performance

The “Fast-Track” initiative is a parallel review option available to those small business concerns (offeror organizations) whose proposals satisfy additional criteria that enhance the probability of the project's commercial success. This initiative is applicable only to NIH and only if an awarding component indicates it is accepting Fast-Track proposals for a particular topic. (Refer to Section 12.0 “Research Topics,” for notation.)

Phase III: Commercialization stage without SBIR funds

The objective of Phase III, where appropriate, 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 involve follow-on, non-SBIR funded R&D or production contracts for products or processes intended for use by the U.S.

Government.

The competition for SBIR Phase I and Phase II awards satisfies any competition requirement of the Armed Services Procurement Act, the Federal Property and Administrative Services Act, and the Competition in Contracting Act. Therefore, an agency that wishes to fund an SBIR Phase III project is not required to conduct another competition in order to satisfy those statutory provisions. As a result, in conducting actions relative to a Phase III SBIR award, it is sufficient to state for purposes of a Justification and Approval pursuant to FAR 6.302-5 that the project is a SBIR Phase III award that is derived from, extends, or logically concludes efforts performed under prior SBIR funding agreements and is authorized under 10 U.S.C. 2304(b)(2) or 41 U.S.C. 253(b)(2).

The NIH is interested in developing products and services via the SBIR program that improve the health of the American people. In its commitment to also support Executive Order 13329, encouraging innovation in manufacturing-related research and development, NIH seeks, through the SBIR program, biomedical research related to advanced processing, manufacturing processes, equipment and systems; or manufacturing workforce skills and protection. This solicitation includes some topic areas that are considered relevant to manufacturing-related R&D. Additional information will be posted on the NIH Small Business Research Funding Opportunities Web site and in the NIH Guide for Grants and Contracts as it becomes available.

Small businesses may be interested in reading a U.S. Department of Commerce 2004 report, "Manufacturing in America: A Comprehensive Strategy to Address the Challenges to U.S. Manufacturers".

2.3 Grant Opportunity - Phase IIB Competing Renewal Awards (INFORMATION ONLY)

Some NIH Institutes/Centers (ICs) offer Phase II SBIR/STTR awardees the opportunity to apply for Phase IIB Competing Renewal awards. These are available for those projects that require extraordinary time and effort in the R&D phase and may or may not require FDA approval for the development of such projects, including drugs, devices, vaccines, therapeutics, and medical implants related to the mission of the IC. Some ICs have announced this opportunity through the NIH Guide for Grants and Contracts (see link below), and some are using this Omnibus SBIR/STTR Grant Solicitation. Only those small business concerns who have been awarded a Phase II are eligible to apply for a Phase IIB Competing Renewal award.

Prospective applicants are strongly encouraged to contact NIH staff prior to submission. Additional requirements and instructions (e.g., submission of a letter of intent) are available in the specific IC research topics section and in the specific IC Program Funding Opportunity Announcements . The following NIH ICs will accept applications for Phase IIB Competing Renewal awards: NIA, NIAAA, NIAID (SBIR only), NICHD (SBIR only and only Competing Renewals of NICHD-supported Phase II awards), NIDA, NIDCD, NIDDK (only Competing Renewals of NIDDK-supported Phase II awards), NEI (SBIR only), NIGMS (SBIR only), NIMH (SBIR only), NCATS (SBIR only), and ORIP (SBIR only). NCI offers Phase IIB opportunities that focus on the commercialization of SBIR-developed technologies. Contact the NCI SBIR Development Center at 240-276-5300, NCISBIR@mail.nih.gov for additional information. NHLBI offers Phase IIB Competing Renewals that focus on the commercialization of technologies requiring regulatory approval through the NHLBI Bridge Award (RFA- HL-13-016) and the NHLBI Small Market Award (RFA-HL-14-012). Contact Kurt Marek, Ph.D., at 301-443-8778 or kurt.marek@nih.gov for additional information. NINDS accepts Phase IIB SBIR/STTR Competing Renewal applications through specific opportunities that focus on the commercialization of SBIR and STTR developed technologies. These opportunities can be found on the NINDS SBIR webpage: http://www.ninds.nih.gov/funding/small-business/small_business_funding_opportunities.htm. Contact Stephanie Fertig, M.B.A., at 301-496-1779 or fertigs@ninds.nih.gov for additional information.

2.4 Awarding Components

The following awarding components are participating in this SBIR Solicitation for Contract Proposals.

