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Extramural Research

Funding Opportunities

U.S. Environmental Protection Agency
Office of Research and Development
National Center for Environmental Research
Science to Achieve Results (STAR) Program

CLOSED - FOR REFERENCES PURPOSES ONLY

Organotypic Culture Models for Predictive Toxicology Center

Special Announcements

This is the initial announcement of this funding opportunity.

Funding Opportunity Number: EPA-G2013-STAR-L1

Catalog of Federal Domestic Assistance (CFDA) Number: 66.509

Solicitation Opening Date: September 23, 2013
Solicitation Closing Date: January 23, 2014, 11:59:59 pm Eastern Time

Eligibility Contact: Ron Josephson (josephson.ron@epa.gov); phone: 703-308-0442
Electronic Submissions: Todd Peterson (peterson.todd@epa.gov); phone: 703-308-7224
Technical Contact: Barbara Klieforth (klieforth.barbara@epa.gov); phone: 703-347-8044

Table of Contents:
SUMMARY OF PROGRAM REQUIREMENTS
Synopsis of Program
Award Information
Eligibility Information
Application Materials
Agency Contacts
I. FUNDING OPPORTUNITY DESCRIPTION
A. Introduction
B. Background
C. Authority and Regulations
D. Specific Areas of Interest/Expected Outputs and Outcomes
E. References
F. Special Requirements
II. AWARD INFORMATION
III. ELIGIBILITY INFORMATION
A. Eligible Applicants
B. Cost Sharing
C. Other
IV. APPLICATION AND SUBMISSION INFORMATION
A. Internet Address to Request Application Package
B. Content and Form of Application Submission
C. Submission Dates and Times
D. Funding Restrictions
E. Submission Instructions and Other Submission Requirements
V. APPLICATION REVIEW INFORMATION
A. Peer Review
B. Programmatic Review
C. Human Subjects Research Statement (HSRS) Review
D. Funding Decisions
VI. AWARD ADMINISTRATION INFORMATION
A. Award Notices
B. Disputes
C. Administrative and National Policy Requirements
VII. AGENCY CONTACTS

Access Standard STAR Forms (Forms and Standard Instructions Download Page)
View research awarded under previous solicitations (Funding Opportunities: Archive Page)

SUMMARY OF PROGRAM REQUIREMENTS

Synopsis of Program:
The U.S. Environmental Protection Agency (EPA), as part of its Science to Achieve Results (STAR) program, is seeking applications for research centers to investigate toxic effects of chemical substances in three-dimensional (3D) in vitro models, hereafter referred to as ‘organotypic culture models’ (OCMs). OCMs are tissue culture models that mimic in vivo tissue architecture through interactions of heterotypic cell types (e.g., epithelium-stroma) and extracellular matrices (ECM). They can be established from isolated cells or from tissue fragments harvested in vivo, and will bridge the gap between conventional monolayer cell cultures and whole-animal systems.

EPA is interested in the potential application of OCMs that mimic complex cell arrangements and physiologies, scalable from mid to higher throughput screening (HTS), and high-content screening (HCS) approaches. This solicitation seeks the formation of research centers that will guide the development and evaluation of OCMs that will accelerate translational research in predictive toxicology. Three dimensional tissue models may, for example, utilize animal cells combined with mechanical scaffolds or microfluidics devices. Under this solicitation, the successful applicant will lead a Center to craft OCMs that can recapitulate critical features of in vivo cellular organization and communication, cell-matrix interplay, morphogenetic processes and differentiation, physiology and chemical metabolism. Measures of success or progress should be described toward the application of OCMs for computational toxicology and reconstructing in vivo responses to environmental chemicals and nanomaterials to improve environmental health protection. As such, the OCMs should be scalable in support of medium to high throughput strategies or high-dimensional quantitative data collection, such as high content imaging, that respond to questions relevant to chemical risk assessment and management.  For applications using human cells, it is preferred that the cells are already available or derive from available cell lines. Under EPA Regulation 40 CFR Part 26 (Protection of Human Subjects), using pre-existing human cell lines is not considered human subjects research. 

This solicitation provides the opportunity for the submission of applications for projects that may involve human subjects research.  Human subjects research supported by the EPA is governed by EPA Regulation 40 CFR Part 26 (Protection of Human Subjects).  This includes the Common Rule at subpart A and prohibitions and additional protections for pregnant women and fetuses, nursing women, and children at subparts B, C, and D.  Research meeting the regulatory definition of intentional exposure research found in subpart B is prohibited by that subpart in pregnant women, nursing women, and children.  Research meeting the regulatory definition of observational research found in subparts C and D is subject to the additional protections found in those subparts for pregnant women and fetuses (subpart C) and children (subpart D).  All applications must include a Human Subjects Research Statement (HSRS, as described in Section IV.B.8), and if the project involves human subjects research, it will be subject to an additional level of review prior to funding decisions being made as described in Sections V.C and V.D of this solicitation.

Guidance and training for investigators conducting EPA-funded research involving human subjects may be obtained here:
Ethics, Regulations, and Policies
Human Subjects Research at the Environmental Protection Agency: Ethical Standards and Regulatory Requirements

Award Information:
Anticipated Type of Award: Grant  
Estimated Number of Awards: Approximately 3 awards
Anticipated Funding Amount: Approximately $18 million total for all awards
Potential Funding per Award: Up to a total of $6 million, including direct and indirect costs, with a maximum duration of 4 years.  Cost-sharing is not required.  Proposals with budgets exceeding the total award limits will not be considered.

Eligibility Information:
Public nonprofit institutions/organizations (includes public institutions of higher education and hospitals) and private nonprofit institutions/organizations (includes private institutions of higher education and hospitals) located in the U.S., state and local governments, Federally Recognized Indian Tribal Governments, and U.S. territories or possessions are eligible to apply. See full announcement for more details.

Application Materials:
To apply under this solicitation, use the application package available at Grants.gov (for further submission information see Section IV.E. “Submission Instructions and other Submission Requirements”).  The necessary forms for submitting a STAR application will be found on the National Center for Environmental Research (NCER) web site, Forms and Standard Instructions Download Page.

If your organization is not currently registered with Grants.gov, you need to allow approximately one month to complete the registration process. Please note that the registration process also requires that your organization have a DUNS number and a current registration with the System for Award Management (SAM) and the process of obtaining both could take a month or more.  Applicants must ensure that all registration requirements are met in order to apply for this opportunity through grants.gov and should ensure that all such requirements have been met well in advance of the submission deadline.  This registration, and electronic submission of your application, must be performed by an authorized representative of your organization.

If you do not have the technical capability to utilize the Grants.gov application submission process for this solicitation, send a webmail message at least 15 calendar days before the submission deadline to assure timely receipt of alternate submission instructions.  In your message  provide the funding opportunity number and title of the program, specify that you are requesting alternate submission instructions, and provide a telephone number, fax number, and an email address, if available.  Alternate instructions will be emailed whenever possible.  Any applications submitted through alternate submission methods must comply with all the provisions of this Request for Applications (RFA), including Section IV, and be received by the solicitation closing date identified above.

Agency Contacts:
Eligibility Contact: Ron Josephson (josephson.ron@epa.gov); phone: 703-308-0442
Electronic Submissions: Todd Peterson (peterson.todd@epa.gov); phone: 703-308-7224
Technical Contact: Barbara Klieforth (klieforth.barbara@epa.gov); phone: 703-347-8044

I. FUNDING OPPORTUNITY DESCRIPTION

A. Introduction
Understanding the potential health risks posed by chemical substances in the environment is a  major challenge elevated by the large number of diverse chemical substances with generally uncharacterized exposures, mechanisms, and toxicities. Tens of thousands of chemicals are currently in use and hundreds more are introduced every year. Many of these chemical substances, including nanomaterials, have not been thoroughly evaluated for potential risks to human health and the environment. A national research priority in the EPA’s Office of Research and Development (ORD) is Chemical Safety for Sustainability (CSS). Moving toward a safer and more sustainable environment requires new information and methods to make better-informed, more-timely decisions about chemicals. This requires innovative toxicity testing methods and new prediction techniques in computational toxicology that integrate multiple fields of science and technology to better understand the basis of lifestage-specific susceptibilities. EPA currently supports a number of computational toxicology-related research grants resulting from previous solicitations. Information regarding current research can be found on ORD’s National Center for Environmental Research (NCER) web site at Computational Toxicology.

