Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Human Genome Research Institute (NHGRI)
Funding Opportunity Title	Revolutionary Genome Sequencing Technologies The $1000 Genome (SBIR [R43/R44])
Activity Code	R43/R44 Small Business Innovation Research (SBIR) Grant - Phase I, Phase II, and Fast-Track
Announcement Type	Reissue of RFA-HG-10-014
Related Notices	October 18, 2013 - See Notice NOT-OD-14-003. Guidance on Resumption of NIH Extramural Activities Following the Recent Lapse in Appropriations. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.
Funding Opportunity Announcement (FOA) Number	RFA-HG-13-007
Companion Funding Opportunity	RFA-HG-13-005, R01 Research Project Grant RFA-HG-13-006, R21 Exploratory/Developmental Research Grant Award
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.172
Funding Opportunity Purpose	The National Human Genome Research Institute (NHGRI) solicits SBIR (R43/R44) grant applications to develop novel technologies that will enable extremely low-cost, high quality DNA sequencing. The goal of this initiative is to reduce the cost of sequencing a mammalian-sized genome to approximately $1000. Applicants may propose to develop full-scale sequencing systems or to investigate challenges underlying key system components. Exploration of methods other than those currently being pursued as potential $1,000 genome technologies is encouraged. High-risk/high-payoff applications are appropriate to achieve the goals of this FOA.

Posted Date	June 26, 2013
Open Date (Earliest Submission Date)	September 17, 2013
Letter of Intent Due Date(s)	September 1, 2013
Application Due Date(s)	(Extended to November 1, 2013 per NOT-OD-14-003) October 17, 2013, by 5:00 PM local time of applicant organization
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	February-March 2014
Advisory Council Review	May 2014
Earliest Start Date	July 2014
Expiration Date	(Extended to November 2, 2013 per NOT-OD-14-003) October 18, 2013
Due Dates for E.O. 12372	Not Applicable

It is critical that applicants follow the instructions in the SF424 (R&R) SBIR/STTR Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Purpose

The National Human Genome Research Institute (NHGRI) solicits R43/R44 grant applications to develop novel technologies that will enable extremely low-cost, high quality DNA sequencing. This FOA continues a program that began in 2004, when the cost to produce a high quality draft mammalian genome sequence was estimated at $5 to $10 million, and the goal was to reduce costs by four orders of magnitude to approximately $1,000 in ten years.

While substantial progress toward the $1,000 genome has been made, daunting scientific and technical challenges remain. This program will continue to support both fundamental scientific investigation underlying the technologies, and their engineering, to achieve this goal. The program supports development of key system components and of full systems. In this context, key components refers to the method for determining the linear order of nucleotides, in contrast to upstream or downstream steps in sequencing. Exploration of methods other than those currently being pursued as potential $1,000 genome technologies is encouraged. High-risk/high-payoff applications are appropriate to achieve the goals of this FOA.

Background

The ability to sequence complete genomes and the free dissemination of sequence data have dramatically changed the nature of biological and biomedical research. Sequence and other genomic data have the potential to lead to remarkable improvement in many facets of human life and society, including the understanding, diagnosis, treatment and prevention of disease; advances in agriculture, environmental science and remediation; and our understanding of evolution and ecological systems.

The ability to sequence many genomes completely has been made possible by the enormous reduction of the cost of sequencing in the past 30 years, from tens of dollars per base in the 1980s to a fraction of a cent per base today. We have progressed from the early Human Genome Project goals to sequence the genomes of the human and mouse and a few additional model organisms (E. coli, C. elegans and D. melanogaster), through programs to sequence at varying pre-determined quality levels numerous genomes across the evolutionary tree including multiple species and variants for some of those, to current programs to sequence portions or the entire genomes of increasing numbers of tumors and human individuals. Technology advances, and in particular the recent emergence of a new generation of sequencing systems, have enabled the launch of several such projects that are producing stunning insights into biology and disease. Nevertheless, the cost to completely sequence large numbers of entire genomes remains too high to allow complete genome sequencing to be used routinely, and we remain far from achieving the low costs and high quality needed to enable the use of comprehensive genomic sequence information in individual health care.