National Institutes of Health (NIH) Components:

National Cancer Institute (NCI)

National Center for Advancing Translational Sciences (NCATS)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute on Drug Abuse (NIDA) http://www.gpo.gov/fdsys/pkg/FR-2004-02-26/pdf/04-4436.pdf http://grants.nih.gov/grants/funding/sbir.htm http://grants.nih.gov/grants/funding/sbir.htm http://grants.nih.gov/grants/guide/ http://www.nist.gov/tpo/sbir/upload/DOC_MFG_Report_Complete-2.pdf http://www.nist.gov/tpo/sbir/upload/DOC_MFG_Report_Complete-2.pdf http://grants.nih.gov/grants/funding/sbir_announcements.htm http://grants.nih.gov/grants/funding/sbir_announcements.htm mailto:NCISBIR@mail.nih.gov mailto:kurt.marek@nih.gov http://www.ninds.nih.gov/funding/small-business/small_business_funding_opportunities.htm http://www.ninds.nih.gov/funding/small-business/small_business_funding_opportunities.htm mailto:fertigs@ninds.nih.gov

Centers for Disease Control and Prevention (CDC) Components:

Center for Global Health (CGH)

National Center for Birth Defects and Developmental Disabilities (NCBDDD)

National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)

National Center for Emerging Zoonotic and Infectious Diseases (NCEZID)

National Center for HIV/AIDs, Viral Hepatitis, STD, and TB Prevention (NCHHSTP)

National Center for Immunization and Respiratory Diseases (NCIRD)

Office of Public Health Preparedness and Response (OPHPR)

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) Small Business Concern. A small business concern that is owned and controlled by a socially and economically disadvantaged individual and that has been approved by the U.S. Small Business Administration as part of the 8(a) Business Development Program (see 13 CFR 124).

Act. The Small Business Act (15 U.S.C. 631, et seq.), as amended.

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. What is affiliation? (Available at http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr;sid=03878acee7c064a02cac0d870e00ef43;rgn=div6;view=text;node=13%3A1.0.1.1.17.1;idno=13;cc=ecfr.)

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

Awardee. The organizational entity receiving an SBIR Phase I, Phase II, or Phase III 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, grantees 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.

Cooperative Agreement. A financial assistance mechanism used when substantial Federal programmatic involvement with the awardee during performance is anticipated by the issuing agency. The Cooperative Agreement contains the responsibilities and respective obligations of the parties.

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.

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.

Extramural Budget. The sum of the total obligations for R/R&D minus amounts obligated for R/R&D activities by employees of a Federal agency in or through Government-owned, Government-operated facilities. For the Agency for http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&sid=ce3e916e1e4b3996dd3202b046326260&tpl=/ecfrbrowse/Title13/13cfr124_main_02.tpl http://www.gpo.gov/fdsys/granule/USCODE-2011-title15/USCODE-2011-title15-chap14A-sec631/content-detail.html http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr;sid=03878acee7c064a02cac0d870e00ef43;rgn=div6;view=text;node=13%3A1.0.1.1.17.1;idno=13;cc=ecfr http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr;sid=03878acee7c064a02cac0d870e00ef43;rgn=div6;view=text;node=13%3A1.0.1.1.17.1;idno=13;cc=ecfr https://rippleeffect.sharepoint.com/projects/OPERA/SBIRSTTR_Support/Archive/2013-08%20PHS2014-1%20Contract%20Solicitation/www.SBIR.gov http://www.sba.gov/size

International Development, the “extramural budget” must not include amounts obligated solely for general institutional support of international research centers or for grants to foreign countries. For the Department of Energy, the “extramural budget” must not include amounts obligated for atomic energy defense programs solely for weapons activities or for naval reactor programs. (Also see section 7(i) of this Policy Directive for additional exemptions related to national security.)

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

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

a. 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.

b. 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.

c. 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 Small Business Concerns maintained by the Small Business Administration (13 CFR 126.103). HUBZone Small Business Concerns are located in historically underutilized business zones, in an effort to increase employment opportunities, investment, and economic development in those areas.

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.

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. See 13 CFR 121.103(h).

Key Individual. The principal investigator/project manager and any other person named as a “key” employee in a proposal submitted in response to a program solicitation.

http://www.gpo.gov/fdsys/granule/USCODE-2011-title5/USCODE-2011-title5-partI-chap1-sec102/content-detail.html http://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=7528966d1b7a86b5bf5f3b5952fcca63&r=PART&n=13y1.0.1.1.17#13:1.0.1.1.17.1.267.3

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. Announcements in the Federal Register or the GPE are not considered an SBIR Program solicitation.

Proprietary Information. Proprietary information is information that you provide which constitutes a trade secret, proprietary commercial or financial information, confidential personal information or data affecting the national security.

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.

Senior/Key Personnel. The PD/PI and other individuals who contribute to the scientific development or execution of the project in a substantive, measurable way, whether or not salaries or compensation are requested under the contract.

Small Business Concern. 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 business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these; 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. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern;

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 (ii) of this section must comply with § 121.705(b) concerning registration and proposal requirements

(2) If an Employee Stock Ownership Plan owns all or part of the concern, SBA considers each stock trustee and plan member to be an owner.

(3) If a trust owns all or part of the concern, SBA considers each trustee and trust beneficiary to be an owner.

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

Socially and Economically Disadvantaged SBC (SDB). See 13 CFR part 124, Subpart B.

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

Service-Disabled Veteran-Owned Small Business Concern. A small business concern not 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 veteran. Status as a Service-Disabled Veteran-Owned Small Business Concern is determined in accordance with 13 CFR Parts 125.8 through 125.13; also see 19.307.