EPA’s CSS Research Program is investigating new ways to address several longstanding difficulties with managing the safety of chemical substances, particularly in assessing their potential risk to human health and the environment. For example, there are over 80,000 chemicals in the Toxic Substance Control Act (TSCA) Inventory, yet only a small number have extensive toxicity testing information. Traditional chemical toxicity testing is expensive, time consuming and uses a significant number of animals. Although not perfect, the current model systems for predicting toxicity, classifying environmental hazards, and evaluating dose-response have been the gold standard for many years. A new testing paradigm was recommended by the National Research Council for the 21st Century in which the traditional methods would be enhanced or replaced with cell-based in vitro approaches that inform targeted-testing with in vivo models. A research goal of EPA is to support the development of tools to rapidly screen and evaluate large numbers of chemicals in manners that become less reliant on whole animal tests and will rely instead on systems-oriented, computational models. These data and models would help elucidate pathways that proceed from an initiating molecular event in which a chemical interacts with a biological target(s); continue on through a sequential series of key events embedded in biological processes; and ultimately culminate in an adverse outcome to humans or ecological species.

This solicitation is seeking applications proposing to lead investigations on three-dimensional in vitro models, hereafter referred to as ‘organotypic culture models’ (OCMs), that can discern toxic effects of chemical substances.  Tissues and organs are three dimensional (3D) and function in a 3D milieu.  Toxicological studies have been relying primarily on two-dimensional (2D) cell culture and animal model systems. However, cells grown on rigid 2D substrata can differ from in vivo systems in most aspects of cellular function, including morphology, proliferation, differentiation and communication within and between cells. OCMs have the advantage of being amenable to rapid experimental manipulations and imaging techniques, often difficult or impractical using whole-animal systems. OCMs using living cells that mimic structural and physiological features of animal tissues thus bridge the gap between conventional monolayer cell cultures and in vivo models. The development and evaluation of foreseen OCMs should accelerate translational research in computational toxicology. For applications using human cells, it is preferred that the cells are already available or derive from available cell lines. Under EPA Regulation 40 CFR Part 26 (Protection of Human Subjects), using pre-existing human cell lines is not considered human subjects research. 

This solicitation provides the opportunity for the submission of applications for projects that may involve human subjects research.  Human subjects research supported by the EPA is governed by EPA Regulation 40 CFR Part 26 (Protection of Human Subjects).  This includes the Common Rule at subpart A and prohibitions and additional protections for pregnant women and fetuses, nursing women, and children at subparts B, C, and D.  Research meeting the regulatory definition of intentional exposure research found in subpart B is prohibited by that subpart in pregnant women, nursing women, and children.  Research meeting the regulatory definition of observational research found in subparts C and D is subject to the additional protections found in those subparts for pregnant women and fetuses (subpart C) and children (subpart D).  All applications must include a Human Subjects Research Statement (HSRS, as described in Section IV.B.8), and if the project involves human subjects research, it will be subject to an additional level of review prior to funding decisions being made as described in Sections V.C and V.D of this solicitation.

Guidance and training for investigators conducting EPA-funded research involving human subjects may be obtained here:
Ethics, Regulations, and Policies
Human Subjects Research at the Environmental Protection Agency: Ethical Standards and Regulatory Requirements

B. Background
Technological and scientific advances in cell and molecular biology, chemistry and toxicology, computer science and systems modeling are leading to new ways to more effectively and efficiently rank chemicals based on their in vitro biological activity and potential exposure. The objective of the research Center(s) to be supported under this RFA is to further the development and evaluation of OCMs that will help accelerate translational research in predictive toxicology. It is expected that these OCMs will provide data at a higher level of biological organization not currently captured with cell-molecular based assays. OCMs that capture the complex 3D physiology of an in vivo tissue or organ are expected to provide tools, models, and data on critical linkages between molecular targets and tissue-level alterations. Research Centers responsive to this solicitation will develop and/or evaluate OCMs that: (1) recapitulate in vitro the sequential steps leading to AOPs for in vivo endpoints relevant to environmental health protection (e.g., development, reproduction, cancer); (2) are amenable to higher throughput formats because of the need to test a large number of chemicals and their break-down products that may be environmental contaminants; and (3) are amenable to quantitative multiplexed and multi-resolution assays (e.g., high content imaging, genomic approaches) in routine assay formats. Specific areas of interest include OCMs that can be used to test for the effects of chemicals on biological pathways and cellular dynamics relevant to development, reproduction, endocrine disruption, and cancer, and that could provide quantitative information to predict dose-response. Examples of specific areas of interest include, but are not limited to, cell-cell signaling pathways (e.g., Wnt, Shh, Delta-Notch, TGF-beta, Receptor Tyrosine Kinases, and retinoic acid receptors) and endocrine pathways (e.g., estrogen, thyroid, adrenal, and hypothalamic-pituitary) and their associated target tissues.  Emphasis should be placed on assays with the capability to be run in a reproducible, medium or high-throughput manner.

OCMs may make use of tissues harvested in vivo (e.g., embryonic tissue) to follow morphogenesis and differentiation, e.g., brain-slices to follow synaptic development in a particular region of the nervous system (e.g., hippocampus), or stabilizing metabolic competency in liver. For longer-term evaluation, 3D models may be established starting from cells isolated from tissues, cell lines or stem cells. Reciprocal stromal-epithelial interactions are key events in AOPs for breast cancer that can be missed in a 2D culture system platform. Due to subtleties in cell shape and polarity, growth and malignant behavior of mammary epithelial cells can be regulated at the level of the tissue organization.  Most cells have polarity and a directional function associated with that polarity. As such, OCMs likely need to maintain or include cellular polarity in order to approach normal function (e.g., apical and baso-lateral compartments). In some instances such polarity can be mechanical and in others can be the result of self-assembly or differentiation in culture where tight junctions form and tissue-like features emerge, cultivation of pluripotent stem cells on 3D scaffolds allows the generation of organ-like structures that resemble their in vivo counterparts when supported by appropriate micro-environmental cues.

Relatively little is known concerning the potential toxicological risks of the great majority of chemicals in commerce or in the environment because they have not been tested adequately.  Testing of the safety of chemicals has relied heavily on contentious, resource-intensive in vivo testing. A challenge for human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. Diverse in vitro screening assays are now being applied for testing of large numbers of chemical substances for biological activity and potential toxicity. Many significant findings in cell biology and toxicology have come from cultures of cells grown in monolayer; however, in vivo tissues and organ systems develop in 3 dimensions. Cells grown on flat, rigid 2D substrata can differ in their morphology, differentiation, and cell signaling versus those growing in a more physiological 3D environment. It has been shown that cells in 2D often have different patterns of gene expression as compared to those in 3D systems.

Several factors have motivated the development and evaluation of ‘Organotypic Culture Models’ (OCMs) for modeling cellular systems. One is the need for research models that capture complex cell-cell and cell-extracellular matrix (ECM) interactions and stabilize cell growth, organization and differentiation. In tissues, cells connect not only to each other but also to the ECM. This imparts distinct mechanical properties but also contributes to biochemical cues to the cellular environment via selective binding and release of growth factors, cytokines, morphogens, and other biologically active molecules. Receptors on the cell surface may determine how the cells interpret these cues. For example, ECM-mediated signal transduction events can lead to diverse changes in gene expression that influence the spatio-temporal fate of cells. Biochemical signals or responses that go awry due to genetic errors or chemical disruption in the system may have deleterious consequences on higher order tissue structure or function. These adverse outcome pathways (AOP) may lead to cancers, developmental defects, or disruptions in normal function. The adverse outcome pathway is a conceptual framework to portray causal and predictive linkages between molecular-cellular disruption (initiation of a toxicity or disease pathway) and adverse outcomes relevant to risk assessment and management. Subtleties in the complex mechanical and biochemical interplay underlying the coordinated regulation of these cellular activities are not easily captured in a conventional 2D assay format. Many studies have shown little correlation between the relative toxicity of nanoparticles following in vitro cellular and in vivo exposures[e.g., Sayes et. al. 2007]. Even co-cultures of alveolar epithelial cells and macrophages have not completely simulated the lung microenvironment with regard to surfactant interaction, particle clearance and recruitment of inflammatory cells in the lungs [Sayes et al, 2007].

Therefore, there is a growing demand for innovative 3D tissue mimetics that capture more of the relevant biology of the cellular micro-environment than traditional 2D cultures can possibly deliver. While 2D models can reveal important influences of the micro-environment on individual cellular behaviors (e.g., shape, cytoskeletal arrangement, chemotaxis and cell migration, differential growth and adhesion), it is the hierarchical arrangements and collective behavior of many interacting cells in a complex 3D architecture that drives the response of an integrated system. As such, OCMs may help to advance scientific understanding of the underlying pathophysiology and multicellular consequences that link molecular initiating events to key cell events in AOPs relevant to chemical risks.