A few examples of high priority research to which genomic sequencing at high quality and dramatically reduced cost would make vital contributions include:

• Comparative genomic analyses across species to yield insights into the structure and function of the human genome and, consequently, the genetics of human health and disease;
• Studies of human genetic variation and its relationship to health and disease, in large numbers of individuals, that capture not only common single nucleotide variation but also rare, copy number, and structural variants that are increasingly thought to play an important role in complex disease;
• Characterization of somatic changes in the genome that contribute to cancer, revealing information from large numbers of matched tumor/normal samples on a genome-wide basis rather than restricting analysis to suspect genomic regions that are based on incomplete knowledge;
• Additional genome sequences of agriculturally important animals and plants that are needed to study individual variation, different domesticated breeds and wild variants of each species; and
• Sequence analysis of microbial communities, many members of which cannot be cultured. This will provide a rich source of medically and environmentally useful information. Accurate, rapid sequencing may also be the best approach to microbial monitoring of food and the environment, including rapid detection and mitigation of bioterrorism threats.

The broad utility and high importance of dramatically reducing DNA sequencing costs prompted the NHGRI, in 2004, to embark on two parallel technology development programs (Nature Biotech. 26:1113, 2008). The first had the objective of reducing the cost of producing a high quality sequence of a mammalian-sized genome by two orders of magnitude, to about $100,000. This goal has been achieved so no additional grant applications are being solicited at this time. Rather, the NHGRI is focusing its efforts on attaining the goal of the second program, which, as described in this FOA and parallel FOAs for other grant mechanisms, is the development of technologies with which to sequence a human genome for about $1,000 (a four order of magnitude cost reduction). Implicit in this goal is the quality of the expected sequence product, as sequencing cost targets are meaningless without associated quality standards as described below.

Sequencing Strategy and Quality

The sequencing technology that was used to produce the reference human genome sequence (Nature 431:931, 2004; Nature 409:860, 2001; Science 291:1304, 2001) was fluorescence detection of dideoxynucleotide-terminated DNA extension reactions resolved by capillary array electrophoresis (CAE). Individual sequence read segments can be as long as 1000 nucleotides. If all of the DNA in a 3 Gb genome were unique, it would be possible to determine the sequence of the entire genome by generating a sufficient number (tens of millions) of randomly-overlapping 1000-base reads and aligning their overlaps. However, the human and the majority of other interesting genomes contain a substantial amount of repetitive DNA. To cope with the complexities of repetitive DNA elements and to assemble the thousand-base reads in the correct long-range order across the genome, genomic sequencing methods involve a variety of additional strategies, such as the sequencing of both ends of cloned DNA fragments, use of libraries of cloned fragments of specified lengths, incorporation of map information, achievement of substantial redundancy (multiple reads of each nucleotide from overlapping fragments) and application of sophisticated assembly algorithms to filter and align the reads. As new sequencing technologies are developed, they must incorporate means to deal with these features of the structure of the genome.

The gold standard for genomic sequencing is based on the above-described methods and remains =99.99% accuracy (not more than one error per 10,000 nucleotides) with essentially no gaps (http://www.genome.gov/10000923). The finishing steps needed to achieve that very high quality have not been automated and thus require substantial hand-crafting. However, experience shows that much comparative and medically useful sequence information can be obtained from automatically generated sequence assemblies that are known as high-quality draft or comparative grade. Therefore, the cost targets for NHGRI’s sequencing technology development programs were originally defined in terms of a mammalian-sized genome with a sequence quality equivalent to or better than that of the mouse draft assembly published in December 2002 (Nature 420:520, 2002). Producing such a product for $1,000 is still not possible, so this remains a useful and challenging technology target. Unquestionably, the ultimate need, for medical research and individualized medicine, is for far higher quality sequence of the 3 Gb diploid human genome.