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 SBC (WOSB). An SBC 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 21 years. 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.

HHS Regulations (45 CFR part 46, Subpart D, Sec.401-409) provide additional protections for children involved as subjects in research, based on this definition: "Children are persons who have not attained the legal age for consent to treatments or procedures involved in research, under the applicable law of the jurisdiction in which the research will be conducted."

Generally, state laws define what constitutes a “child.” Consequently, the age at which a child's own consent is required and sufficient to participate in research will vary according to state law. For example, some states consider a person age 18 to be an adult and therefore one who can provide consent without parental permission.

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 studies, or

(d) development of new technologies.

(2) Epidemiologic and Behavioral Studies.

(3) Outcomes Research and Health Services Research.

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Clinical Trial. The NIH defines a clinical trial as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices).

Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective.

Behavioral human subjects research involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fits this definition of a clinical trial.

Human subjects research to develop or evaluate clinical laboratory tests (e.g. imaging or molecular diagnostic tests) might be considered to be a clinical trial if the test will be used for medical decision making for the subject or the test itself imposes more than minimal risk for subjects.

Biomedical clinical trials of experimental drug, treatment, device or behavioral intervention may proceed through four phases:

○ Phase I clinical trials test a new biomedical intervention in a small group of people (e.g., 20-80) for the first time to evaluate safety (e.g., to determine a safe dosage range and to identify side effects).

○ Phase II clinical trials study the biomedical or behavioral intervention in a larger group of people (several hundred) to determine efficacy and to further evaluate its safety.

○ Phase III studies investigate the efficacy of the biomedical or behavioral intervention in large groups of human subjects (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the intervention to be used safely.

○ Phase IV studies are conducted after the intervention has been marketed. These studies are designed to monitor effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.

○ NIH-Defined Phase III Clinical Trial. For the purpose of the Guidelines an NIH-defined Phase III clinical trial is a broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or controlled intervention or comparing two or more existing treatments. Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included.

Data and Safety Monitoring Plan. For each clinical trial, NIH requires a data and safety monitoring plan that will provide oversight and monitoring to ensure the safety of participants and the validity and integrity of the data. The level of monitoring should be commensurate with the risks and the size and complexity of the clinical trial. A detailed data and safety monitoring plan must be submitted to the contractor’s IRB and subsequently to the funding IC for approval prior to the accrual of human subjects. The reporting of Adverse Events must be reported to the IRB, the NIH funding Institute or Center, and other required entities. This policy requirement is in addition to any monitoring requirements imposed by 45 CFR part 46.

Data and Safety Monitoring Board (DSMB). NIH requires the establishment of a Data and Safety Monitoring Board (DSMB) for multi-site clinical trials involving interventions that entail potential risk to the participants, and generally for Phase III clinical trials.

Gender. Refers to t the classification of research subjects in either or both of two categories: male and female. In some cases, representation is unknown, because gender composition cannot be accurately determined (e.g. pooled blood samples or stored specimens without gender specification.

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Human Subjects. The HHS regulations “Protection of Human 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

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)).

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

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.)

Manufacturing-related R&D as a result of Executive Order 13329. Encompasses improvements in existing methods or processes, or wholly new processes, machines or systems. Four main areas include:

1. Unit process level technologies that create or improve manufacturing processes including:

○ fundamental improvements in existing manufacturing processes that deliver substantial productivity, quality, or environmental benefits.

○ development of new manufacturing processes, including new materials, coatings, methods, and associated practices.

2. Machine level technologies that create or improve manufacturing equipment, including:

○ improvements in capital equipment that create increased capability (such as accuracy or repeatability), increased capacity (through productivity improvements or cost reduction), or increased environmental efficiency (safety, energy efficiency, environmental impact).

○ new apparatus and equipment for manufacturing, including additive and subtractive manufacturing, deformation and molding, assembly and test, semiconductor fabrication, and nanotechnology.

3. Systems level technologies for innovation in the manufacturing enterprise, including:

○ advances in controls, sensors, networks, and other information technologies that improve the quality and productivity of manufacturing cells, lines, systems, and facilities.

○ innovation in extended enterprise functions critical to manufacturing, such as quality systems, resource management, supply change integration, and distribution, scheduling and tracking.

4. Environment or societal level technologies that improve workforce abilities, productivity, and manufacturing competitiveness, including:

○ technologies for improved workforce health and safety, such as human factors and ergonomics.

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

○ technologies that aid and improve workforce manufacturing skill and technical excellence, such as educational systems incorporating improved manufacturing knowledge and instructional methods.

○ technologies that enable integrated and collaborative product and process development, including computer-aided and expert systems for design, tolerancing, process and materials selection, life-cycle cost estimation, rapid prototyping, and tooling.

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:

a. 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

b. 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).

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:

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

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

3. A systematic application of knowledge toward the production of useful materials, devices, and systems or methods, including design, development, and improvement of prototypes…