Another motivation for the development of OCMs is the need for routine mid- to high-throughput assay formats that capture important facets of a physiological response to chemicals or their metabolites. While animal models may capture much of this complexity, they do not always predict toxicological effects in humans, nor facilitate an increased understanding of the mechanistic pathways and modes of action. OCMs based on human cells may capture the subtleties of a complex 3D tissue physiology to help identify molecular initiating events and establish mechanisms in screening of chemical substances for biological activity. As such, modeling cellular systems using in vitro 3D systems can help narrow the gap between animal models and human studies for toxicological effects of chemical substances.

A third motivation is the need to develop improved simulations of complex biological systems. To support chemical risk assessment paradigms that rely heavily on high throughput in vitro chemical screening data, in silico models of complex biological systems are needed to translate in vitro effects data into predicted in vivo outcomes, including relevant concentration-duration-response relationships. OCMs represent critical research tools that can be manipulated experimentally in a manner that allows paracrine regulation among closely associated cells and/or cell types to be differentiated from autocrine regulation within cells and endocrine regulation between tissues and organ systems within a whole organism. As such, they are positioned to provide unique insights into biological control mechanisms that can lead to more complex biological simulations that consider interactions of cells and cell types within a 3D milieu.

General Description of EPA Extramural Research Center

A Research Center, as intended in this RFA, entails multidisciplinary, thematic approaches to research needs on a much broader scale than individual projects. A Center allows for flexibility in examining not just the most recent science, but the full complement of considerations that may impact an issue, e.g., social or technical, as they develop. In promoting integrated, trans-disciplinary research, EPA seeks applications that demonstrate that the research team has worked together to design the proposed program, ensure that the Center reflects the input and interactions of different disciplines within the team, and that the Center as a whole reflects the collective thinking of a multidisciplinary team. It is not sufficient to list a collection of insular projects even if they address complementary topics. EPA recognizes that tight scientific integration can be a challenge, but this is a high priority for the Agency. Applicants are expected to: demonstrate how the various activities and projects contained within their proposals are integrated; encourage participation of investigators with the needed expertise and qualifications; employ cutting-edge technologies and approaches; and engage eligible stakeholders and partners who can help the Center achieve the goals of this RFA. This RFA presents the opportunity for investigators from different disciplines and organizations to work together on larger problems than can be addressed in a single grant proposal. Applicants are expected to propose projects (a maximum of five) within the Center that collectively adequately address the research needs described in this RFA.

In order to stimulate state-of-the-art research results, partnerships and collaborations are strongly encouraged and will be evaluated as part of the peer review evaluation under Section V.  Please refer to Contracts and Subawards if your organization intends to identify a collaborator, including an independent third party evaluator in your proposal, and intend to use EPA funds to compensate them.   

The specific Strategic Goal and Objective from the EPA’s Strategic Plan that relate to this solicitation are:

Goal 4: Ensuring the Safety of Chemicals and Preventing Pollution, Objective 4.1: Ensure Chemical Safety,

More information can be found in EPA’s FY 2011-2015 Strategic Plan

C. Authority and Regulations
The authority for this RFA and resulting awards is contained in the Toxic Substances Control Act, Section 10, 15 U.S.C. 2609, and the Federal Insecticide, Fungicide, and Rodenticide Act, Section 20, 7 U.S.C. 136r.

For research with an international aspect, the above statutes are supplemented, as appropriate, by the National Environmental Policy Act, Section 102(2)(F).

Note that a project’s focus is to consist of activities within the statutory terms of EPA’s financial assistance authorities; specifically, the statute(s) listed above.  Generally, a project must address the causes, effects, extent, prevention, reduction, and elimination of air pollution, water pollution, solid/hazardous waste pollution, toxic substances control, or pesticide control depending on which statute(s) is listed above.  These activities should relate to the gathering or transferring of information or advancing the state of knowledge.  Proposals should emphasize this “learning” concept, as opposed to “fixing” an environmental problem via a well-established method.  Proposals relating to other topics which are sometimes included within the term “environment” such as recreation, conservation, restoration, protection of wildlife habitats, etc., must describe the relationship of these topics to the statutorily required purpose of pollution prevention and/or control.

Applicable regulations include: 40 CFR Part 30 (Uniform Administrative Requirements for Grants and Agreements with Institutions of Higher Education, Hospitals, and Other Non-Profit Organizations), 40 CFR Part 31 (Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments) and 40 CFR Part 40 (Research and Demonstration Grants).  Applicable OMB Circulars include: OMB Circular A-21 (Cost Principles for Educational Institutions) relocated to 2 CFR Part 220, OMB Circular A-87 (Cost Principles for State, Local and Indian Tribal Governments) relocated to 2 CFR Part 225, and OMB Circular A-122 (Cost Principles for Non-Profit Organizations) relocated to 2 CFR Part 230.

D. Specific Research Areas of Interest/Expected Outputs and Outcomes
Note to applicant:  The term “output” means an environmental activity or effort, and associated work products, related to a specific environmental goal(s), (e.g., testing a new methodology), that will be produced or developed over a period of time under the agreement. The term “outcome” means the result, effect, or consequence that will occur from the above activit(ies) that is related to an environmental or health-related objective.

The goals of this RFA are to support Centers for research and development of Organotypic Culture Models (OCMs) that:

  1. Capture complex cell-cell and cell-extracellular matrix interactions;
  2. Provide innovative 3D tissue mimetics or microphysiological systems;
  3. Advance the understanding of the underlying pathophysiology and multicellular consequences linking molecular initiating events to AOPs relevant to chemical risks;
  4. Lead to mid- to high-throughput assays capturing physiological responses to chemicals or their metabolites;
  5. Simulate complex biological systems’ response to chemical substances.

The overall Center proposal will be evaluated for its cohesive integration of individual Research Projects to comprehensively address the following research questions: 

  1. What approach will be utilized to develop organotypic cell models that recapitulate specific aspects of normal physiology, and what techniques will be used to characterize the in vitro model system in comparison to the in vivo counterpart? EPA is particularly interested in systems that include characterization of the molecular and cellular pathways perturbed by environmental chemicals.
  2. How will Adverse Outcome Pathways (AOP) based models be developed that allow for quantitative measurement of linkages between molecular initiating events and relevant adverse outcomes, including key events that require the dynamics of a 3D culture?  How will your OCMs be employed to establish linkages between molecular initiating events and adverse outcomes relevant to risk assessment and environmental management decisions (i.e., disease or dysfunction in humans, impacts on survival, growth, and/or reproduction in non-human organisms), and what metrics will be used to establish their certainty?
  3. What steps will be taken towards developing and implementing approaches and techniques to characterize the dosimetry of a chemical substance, including nanomaterials, as they relate to pathway perturbation, both as a function of stressor severity (e.g., dose) and duration or timing of the perturbation? 
  4. By what innovations will proposed OCMs be made amenable to medium or high throughput screening assays?

Proposals should focus on collaborative efforts towards state-of-the-art assay development and data generation. The use of innovative research approaches is encouraged. For example, areas that are not currently covered by OCMs would be ideal for new assay development, or ‘organ-on-a-chip’ microdevices fabricated to enable microfluidics for oxygenation and transport into the underlying microvascular channels. Areas of pursuit may include characterization of relative risk from specific chemicals or chemical classes, or characterization of susceptibility associated with risks from lifestage-specific exposure to chemicals. Refer to the following web link for list of chemicals of potential interest based on EPA’s computational toxicology research program ToxCast™ Chemicals. The ToxCast library of compounds will be made available for screening in the proposed OCMs.

Outputs from the proposed Center may include:

  1. Innovative advanced cell culture techniques that can recapitulate organ system structures and exhibit finely differentiated responses to environmental exposures.
  2. Complex cell or tissue culture models which can characterize the physical and chemical properties that influence pharmacokinetics, bioavailability, and bioactivity of adverse biological effects of chemicals toxicity specific to organ systems.  
  3. Description of biomarkers which can link key dynamic cellular changes resulting from chemical exposure to organ system or higher level in vivo effects.
  4. Refined characterization of the complex relationship between specific environmental chemical stressor exposure, internal dose, and adverse outcomes.