Subsequent to dideoxy/CAE sequencing, a second generation of sequencing technologies has been developed and implemented. These are broadly described as array-based methods in which large numbers of templates are extended one base at a time, the extensions are detected, and that cycle is repeated (reviewed in Nature Biotechnology October 2008). These technologies enable the sequencing of larger numbers of genomes for under $100,000 dollars each, and even less for targeted sequencing of particular genomic regions. While challenges remain related to producing and interpreting sequence information using these technologies, they are proving invaluable to the biomedical research enterprise and they validate the impetus toward further substantial decreases in cost with increases in quality, throughput and speed of genomic sequencing.

The eventual goal of these programs is to achieve technologies that can produce assembled sequence of genomes that had not been previously sequenced (i.e., de novo sequencing). However, an accompanying goal is to obtain highly accurate sequence data at the single base level that can be overlain on a reference sequence of the organism (i.e., re-sequencing). This could be achieved, for example, with short reads that lack information linking them to other reads. In spite of shortcomings (some of which are described below), re-sequencing would potentially be available sooner and of considerable value for certain studies on disease etiology and individualized medicine. Therefore, technology development for re-sequencing will be supported under this FOA. As the cost goal for the more difficult challenge, de novo assembly sequencing, is $1,000, the goal for re-sequencing is to develop technologies that will provide a genome’s worth of less-well-mapped sequence for well below $1,000.

For re-sequencing, the per-base accuracy must be sufficient to distinguish between sequencing errors and real polymorphism. Additional challenges include assigning reads to gene families with very similar sequence, the identification of copy number changes and genomic rearrangements, and the identification of haplotypes (i.e., linear juxtapositioning of particular single nucleotide polymorphism [SNP] alleles along a single chromosome) in diploid organisms. Thus, in proposing the development of re-sequencing technologies, it is essential that the applicant clearly address the extent to which the proposed technology will meet or fall short of these various challenges, and the cost tradeoffs that justify developing the technology to produce data of high value for particular biomedical studies.

The goal of research supported under this FOA is to develop new or improved technology to enable rapid, efficient DNA sequencing of mammalian-sized genomes. The target cost for a 3 Gb diploid genome sequence determined at reasonably high quality is about $1,000 because the ability to generate routinely complete genomic sequences at that cost would revolutionize biological research and medicine.

Both fundamental scientific discovery and cutting edge engineering will likely be needed to achieve these goals. For example, new sensing and detection modalities and fabrication methods may be required, and the physics of systems operating at nm length scales will need to be better understood. It is therefore anticipated that applications responding to this FOA will involve fundamental and engineering research conducted by multidisciplinary teams of investigators. The guidance for budget requests accommodates the formation of groups having investigators at several institutions, in cases where that is needed to assemble a team of the appropriate balance, breadth and experience.

The scientific and technical challenges inherent in achieving the cost goals are significant. Achieving these goals may require research projects that entail substantial risk. That risk should be balanced by an outstanding scientific and management plan designed to achieve the very high payoff goals of this FOA. High-risk/high-payoff projects may fail for legitimate reasons, so applicants proposing such projects should identify them as such, elaborate key quantitative milestones to be achieved, and describe the consequences of not achieving those milestones in a reasonable period of time.

Applicants may propose to develop full-scale sequencing systems or investigate key components of such systems. For the latter, applicants must describe how the knowledge gained as a result of the proposed project would be incorporated into a full system that they or others might subsequently propose to develop. Such independent applications are an important path for pursuing novel, high-risk/high-payoff ideas, short of developing a full system.

While the major focus of this program is on the development of new technologies for detection of nucleotide sequence, any successful technology will have to address matters related to the practical implementation of the technologies so that the technology can form the basis of, or be incorporated into, an efficient, high quality, high-throughput DNA sequencing scheme. Any new technology will eventually need to be incorporated effectively into a sequencing workflow, starting with a biological sample and ending with sequence data of the desired quality. Sample preparation requirements can depend upon the detection method which, in turn, can affect the way in which output data are handled. If a full system development is proposed, these issues should be addressed on an appropriate schedule in the research plan; applicants should focus as early as possible in the research plan on the most critical and highest-risk aspects of the project related to determining the sequence of nucleotides, on which the rest of the project depends. Projects to address key components must address the fundamental method of determining the base sequence (that is, an application addressing only sample prep or only the downstream informatics would not be considered responsive to this FOA).