Products expected from the research funded under this RFA are expected to support multi-scale computational modeling and simulation efforts that make use of the data generated to investigate chemical effects on complex cellular interactions and extrapolation to tissue-level consequences in vivo. Outputs may include data, tools and approaches that address fundamental processes underlying higher-order alterations (e.g., disruption of cellular morphogenesis or differentiation leading to adverse developmental outcomes; endocrine-disruptive pathways leading to adverse reproductive outcomes). Of particular interest are outputs that can be used to capture information on molecular initiating events and key cellular events that reconstruct AOPs relevant to toxicological endpoints.

Outcomes from the proposed Center may include:

  1. Better identification of key connections in the continuum between the production of chemical substances and adverse outcomes in humans so that sustainable approaches can be scaled up for risk management purposes.  
  2. More reliable identification and delineation of toxicity pathways from biologic interactions at target tissues or early cellular changes that lead to cell injury and systemic perturbations.
  3. Transformation of chemical toxicity testing that takes advantage of advances in biology and computer modeling to reduce reliance on whole animal toxicity testing while at the same time providing for more efficient and cost-effective methods for characterizing hazards (or lack thereof) associated with the thousands of environmental chemicals lacking toxicity data.
  4. Implementation of quantitative risk assessment techniques that reduce uncertainties in extrapolation from in vitro systems to in vivo outcomes.
  5. Improved understanding of the control of complex biological systems through autocrine, paracrine, and endocrine modes of regulation.

Results of the research are expected to provide: (1) a better understanding of the mechanisms by which cell-level effects may propagate into tissue-level consequences; (2) new hypotheses to formally guide novel experiments aiming to qualify OCM performance; (3) complex models for linking molecular pathways and to complex arrangements of cells and ultimately to distinct AOPs; and (4) better ways to assess the impacts of exposure to chemicals at various life-stages and scales of biological organization.

To the extent practicable, research proposals must embody innovation.  Innovation, for the purposes of this RFA, is defined as the process of making changes; a new method, custom or device.  Innovative research can take the form of wholly new applications or applications that build on existing knowledge and approaches for new uses.  Research proposals must include a discussion on how the proposed research is innovative (see Section IV.B.6).  ORD will draw from the above-mentioned innovation definition in the review/evaluation process of recommending research proposals (see Section V.A).

E. References

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  2. Griffith, L.G., and Swartz, M.A. Capturing complex 3D tissue physiology in vitro. Nature Rev 7: 211-224 (2006).
  3. Yamada, K.M., and Cukierman, E. Modeling tissue morphogenesis and cancer in 3D. Cell 130: 601-610 (2007).
  4. Inglese, J., Johnson, R.L., Simeonov, A., Xia, M., Zheng, W., Austin, C.P., Auld D.S. High-throughput screening assays for the identification of chemical probes. Nature Chem Biol 3: 466-479 (2007).
  5. Judson, R.S., Houck, K.A., Kavlock, R.J., Knudsen, T.B., Martin, M.T., Mortensen, H.M., Reif, D.M., Rotroff, D.M., Shah, I., Richard, A.M., and Dix, D.J. In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project. Environ Health Persp 118: 485-492 (2010).
  6. National Research Council. Toxicity Testing in the 21st Century, A Vision and a Strategy. The National Academies Press, Washington, DC (2007).
  7. Ankley, G.T., Bennett, R.S., Erickson, R.J., Hoff, D.J., Hornung, M.W., Johnson, R.D., Mount, D.R., Nichols, J.W., Russom, C.L., Schmieder, P.K., Serrrano, J.A., Tietge, J.E., and Villeneuve, D.L. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29: 730-741(2010).
  8. Abbott, B.D., and Birnbaum, L.S. TCDD exposure of human embryonic palatal shelves in organ culture alters the differentiation of medial epithelial cells. Teratology 43: 119-132 (1991).
  9. Huang, C., and Hales, B.F. Teratogen responsive signaling pathways in organogenesis stage mouse limbs. Reprod Toxicol. 27: 103-110 (2009).
  10. Stoppini, L., Buchs, P.A., and Muller, D. A simple method for organotypic cultures of nervous tissue. J Neuro Meth 37: 173-182 (1991).
  11. Kim, Y., and Rajagopalan, P. 3D Hepatic Cultures Simultaneously Maintain Primary Hepatocyte and Liver Sinusoidal Endothelial Cell Phenotypes. PLoS ONE 5(11): e15456 (2010).
  12. Weaver, V.M., Petersen, O.W., Wang, F., Larabell, C.A., Briand, P., Damsky, C., and Bissell, M.L. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol 137: 231–245 (1997).
  13. Krause, S., Maffini, M.V., Soto, A.M., and Sonnenschein, C. The microenvironment determines the breast cancer cells' phenotype: organization of MCF7 cells in 3D cultures. BMC Cancer 10: 263 (2010).
  14. van de Kamp, J., Kramann, R., Anraths, J., Schöler, H.R., Ko, K., Knüchel, R., Zenke, M., Neuss, S., and Schneider, R.K. Epithelial morphogenesis of germline-derived pluripotent stem cells on organotypic skin equivalents in vitro. Differentiation 83: 138-147.
  15. Domansky, K., Inman, W., Serdy, J., Dash, A., Lim, M.H., and Griffith, L.G. Perfused multiwell plate for 3D liver tissue engineering. Lap Chip 10: 51-58 (2010).
  16. Huh, D., Matthews, B.D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y., and Ingber, D.E. Reconstituting organ-level lung functions on a chip. Science 328: 1662-1668 (2010).
  17. Knudsen, T.B., and Kleinstreuer, N.C. Disruption of embryonic vascular development in predictive toxicology. Birth Defects Res C 93: 312-323 (2012).
  18. Thomas , R.S., Black, M.B., Li, L., Healy, E.,Chu,T-M., Bao, W., Andersen, M.E. and Wolfinger, R.D. (2012). A Comprehensive Statistical Analysis of Predicting In Vivo Hazard Using High-Throughput In Vitro Screening  Toxicol. Sci. (2012) 128(2): 398-417 doi:10.1093/toxsci/kfs159
  19. Dix DJ, Houck KA, Judson RS, Kleinstreuer NC, Knudsen TB, Martin MT, Reif DM, Richard AM, Shah I, Sipes NS, Kavlock RJ.  Incorporating biological, chemical, and toxicological knowledge into predictive models of toxicity.  Toxicol Sci. 2012 Dec;130(2):440-1; author reply 442-3. doi: 10.1093/toxsci/kfs281.
  20. Sayes CM, Reed KL, Warheit DB. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci 2007, 97: 163-180.
  21. U.S. Environmental Protection Agency, (2009).  The U.S. Environmental Protection Agency’s Strategic Plan for Evaluating the Toxicity of Chemicals.
 

F. Special Requirements
Agency policy and ethical considerations prevent EPA technical staff and managers from providing applicants with information that may create an unfair competitive advantage.  Consequently, EPA employees will not review, comment, advise, and/or provide technical assistance to applicants preparing applications in response to EPA RFAs.  EPA employees cannot endorse any particular application.

Multiple Investigator applications may be submitted as: (1) a single Lead Principal Investigator (PI) application with Co-PI(s) or (2) a Multiple PI application (with a single Contact PI).  Multiple PI applications must follow the specific instructions provided in Sections IV. and V. of this RFA.  For further information, please see the EPA Implementation Plan for Policy on Multiple Principal Investigators (Research Business Models Working Group).

Groups of two or more eligible applicants may choose to form a Center and submit a single application for this assistance agreement. Applications must identify which organization will be the recipient of the assistance agreement and which organizations(s) will be subawardees of the recipient.  Partnerships and collaborations are strongly encouraged and will be evaluated as part of the peer review evaluation under Section V.  For applicants proposing a subgrant(s) in the application, please see Section IV.B.12 of this solicitation for budget information and refer to Contracts and Subawards.

This solicitation provides the opportunity for the submission of applications for projects that may involve human subjects research.  There are many scientific and ethical considerations that must be addressed in such studies by the study sponsor and research team, including, but not limited to, those related to recruitment, retention, participant compensation, third-party issues, researcher-participant interactions, researcher-community interactions, communications, interventions, and education.  All such research must comply with the requirements of 40 CFR Part 26, and any human observational exposure studies must also adhere to the principles set forth in the Scientific and Ethical Approaches for Observational Exposure Studies (SEAOES) (EPA/600/R-08/062) (PDF) (133 pp, 1.21 MB) document.  SEAOES, which was published by researchers in EPA and which discusses the principles for the ethical conduct of human research studies, serves as a resource for applicants interested in applying under this solicitation.  References to “SEAOES Principles” in this solicitation refers, in general, to the issues of interest in conducting human subjects research studies that maintain the highest scientific and ethical standards and safety during the conduct of these studies.  All applications must include a Human Subjects Research Statement (HSRS; described in Section IV.B.8) and if the project involves human subjects research, it will be subject to an additional level of review prior to funding decisions being made as described in Sections V.C and V.D of this solicitation. Under EPA Regulation 40 CFR Part 26 (Protection of Human Subjects) covering the Common Rule, human cell lines are not covered in the definition of human subjects. 

The application shall include a plan (see “Data Plan” in section IV.B.9) to make available to the NCER project officer all data generated (first produced under the award) from observations, analyses, or model development used under an agreement awarded from this RFA.  The data must be available in a format and with documentation such that they may be used by others in the scientific community.

As described more fully in Section IV, each application should address the following items (for content and form of application submission and page limitations, see Section IV.B).

  1. Center Description (5-page limit): Applications should describe the overall goals, objectives, and approach for the Center, including how the Center will pursue multidisciplinary, comprehensive, and thematic research. The Center description should demonstrate how the various projects contained within the Center are integrated. The qualities of Research Projects should complement each other and reflect the Center’s overall approach. The Center description must describe the expertise and qualifications of participating investigators and discuss the complementary support provided by each member and partner.

    The application should describe how the Center’s work will produce complex cell or tissue culture models which can characterize the physical and chemical properties that influence pharmacokinetics, bioavailability, and bioactivity of adverse biological effects of chemicals toxicity specific to organ systems.  The proposed efforts should seek innovative solutions that identify key connections in the continuum between the production of chemical substances and adverse outcomes in humans. The application should also describe the Center’s commitment to transforming chemical toxicity testing that takes advantage of advances in biology and computer modeling.

     
  2. Research Project Descriptions (15-page limit for each project description):  Applications should contain a maximum of five projects that address the research questions described above in Section I.D.  Each of the specific individual research projects should be completely described according to the instructions in Section IV below.  Individual project descriptions should explain how the project fits into the overall Center’s program and relates to other projects in the application.

  3. Administrative Unit Description (15-page limit):  The Center shall have an Administrative Unit which provides oversight, coordination and integration of the Center’s activities. Describe how the Administrative Unit will coordinate the research activities and how the program will be integrated internally. Center proposals should take a multidisciplinary approach and indicate how programmatic and funding decisions will be made; how project objectives will be successfully achieved in a timely manner in accordance with project schedules and milestones; how investigators from different disciplines within the Center will communicate on a regular basis about the development and progress of Center projects; how progress toward achieving the expected results (outputs and outcomes) will be monitored and measured; who will set priorities and who will ensure the quality of the research. The approach, procedures, and controls for ensuring that awarded grant funds will be expended in a timely and efficient manner should also be described. In conducting its research, the Center should apply measures of success or progress, including developing and promoting the use of statistically valid protocols to evaluate program effectiveness and applying metrics to evaluate the project’s success, progress, or effectiveness.

 

II. AWARD INFORMATION

It is anticipated that a total of approximately $18 million will be awarded under this announcement, depending on the availability of funds, quality of applications received, and other applicable considerations. The EPA anticipates funding approximately 3 awards under this RFA.  Requests for amounts in excess of a total of $6,000,000, including direct and indirect costs, will not be considered. The total project period requested in an application submitted for this RFA may not exceed 4 years. 

The EPA reserves the right to reject all applications and make no awards, or make fewer awards than anticipated, under this RFA.  The EPA reserves the right to make additional awards under this announcement, consistent with Agency policy, if additional funding becomes available after the original selections are made. Any additional selections for awards will be made no later than six months after the original selection decisions.

In appropriate circumstances, EPA reserves the right to partially fund proposals/applications by funding discrete portions or phases of proposed projects. If EPA decides to partially fund a proposal/application, it will do so in a manner that does not prejudice any applicants or affect the basis upon which the proposal/application, or portion thereof, was evaluated and selected for award, and therefore maintains the integrity of the competition and selection process.

EPA may award both grants and cooperative agreements under this announcement.

Under a grant, EPA scientists and engineers are not permitted to be substantially involved in the execution of the research.  However, EPA encourages interaction between its own laboratory scientists and grant Principal Investigators after the award of an EPA grant for the sole purpose of exchanging information in research areas of common interest that may add value to their respective research activities.  This interaction must be incidental to achieving the goals of the research under a grant.  Interaction that is “incidental” does not involve resource commitments.

Where appropriate, based on consideration of the nature of the proposed project relative to the EPA’s intramural research program and available resources, the EPA may award cooperative agreements under this announcement.  When addressing a research question/problem of common interest, collaborations between EPA scientists and the institution’s principal investigators are permitted under a cooperative agreement.  These collaborations may include data and information exchange, providing technical input to experimental design and theoretical development, coordinating extramural research with in-house activities, the refinement of valuation endpoints, and joint authorship of journal articles on these activities.  Proposals may not identify EPA cooperators or interactions; specific interactions between EPA’s investigators and those of the prospective recipient for cooperative agreements will be negotiated at the time of award.

III. ELIGIBILITY INFORMATION

A. Eligible Applicants
Public nonprofit institutions/organizations (includes public institutions of higher education and hospitals) and private nonprofit institutions/organizations (includes private institutions of higher education and hospitals) located in the U.S., state and local governments, Federally Recognized Indian Tribal Governments, and U.S. territories or possessions are eligible to apply.  Profit-making firms are not eligible to receive assistance agreements from the EPA under this program.

Eligible nonprofit organizations include any organizations that meet the definition of nonprofit in OMB Circular A-122, located at 2 CFR Part 230.  However, nonprofit organizations described in Section 501(c) (4) of the Internal Revenue Code that lobby are not eligible to apply.

Foreign governments, international organizations, and non-governmental international organizations/institutions are not eligible to apply.

National laboratories funded by Federal Agencies (Federally-Funded Research and Development Centers, “FFRDCs”) may not apply.  FFRDC employees may cooperate or collaborate with eligible applicants within the limits imposed by applicable legislation and regulations.  They may participate in planning, conducting, and analyzing the research directed by the applicant, but may not direct projects on behalf of the applicant organization.  The institution, organization, or governance receiving the award may provide funds through its assistance agreement from the EPA to an FFRDC for research personnel, supplies, equipment, and other expenses directly related to the research.  However, salaries for permanent FFRDC employees may not be provided through this mechanism.

Federal Agencies may not apply.  Federal employees are not eligible to serve in a principal leadership role on an assistance agreement, and may not receive salaries or augment their Agency’s appropriations in other ways through awards made under this program.

The applicant institution may enter into an agreement with a Federal Agency to purchase or utilize unique supplies or services unavailable in the private sector to the extent authorized by law.  Examples are purchase of satellite data, chemical reference standards, analyses, or use of instrumentation or other facilities not available elsewhere.  A written justification for federal involvement must be included in the application.  In addition, an appropriate form of assurance that documents the commitment, such as a letter of intent from the Federal Agency involved, should be included.

Potential applicants who are uncertain of their eligibility should contact Ron Josephson (josephson.ron@epa.gov) in NCER, phone: 703-308-0442.

B. Cost-Sharing
Institutional cost-sharing is not required.

C. Other
Applications must substantially comply with the application submission instructions and requirements set forth in Section IV of this announcement or they will be rejected.  In addition, where a page limitation is expressed in Section IV with respect to parts of the application, pages in excess of the page limit will not be reviewed.  Applications must be submitted through grants.gov or by other authorized alternate means (see Section IV.E. “Submission Instructions and Other Submission Requirements” for further information) on or before the solicitation closing date and time in Section IV of this announcement or they will be returned to the sender without further consideration.  Also, applications exceeding the funding limits or project period term described herein will be returned without review.  Further, applications that fail to demonstrate a public purpose of support or stimulation (e.g., by proposing research which primarily benefits a Federal program or provides a service for a Federal agency) will not be funded. 

Applications which include more than five research projects will be deemed ineligible.

Applications deemed ineligible for funding consideration will be notified within fifteen calendar days of the ineligibility determination.

IV. APPLICATION AND SUBMISSION INFORMATION

Additional provisions that apply to this solicitation and/or awards made under this solicitation, including but not limited to those related to confidential business information, contracts and subawards under grants, and proposal assistance and communications, can be found at Fiscal Year 2010 Competitive Grant Awards

These, and the other provisions that can be found at the website link, are important, and applicants must review them when preparing applications for this solicitation.   If you are unable to access these provisions electronically at the website above, please communicate with the EPA contact listed in this solicitation to obtain the provisions.