Most technology developers lack practical experience in high-throughput sequencing and in testing of methods and instruments for robust, routine sequencing operation. Applicants may therefore wish to include such expertise as they develop their teams. Academic investigators may wish to consider collaborating with commercial entities that have the experience and capabilities to bring practical systems into the hands of users.

The quality of sequence to be generated by the technology is of paramount importance for this FOA. Two major factors contributing to genomic sequence quality are per-base accuracy and contiguity of the assembly. Much of the utility of comparative sequence information will derive from characterization of sequence variation between species, and between individuals of a species. Therefore, per-base accuracy must be high enough to discern polymorphism at the single-nucleotide level (substitutions, insertions, deletions) and distinguish polymorphism from sequencing errors. Experience and resulting policy have established a target accuracy of not more than one error per 10,000 bases. All applications in response to this FOA, whether to develop re-sequencing or de novo sequencing technologies, must propose to achieve at least this standard.

Assembly information is needed for determining sequence of new genomes and ultimately also for genomes for which a reference sequence exists, to detect rearrangements, insertions, deletions, and copy number changes. All of these are genomic changes that have been shown to be associated with disease, and knowledge of rearrangements can reveal new biological mechanisms. The phase of single nucleotide polymorphisms to define haplotypes is important in understanding and diagnosing disease. Achieving a high level of sequence contiguity may be essential to achieve the full benefit from the use of sequencing for individualized medicine, e.g., to evaluate genomic contributions to risk for specific diseases and syndromes, and drug responsiveness. Nevertheless, it is recognized that perfect sequence assembly from end to end of each chromosome is unlikely to be achievable with most technologies in a fully automated fashion and without adding considerable cost. Therefore, for the purpose of this FOA, grant applications proposing technology development for de novo sequencing shall describe how they will achieve, for about $1,000, a draft-quality assembly that is at least comparable to that represented by the mouse draft sequence produced by December 2002: 7.7-fold coverage, 6.5-fold coverage in Q20 bases, assembled into 225,000 sequence contigs connected by at least two read-pair links into supercontigs [total of 7,418 supercontigs at least 2 kb long], with N50 length for contigs equal to 24.8 kb and for supercontigs equal to 16.9 Mb (Nature 420:520, 2002). Grant applications that propose technology development for re-sequencing should fully describe the qualities and characteristics of the genomic sequence information that the technology would produce, and the projected cost. That cost should be at least four orders of magnitude lower than was the cost to produce comparable quality data in 2004, when this program was initiated.

Grant applications will be evaluated, and funding decisions made, in such a way as to develop a balanced portfolio that has strong potential to develop both robust de novo and re-sequencing technologies, exploring a variety of technology approaches. If the estimate is correct, that achieving the goal of $1,000 de novo genome sequencing incorporating substantial assembly information will be achieved by about 2014, then low-cost re-sequencing technologies for even lower cost might be expected in a shorter time. Projects with a plan to achieve re-sequencing while on the path to de novo sequencing will receive priority.

Research conducted under this FOA may include development of the computational tools associated with the technology, e.g., to extract sequence information, including image analysis and signal processing, and to evaluate sequence quality and assign confidence scores. It may also address strategies to assemble the sequence from the information being obtained from the technology or by merging the sequence data with information from parallel technology. Applications that incorporate effective plans to develop systems that address the bioinformatics challenges in concert with the sequencing wet-ware will receive high priority consideration. However, this FOA will not support development of sequence assembly or sequence analysis software independent of technology development to obtain the linear nucleotide sequence.

This program is aimed at technology to sequence entire genomes. Projects are under way to determine sequence from selected important regions (e.g., all of the genes). Grant applications that propose to meet the cost targets by sequencing only selected regions of a genome will be considered unresponsive to this FOA. However, applications that propose novel ways to sequence selected genomic regions, cost-effectively, while on a path to whole-genome sequencing, will be considered responsive.

NHGRI is interested in supporting diverse approaches to achieving the goals of this FOA. To assist the research community, investigators who are pursuing one set of technology paths that involve the use of nanopores and nanogaps published an overview of the challenges they face (Nature Biotech. 26:1146, 2008). Similarly, challenges attending sequencing by synthesis have been described (Nature Biotech. 27:1013, 2009). Grant applications to meet these and related challenges, and to pursue alternative technologies, are welcome under this FOA. Information on projects funded under earlier versions of this and related FOAs and a program bibliography are available at http://www.genome.gov/10000368#6.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New (Phase I, Fast-Track) Renewal (Phase II) Resubmission (all phases) Revision The OER Glossary and the SF424 (R&R) SBIR/STTR Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NHGRI intends to commit $2 million FY 2013. The actual number of awards and amount are contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	Budgets up to $250,000 total costs per year for Phase I and up to $1,000,000 total costs per year for Phase II may be requested.
Award Project Period	Durations up to 3 years for Phase I and up to 3 years for Phase II may be requested.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria:

1. Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;

2. Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there must be less than 50 percent participation by foreign business entities in the joint venture;

3. (i) SBIR and STTR. Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these; OR

(ii) SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern; OR

(iii) SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with 121.705(b) concerning registration and proposal requirements.

4. Has, including its affiliates, not more than 500 employees.

If the concern is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these falls under 3 (ii) or 3 (iii) above, see Section IV. Application and Submission Information for additional instructions regarding required application certification.

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

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

Definitions:

• Hedge fund has the meaning given that term in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The hedge fund must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity firm.
• Private equity firm has the meaning given the term private equity fund in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The private equity firm must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.

Venture capital operating company means an entity described in 121.103(b)(5)(i), (v), or (vi). The venture capital operating company must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.

SBCs must also meet the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.

Small business concerns that are more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these are NOT eligible to apply to the STTR program.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, may be allowed.

Applicant organizations must complete the following registrations as described in the SF424 (R&R) SBIR/STTR Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration(formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• SBA Company Registry New requirement. See Section IV. Application and Submission Information, SF424(R&R) Other Project Information Component for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a DUNS number to complete this registration. SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
• Grants.gov
• eRA Commons

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PDs/PIs, at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur.

The SF424 (R&R) SBIR/STTR Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the SF424 (R&R) SBIR/STTR Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and any other HHS funding opportunity, including the SBIR and STTR Parent announcements.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II support, a Phase I awardee should submit a Phase II application within the first six due dates following the expiration of the Phase I budget period.

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

In Phase II, normally, a minimum of one-half or 50% of the research or analytical effort must be carried out by the small business concern. The total amount of consultant and contractual arrangements to third parties for portions of the scientific and technical effort generally may not exceed 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

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

The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of SF424 (R&R) application forms.

Additional details are contained in the SF424 (R &R) SBIR/STTR Application Guide.

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

It is critical that applicants follow the instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Jeffery A. Schloss, Ph.D.
National Human Genome Research
5635 Fisher Lane, Bethesda, MD 20892-9305
For express delivery use 5635 Fishers Lane, Rockville, MD 20850-9305
(submission of letters of intent by email is preferred)
Telephone: 301-496-7531
Email: [email protected]

All page limitations described in the SF424 (R&R) SBIR/STTR Application Guide and the Table of Page Limits must be followed.

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) SBIR/STTR Application Guide to ensure you complete all appropriate optional components.

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

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

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed , with the following additional instructions:

Other Attachments:

1. SBA Company registry

All applicants to the SBIR and STTR programs are required to register at the SBA Company Registry prior to application submission and attach proof of registration. Completed registrations will receive a unique SBC Control ID and .pdf file. If applicants have previously registered, you are still required to attach proof of registration. The SBA Company Registry recommends verification with SAM, but a SAM account is not required to complete the registration. In order to be verified with SAM, your email address must match one of the contacts in SAM. If you are unsure what is listed in SAM for your company, you may verify the information on the SAM site. Confirmation of your company's DUNS is necessary to verify your email address in SAM. Follow these steps listed below to register and attach proof of registration to your application.