Formal instructions for submission through Grants.gov follow in Section E.

A. Internet Address to Request Application Package
Use the application package available at Grants.gov (see Section E. “Submission Instructions and Other Submission Requirements”).  Note: With the exception of the current and pending support form (available at Forms and Standard Instructions Download Page), all necessary forms are included in the electronic application package.

An email will be sent by NCER to the Lead/Contact PI and the Administrative Contact (see below) to acknowledge receipt of the application and transmit other important information.  The email will be sent from receipt.application@epa.gov; emails to this address will not be accepted.  If you do not receive an email acknowledgment within 30 days of the submission closing date, immediately inform the Eligibility Contact shown in this solicitation.  Failure to do so may result in your application not being reviewed.  See Section E. “Submission Instructions and Other Submission Requirements” for additional information regarding the application receipt acknowledgment.

B. Content and Form of Application Submission
The application is made by submitting the materials described below.  Applications must contain all information requested and be submitted in the formats described.  

Summary of Page and other Limitations for Application Content:

Descriptions must be single-spaced on 8.5x11-inch pages, with standard 12-point type and 1-inch margins.  While these guidelines establish the minimum type size requirements, applicants are advised that readability is of paramount importance and should take precedence in selection of an appropriate font for use in the proposal.

The following page limitations may not be exceeded (excess pages will not be reviewed):

  • Abstracts: 1-page abstract for the Center as a whole; 1-page abstracts for each proposed research project (no more than 5 project proposals are to be submitted)
  • Center Description: 5 pages
  • Research Plan(s): 15 pages for each research project description (no more than 5 project proposals are to be submitted)
  • Quality Management Plan: 5 pages
  • Human Subjects Research Statement: 6 pages
  • Data Plan: 2 pages
  • Administrative Unit: 15 pages
  • Budget Justification: 2 pages per research project; 2 pages for the Administrative Unit
  1. Standard Form 424

    The applicant must complete Standard Form 424. Instructions for completion of the SF424 are included with the form. (However, note that EPA requires that the entire requested dollar amount appear on the SF424, not simply the proposed first year expenses.) The form must contain the signature of an authorized representative of the applying organization.

    Applicants are required to provide a “Dun and Bradstreet Data Universal Numbering System” (DUNS) number when applying for federal grants or cooperative agreements. Organizations may receive a DUNS number by calling 1-866-705-5711 or by visiting the web site at Dun and Bradstreet Exit EPA Click for Disclaimer.

    Executive Order 12372, “Intergovernmental Review of Federal Programs,” does not apply to the Office of Research and Development's research and training programs unless EPA has determined that the activities that will be carried out under the applicants' proposal (a) require an Environmental Impact Statement (EIS), or (b) do not require an EIS but will be newly initiated at a particular site and require unusual measures to limit the possibility of adverse exposure or hazard to the general public, or (c) have a unique geographic focus and are directly relevant to the governmental responsibilities of a State or local government within that geographic area.

    If EPA determines that Executive Order 12372 applies to an applicant's proposal, the applicant must follow the procedures in 40 CFR Part 29. The applicant must notify their state's single point of contact (SPOC). To determine whether their state participates in this process, and how to comply, applicants should consult Intergovernmental Review (SPOC List). If an applicant is in a State that does not have a SPOC, or the State has not selected research and development grants for intergovernmental review, the applicant must notify directly affected State, area wide, regional and local entities of its proposal.

    EPA will notify the successful applicant(s) if Executive Order 12372 applies to its proposal prior to award.

  2. Key Contacts

    The applicant must complete the “Key Contacts” form found in the Grants.gov application package. An “Additional Key Contacts” form is also available at Forms and Standard Instructions Download Page. The Key Contacts form should also be completed for major sub-agreements (i.e., primary investigators). Do not include information for consultants or other contractors. Please make certain that all contact information is accurate.

    For Multiple PI applications: The Additional Key Contacts form must be completed (see Section I.F. for further information). Note: The Contact PI must be affiliated with the institution submitting the application. EPA will direct all communications related to scientific, technical, and budgetary aspects of the project to the Contact PI; however, any information regarding an application will be shared with any PI upon request. The Contact PI is to be listed on the Key Contact Form as the Project Manager/Principal Investigator (the term Project Manager is used on the Grants.gov form, the term Principal Investigator is used on the form located on NCER’s web site). For additional PIs, complete the Major Co-Investigator fields and identify PI status next to the name (e.g., “Name: John Smith, Principal Investigator”).

  3. Table of Contents

    Provide a list of the major subdivisions of the application indicating the page number on which each section begins.

  4. Abstract (1 page abstract for the Center as a whole; 1 page abstracts for each proposed research project)

    The abstract is a very important document in the review process. Therefore, it is critical that the abstract accurately describes the research being proposed and conveys all the essential elements of the research. Also, the abstracts of applications that receive funding will be posted on the NCER web site.

    The abstract should include the information described below (a-h). Examples of abstracts for current grants may be found on the NCER web site.

    1. Funding Opportunity Title and Number for this proposal.
    2. Project Title: Use the exact title of your project as it appears in the application. The title must be brief yet represent the major thrust of the project. Because the title will be used by those not familiar with the project, use more commonly understood terminology. Do not use general phrases such as “research on.”
    3. Investigators: For applications with multiple investigators, state whether this is a single Lead PI (with co-PIs) or Multiple PI application (see Section I.F.). For Lead PI applications, list the Lead PI, then the name(s) of each co-PI who will significantly contribute to the project. For Multiple PI applications, list the Contact PI, then the name(s) of each additional PI. Provide a web site URL or an email contact address for additional information.
    4. Institution(s): In the same order as the list of investigators, list the name, city and state of each participating university or other applicant institution. The institution applying for assistance must be clearly identified.
    5. Project Period and Location: Show the proposed project beginning and ending dates and the performance site(s)/geographical location(s) where the work will be conducted.
    6. Project Cost: Show the total funding requested from the EPA (include direct and indirect costs for all years).
    7. Project Summary: Provide three subsections addressing: (1) the objectives of the study (including any hypotheses that will be tested), (2) the experimental approach to be used (a description of the proposed project), and (3) the expected results (outputs/outcomes) of the project and how it addresses the research needs identified in the solicitation, including the estimated improvement in risk assessment or risk management that will result from successful completion of the proposed work.
    8. Supplemental Keywords: Without duplicating terms already used in the text of the abstract, list keywords to assist database searchers in finding your research. A list of suggested keywords may be found at: Forms and Standard Instructions Download Page.
  5. Center Description (5 pages)

    Applications should describe the overall goals, objectives, and approach for the Center, including how the Center will pursue multidisciplinary, comprehensive, and thematic research. The Center description should demonstrate how the various projects contained within the Center are integrated. The qualities of Research Projects should complement each other and reflect the Center’s overall approach. The Center description must describe the expertise and qualifications of participating investigators and discuss the complementary support provided by each member and partner.

    The application should describe how the Center’s work will produce complex cell or tissue culture models which can characterize the physical and chemical properties that influence pharmacokinetics, bioavailability, and bioactivity of adverse biological effects of chemicals toxicity specific to organ systems. The proposed efforts should seek innovative solutions that identify key connections in the continuum between the production of chemical substances and adverse outcomes in humans. The application should also describe the Center’s commitment to transforming chemical toxicity testing that takes advantage of advances in biology and computer modeling.

  6. Research Project Plan Descriptions (15 pages per research project description)

    Applications may include up to five projects that address the research questions in Section I.D. Projects should focus on a limited number of research objectives that adequately and clearly demonstrate that they meet the RFA requirements, and are integrated to respond to the Center’s objectives as a whole. Explicitly state the main hypotheses that you will investigate, the data you will create or use, the analytical tools you will use to investigate these hypotheses or analyze these data, and the results you expect to achieve. Research methods must be clearly stated so that reviewers can evaluate the appropriateness of your approach and the tools you intend to use. A statement such as: “we will evaluate the data using the usual statistical methods” is not specific enough for peer reviewers.