a. Navigate to the SBA Company Registry.

b. If you are a previous SBIR/STTR awardee from any agency, search for your small business by Company Name, EIN/Tax ID, DUNS, or Existing SBIR/STTR Contract/Grant Number in the search fields provided. Identify your company and click Proceed to Registration .

c. If you are a first time applicant, click the New to the SBIR Program? link on lower right of registry screen.

d. Fill out the required information on the Basic Information and Eligibility Statement screens.

e. Press Complete Registration on the lower right of the Eligibility Statement screen and follow all instructions.

f. Download and save your SBA registry PDF locally. The name will be in the format of SBC_123456789.pdf, where SBC_123456789 (9 digit number) is your firm’s SBC Control ID. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

g. When you are completing the application package, attach this SBA registry PDF as a separate file by clicking Add Attachments located to the right of Other Attachments on the Research and Related Other Project Information form.

For questions and for technical assistance concerning the SBA Company Registry, please contact the SBA at http://sbir.gov/feedback?type=reg.

2. SBIR Application Certification for small business concerns majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms

Applicant small business concerns that are majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms (e.g. majority VCOC-owned) are required to submit a Certification at time of their application submission per the SBIR Policy Directive. Follow the instructions below.

Applicants small business concerns who are more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these (i.e. NOT majority VCOC-owned) should NOT fill out this certification and should NOT attach it their application package.

a. Download the SBIR Application VCOC Certification.pdf at the NIH SBIR Forms webpage.

b. Answer the 3 questions and check the certification boxes.

c. The authorized business official must sign the certification.

d. Save the certification using the original file name. The file must be named SBIR Application VCOC Certification.pdf . DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

e. When you are completing the application package, attach this certification as a separate file by clicking Add Attachments located to the right of Other Attachments on the Research and Related Other Project Information form.

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

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed, with the following additional instructions:

Applicants should request travel funds for the PD/PI and two additional lead investigators to attend the annual grantee meetings (see information about these meetings under the heading, Resource Sharing Plan).

Applicants may include funds for an internally appointed advisory board. However, potential advisors should not be contacted prior to submitting the application, nor should potential advisors be named in the grant application, to avoid conflicts of interest in the review process.

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

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

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed, with the following additional instructions:

Research Strategy: A detailed research strategy should include a description of the level of risk of key technical challenges, alternative approaches, go/no-go decision points, etc. It should also include a detailed timeline accompanied by quantitative milestones (see below) that address the key scientific and technical challenges central to the approach. The timeline and milestones are essential for use by the grantee and the NHGRI for planning the research project and assessment of progress toward goals, and by the reviewers for evaluating the application.

Timelines and quantitative milestones are essential for development of a realistic research strategy; they provide a basis for project leaders to make decisions, assess their own progress, set priorities, and redistribute resources when needed. It will be particularly important to establish quantitative milestones in cases where subsequent steps in technology development depend upon threshold performance characteristics of earlier developments. Elaboration of timelines and milestones is primarily the responsibility of the applicant, and the quality and utility of the proposed timelines and milestones will be a review criterion, because they reflect the insights and judgment of the applicant concerning key challenges and how best to conduct the research. The NHGRI appreciates that these projects will require research, not just engineering; progress toward milestones will be evaluated accordingly. If the proposed timeline and milestones are not adequate in the case of an otherwise meritorious application, reviewers of the application may make recommendations to NHGRI regarding improved timelines and milestones.

The applicant's plans to manage risk by managing key project decision points, determining resource re-allocation, project re-direction, etc., should be clearly described as an element of the Research Strategy. If an internal advisory board is planned, its role in managing project decision points and resource allocation should also be described.

Projects that propose to build sequencing systems (in contrast to developing components) that will be assembled by the end of the project period may wish to present a strong case for that system’s capabilities by proposing to demonstrate the sequencing of a substantial amount of DNA (e.g., mega- to gigabases) at the target cost and quality; other measures may be proposed by the applicant.

Resource Sharing Plans

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) SBIR/STTR Application Guide.

To accelerate progress in the field of advanced DNA sequencing technology development, grantees will be required to participate actively and openly in at least one grantee meeting per year. Substantial information sharing will be required and is a condition of the award; failure to openly share information may be grounds for discontinuation of funding if the goals of the program cannot be met. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the technology. Applicants should describe their plans for participating in the grantee meetings and for managing the intellectual property concerns in the context of those meetings and other opportunities for information sharing. Other investigators in the field (i.e., not supported under this program) may be invited to participate in these workshops; their agreement to share information substantially will be a prerequisite to participation.

Applicants are expected to describe their plan for providing access to the technology developed under this grant support, and information about that technology, consistent with achieving the goals of this program. For example, the technology might be made available as a fee-for-service, through sale of instruments and/or reagents, through collaboration, through publication and posting of results, plans and methods, or by other means. If any quantity of sequence data will be collected under grant support, it is expected that a plan to disseminate those data will be described, consistent with achieving the goals of this program.

Appendix

Do not use the Appendix to circumvent page limits. The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide, with the following additional instruction:

Note that Phase I SBIR/STTR Appendix materials are not permitted.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) SBIR/STTR Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) SBIR/STTR Application Instructions. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) SBIR/STTR Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NHGRINIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115, with the following modifications: Applicants may submit late-breaking research findings (maximum of 1 printed page) thirty days before the review.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed project have commercial potential to lead to a marketable product, process or service? (In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization?)

Does the research plan propose to enable extremely low-cost, rapid, high-quality DNA sequencing?

Are the plans sufficiently bold to constitute a substantial advance, if they can be achieved, toward extremely low-cost, rapid, high-quality DNA sequencing?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Are key scientific and technological challenges on which the rest of the approach depends, identified and addressed early in the project?

Does the proposed technology address sequence quality and the sequencing of entire genomes?

Does the application clearly state whether the goal is to develop re-sequencing, or de novo sequencing technology, and if the latter, is there an adequate plan for evaluating the achieved long-range contiguity?

Is the analysis of sequencing costs well developed and well-informed, relative to the state of the technology?

Are bold plans counterbalanced to manage the inherent risk, for example by firm theoretical basis, reasonable preliminary data (depending on the mechanism), the track record of the lead investigators, and an outstanding scientific and management plan?

Are the timeline and milestones logical and realistic?

Are key technical barriers and dependencies identified?

Are milestones adequately developed and quantitative, to serve as effective guidance for assessment of progress by the investigators and the NHGRI?

Are plans to participate actively and openly in grantee meetings sufficiently clear and forthcoming so as to contribute substantially to advancement of the field?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangement?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Phase II Applications

For Phase II Applications, how well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

Phase I/Phase II Fast-Track Applications

For Phase I/Phase II Fast-Track Applications, reviewers will consider the following:

1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

2. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Phase IIB Competing Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHGRI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a committee process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with resource sharing plans

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

The Office of Inspector General Hotline accepts tips from all sources about potential fraud, waste, abuse and mismanagement in Department of Health & Human Services programs. The reporting individual should indicate that the fraud, waste and/or abuse concerns an SBIR/STTR grant or contract, if relevant. Report Fraud.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

NIH requires that SBIR/STTR grantees submit the following reports within 90 days of the end of the grant budget period unless the grantee is under an extension.

• Final Progress Report (requirements have recently changed - please see the NOT-OD-12-152)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR) replaced the Final Cash Transaction Report (PSC 272)
• Phase II Data Collection Requirement for Government Tech-Net Database

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI.

For details about each specific required report, see the section on Award Guidelines, Reporting Requirements, and Other Considerations, in the SF424 (R&R) SBIR/STTR Application Guide.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

SBA Company Registry (Questions regarding required registration at the SBA Company Registry and for technical questions or issues)

Website to Email: http://sbir.gov/feedback?type=reg.

Jeffery A. Schloss, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531
Email: [email protected]

Ken Nakamura, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-0838
Email: [email protected]

Cheryl Chick
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, and P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011). The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.