    The description must provide the following information:

    1. Objectives: List the objectives of the proposed research and the hypotheses being tested during the project, and briefly state why the intended research is important and how it fulfills the requirements of the solicitation. This section should also include any background or introductory information that would help explain the objectives of the study. If this application is to expand upon research supported by an existing or former assistance agreement awarded under the STAR program, indicate the number of the agreement and provide a brief report of progress and results achieved under it.
    2. Approach/Activities: Outline the research design, methods, and techniques (including quality assurance/quality control protocols) that you intend to use in meeting the objectives stated above.
    3. Innovation: Describe how your project shifts current research or engineering paradigms by using innovative theoretical concepts, approaches or methodologies, instrumentation or interventions applicable to one or more fields of research.
    4. Expected Results, Benefits, Outputs, and Outcomes: Describe the results you expect to achieve during the project (outputs) and the potential benefits of the results (outcomes). This section should also discuss how the research results will lead to solutions to environmental problems and improve the public’s ability to protect the environment and human health. A clear, concise description will help NCER and peer reviewers understand the merits of the research.
    5. General Project Information: Discuss other information relevant to the potential success of the project. This should include facilities, personnel expertise/experience (including the unique contributions of each member or partner in the project to achieving the overall purpose and objectives of the research), project schedules with associated milestones and target dates, proposed management, interactions with other institutions, etc. Applications for multi-investigator projects must identify project management and the functions of each investigator in each team and describe plans to communicate and share data.
    6. Appendices may be included but must remain within the 15-page limit.
  7. Quality Management Plan (5 pages)

    For projects involving data collection or processing, environmental measurements, modeling, or the development of environmental technology for pollution control (whether hardware-based or via new techniques), the EPA requires a Quality Management Plan (QMP) describing the Center’s policies and procedures that assure research results satisfy the intended objectives. The Quality Management Plan provided with the application must contain, at a minimum the information below. EPA will likely require an expanded version of this document following award.

    1. Summary - A discussion of the overall quality assurance and quality control needs of the Center and the objectives of their Quality Assurance and Quality Control (QA/QC) policy.
    2. Organization and Management - This section should include:
      1. Organization chart that identifies by name:
        1. all of the components (research project or unit activity) of the Center;
        2. the Principal Investigator or overall manager for each component;
        3. the QA Manager who oversees the quality system for the Center, and how the QA manager reports to the Center Director or lead PI;
        4. the person(s) responsible for QA/QC activities for each component and how they report to the QA Manager.
      2. Description of the specific responsibilities of the QA Manager and any other personnel with QA responsibilities;
      3. Description of any delegations of QA responsibility to sub-awardees or contractors (especially QC responsibilities); and
      4. Discussion of how the Center will maintain effective communications throughout the management structure.
    3. Quality System - This section should include brief discussions of:
      1. How the Center’s research activities will be reviewed and evaluated to ensure quality;
      2. How staff will be trained, and who will be responsible for training and oversight of QA practices during conduct of the research;
      3. How data will be stored and made available to Center personnel and to the public; and
      4. How the Center’s QA/QC procedures will be reviewed and evaluated, including how recommended changes will be implemented.
    4. Project or Component Specific - This section should discuss the QA and QC needs for the Center’s components and should describe or reference any standard procedures (such as SOPs) that will be used to address these needs. (Individual project QA plans, expected after award as part of the Center’s QA program, should include detailed descriptions of how the data needs relate to the hypotheses being tested or the objectives.) This section should also address the following:
      1. How the sample size(s) will be selected and demonstrated to be sufficient to test the hypotheses or meet a specific objective;
      2. How the necessary performance criteria for measured data to test the hypotheses or meet the objective will be identified;
      3. How the quality of previously collected data will be determined appropriate for its stated use;
      4. How data will be managed (collected, backed-up, collated, transferred, and stored) to ensure that the quality is maintained and documented; and
      5. What data analysis methods will be used.
    5. Documentation and Records - Describe or reference the procedures the Center will use for identifying and maintaining QA and QC related documents and records.

    General QMP guidance can be found at NCER’s Guidance for Quality Management Plans (QMPs) General Guidance for Writing and Reviewing QMPs For EPA/NCER and the STAR Grant Program (PDF) (2pp, 25 K)

    For more detailed EPA guidance, see EPA Requirements for Quality Management Plans (EPA QA/R-2) (PDF) (30 pp, 87 K) on EPA website.

  8. EPA Human Subjects Research Statement (HSRS) (6 pages)

    All human research studies conducted or supported by EPA are governed by EPA regulations at 40 CFR Part 26 (Protection of Human Subjects). This includes the Basic Federal Policy for the Protection of Human Research Subjects, also known as the Common Rule, at subpart A and additional prohibitions and special protections for pregnant women, nursing women, and children in research conducted or supported by EPA at subparts B, C, and D. Depending upon the type of research being conducted, additional subparts of 40 CFR Part 26 may be relevant.

    Procedures for the review and oversight of human research subject to 40 CFR Part 26 are also provided in EPA Order 1000.17 Change A1 (PDF) (41 pp, 333 K). These include review of projects for EPA-supported human research by the EPA Human Subjects Research Review Official (HSRRO). EPA Order 1000.17 Change A1 requires preliminary approval by the HSRRO of all proposed EPA-supported human research before the agreement can be entered into. Additional requirements must be met and final approval received from the HSRRO before the research can begin. When reviewing human observational exposure studies, EPA Order 1000.17 Change A1 requires the HSRRO to apply the principles described in the SEAOES (PDF) (133 pp, 1.21 MB) document and grant approval only to studies that adhere to those principles.

    All applications submitted under this solicitation must include a HSRS as described below. Please use the definitions below to determine whether the proposed research involves human subjects, and then prepare a HSRS as explained below in the “HSRS Requirements” section.

    Definitions (from 40 CFR Part 26 Subparts A, B, and C) to determine the involvement of human subjects in proposed research:

    • "Human subject" means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.
    • "Intervention" includes both physical procedures by which data are gathered and manipulations of the subject or the subject's environment that are performed for research purposes.
    • "Interaction" includes communication or interpersonal contact between investigator and subject.
    • "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 which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).
    • "Individually identifiable" means the identity of the subject is or may readily be ascertained by the investigator or associated with the information.
    • "Research involving the intentional exposure of a human subject" means a study of a substance in which the exposure to the substance experienced by a human subject participating in the study would not have occurred but for the human subject’s participation in the study. Research involving intentional human exposures have additional requirements based upon the 2004 NRC Report “Intentional Human Dosing Studies for EPA Regulatory Purposes” Exit EPA Click for Disclaimer See Sections 9 - 15.
    • "Observational research" means any human research that does not meet the definition of research involving intentional exposure of a human subject.

    Human Subjects Research Statement (HSRS) Requirements

    If the proposed research does not involve human subjects as defined above, provide the following statement in your application package as your HSRS: “The proposed research does not involve human subjects.” Applicants should provide a clear justification about how the proposed research does not meet the definition (for example, all samples come from deceased individuals OR samples are purchased from a commercial source and provided without identifiers, etc.).

    If the proposed research does involve human subjects, then include in your application package a HSRS that addresses each applicable section listed below, referencing the specific location of the information in the Research Plan, providing the information in the HSRS, or explaining why the section does not apply to the proposed research. (Not all will apply.) Please use the definitions provided above to ensure consistency in the interpretation of terminology. Do not exceed six consecutively numbered, 8.5x11-inch pages of single-spaced, standard 12-point type with 1-inch margins.

    NOTE: Before EPA approves any research involving human subjects, the requirements of the regulations at 40 CFR Part 26 must be met. Also, before EPA approves human observational exposure research, EPA will examine it to ensure consistency with the SEAOES Principles. The federal Office for Human Research Protections requires that federally funded human subjects research only be conducted at facilities covered by a Federalwide Assurance (FWA). An FWA is a document that designates the Institutional Review Board that will review and oversee the research, specifies the ethical principles under which the research will be conducted, and names the individuals who will be responsible for the proper conduct of the research. The factors below are not intended to be exhaustive of all those needed for the HSRRO to provide the final approval necessary for research to be conducted, but provide a basis upon which the HSRRO may grant the conditional approval necessary for the funding process to begin.

    Items 1 – 8 must be completed for all studies involving human subjects. (For studies involving intentional exposures, also complete Items 9 -15.)

    1. Human subjects involvement, characteristics, and design.
      1. Describe and justify the proposed involvement of human subjects in the work being proposed.
      2. Describe the characteristics of the subject population, including their anticipated number, age range, and health status if relevant.
      3. Describe and justify the sampling plan, as well as the recruitment and retention strategies and the criteria for inclusion or exclusion of any subpopulations.
      4. Describe the research material that will be obtained from or about living individuals in the form of data, specimens, or records.
      5. List any collaborating sites where human subjects research will be performed, and describe the role of those sites and collaborating investigators in the research.
      6. Describe and justify any compensation being provided to subjects for their participation in the research.
      7. Describe the plan for communicating individual and/or aggregate research results to participants, if relevant.
    2. Potential risks to subjects.
      1. Describe the potential risks to human subjects (physical, psychological, financial, legal, or other) and assess their likelihood and seriousness to the human subjects.
    3. Adequacy of protection against risks.
      1. Describe planned procedures for protecting against or minimizing potential risks and assess their likely effectiveness.
      2. Describe planned procedures for the process of obtaining and maintaining informed consent. Include a description of the circumstances under which consent will be sought and obtained, who will seek it, the nature of the information to be provided to prospective subjects, and the method of documenting consent.
      3. If waiver of some or all of the elements of informed consent or of documentation of consent will be sought, provide justification for the waiver.
      4. Where appropriate, discuss the plans for ensuring necessary medical or professional intervention in the event of adverse effects to subjects.
    4. Protection of vulnerable groups, see 40 CFR Part 26, subparts C & D.
      1. Explain the rationale for the involvement of any vulnerable populations, including pregnant women, fetuses, and children if relevant.
      2. Describe the additional protections in place, if any, for protecting vulnerable populations included in the research.
      3. If children are included in the research, describe the process for obtaining parental permission and child assent if relevant.
    5. Protection of privacy and confidentiality.
      1. Describe how data, specimens, and/or records will be collected, managed, and protected, including at collaborating sites, if any, as well as at the primary site.
      2. Indicate who will have access to individually identifiable private information about human subjects.
      3. Describe any additional procedures for the protection of privacy and confidentiality of the human research subjects.
      4. Discuss any mandatory reporting requirements with the potential to come into play during the conduct of the research and describe how these will be communicated to participants if relevant.
      5. Discuss the potential of the research to obtain information about third parties and describe how this will be handled if it occurs.
    6. Relationship between researcher and community.
      1. If the research will take place in a community setting, describe the procedures in place for defining the community, obtaining its involvement in the research, and establishing and maintaining trust.
    7. Potential benefits of the research to the participants and others.
      1. Discuss the potential benefits of the research to the research participants and others.
      2. Discuss why the risks to subjects are reasonable in relation to the anticipated benefits.
    8. Importance of the knowledge to be gained.
      1. Discuss the importance of the knowledge to be gained as a result of the proposed research.
      2. Discuss why the risks to subjects are reasonable in relation to the importance of the knowledge that reasonably may be expected to result.
    9. The following sections are to be completed for projects involving the intentional exposure of a human subject. Note that intentional exposure of children, pregnant women or nursing women is prohibited, according to 40 CFR Part 26, subpart B. If your proposal does not involve intentional exposures of humans, you may enter “non-applicable” for Sections 9 – 15.

    10. Projects involving intentional exposure of human subjects should only be considered if they have the potential of providing a clear health or environmental benefit or if acquisition of such information is not obtainable by any other means. In no case should the exposure cause lasting harm to study participants.
      1. Provide justification, in advance of being conducted, that the study could contribute to addressing an important scientific question that cannot be resolved on the basis of animal data or other study;
      2. Discuss how the study is designed in accordance with current scientific standards and practices to i) address the research question, ii) include representative study populations for the endpoint in question, and iii) meet requirements for adequate statistical power;
      3. Discuss how the study will be conducted in accordance with recognized good clinical practices, including appropriate monitoring for safety; and
      4. Confirm that the grantee will report comprehensively to their EPA Project Officer, providing the full study protocol, detailed analyses of the data and report any adverse events promptly.
    11. Value of Studies that Seek to Provide a Potential Public Health or Environmental Benefit
      1. Discuss the constitution of the IRB and their ability to consider whether a study has the potential of providing a clear health or environmental benefit to the community.
    12. Criteria for Scientific and Ethical Acceptability
      1. Confirm that the following necessary conditions for scientifically and ethically acceptable intentional human dosing studies have been satisfied:
        1. prior animal studies and, if available, human observational studies;
        2. a demonstrated need for the knowledge to be obtained from intentional human dosing studies;
        3. justification and documentation of a research design and statistical analysis that are adequate to address an important scientific question, including adequate power to detect appropriate effects;
        4. an acceptable balance of risks and benefits, and minimization of risks to participants;
        5. equitable selection of participants;
        6. free and informed consent of participants; and
        7. review by an appropriately constituted IRB.
    13. Participant Selection Criteria
      1. Discuss how the project design ensures that the following conditions are met in selecting research participants: (i) Selection should be equitable; (ii) Selection of persons from vulnerable populations must be convincingly justified in the protocol, which also must justify the measures to be taken to protect those participants; (iii) Selection of individuals with conditions that put them at increased risk for adverse effects in such studies must be convincingly justified in the protocol, which also must justify the measures that investigators will use to decrease the risks to those participants to an acceptable level.
    14. Payment for Participation
      1. Discuss how IRBs, all relevant review boards, investigators, and research sponsors should ensure that payments to participants in intentional human dosing studies are neither so high as to constitute undue inducement nor so low as to be attractive only to individuals who are socio-economically disadvantaged. Proposed levels of and purposes for remuneration (e.g., time, inconvenience, and risk) should be scrutinized in light of the principles of justice and respect for persons.
    15. Best Practices in Informed Consent
      1. Discuss the proposed process regarding informed consent in intentional human dosing studies and how it compares to best practices.
    16. Compensation for Research-Related Injuries
      1. Discuss how you ensure that participants receive needed medical care for injuries incurred in the study, without cost to the participants.
  9. Data Plan (2 pages)

    Provide a plan to make all data resulting from an agreement under this RFA available in a format and with documentation/metadata such that they may be used by others in the scientific community. This includes data first produced under the award, i.e., from observations, analyses, or model development collected or used under the agreement. Applicants who plan to develop or enhance databases containing proprietary or restricted information must provide, within the two pages, a strategy to make the data widely available, while protecting privacy or property rights.

  10. Administrative Unit (15 pages)

    The Center shall have an Administrative Unit which provides oversight, coordination and integration of the Center’s activities. Describe how the Administrative Unit will coordinate the research activities and how the program will be integrated internally. Center proposals should take a multidisciplinary approach and indicate how programmatic and funding decisions will be made; how project objectives will be successfully achieved in a timely manner in accordance with project schedules and milestones; how investigators from different disciplines within the Center will communicate on a regular basis about the development and progress of Center projects; how progress toward achieving the expected results (outputs and outcomes) will be monitored and measured; who will set priorities and who will ensure the quality of the research. The approach, procedures, and controls for ensuring that awarded grant funds will be expended in a timely and efficient manner should also be described. In conducting its research, the Center should apply measures of success or progress, including developing and promoting the use of statistically valid protocols to evaluate program effectiveness and applying metrics to evaluate the project’s success, progress, or effectiveness.

    The administrative unit description should also address how the Center will disseminate research findings and other information. The description should explain how products, research results, and findings will be internally reviewed and then disseminated to stakeholders, as well as how the flow of information among investigators will be facilitated. Publishing research results in scientific journals is essential; however, it is not sufficient. Plans for Center websites, social networks, and other means of communicating results should be described.

    The Center must be led by an overall Director who will provide oversight, coordination, and integration of the Center’s activities. The Director assumes responsibility to maintain contact with and update the EPA Project Officer (PO) regarding progress of research and also provides the PO with timely reporting of operational and or budget issues that may arise. Describe the duties of administrative staff and their qualifications and contributions to the specialized needs and conduct of the Center’s research activities.

  11. References

    References cited are in addition to other page limits (e.g. research plan, quality management plan).

  12. Budget and Budget Justification

    1. Budget

      Prepare a master budget table using “SF-424A Budget Information for Non-Construction Programs” (aka SF-424A), available in the Grants.gov electronic application package and also at Forms and Standard Instructions Download Page. Only complete “Section B-Budget Categories”. Provide the object class budget category (a. - k.) amounts for each budget year under the “Grant Program, Function or Activity” heading. Each column reflects a separate budget year. For example, Column (1) reflects budget year 1. The total budget will be automatically tabulated in column (5).

      Also provide separate SF-424As for each individual research project proposed as well as for the administrative unit. Additional SF-424As may be downloaded at Forms and Standard Instructions Download Page. Attach the additional SF-424As to the Project Narrative (see Section IV.E. “Submission Instructions and Other Submission Requirements”).

      If a subaward is included in the application, provide a separate SF-424A and budget justification for the subaward. Include the total amount for the subaward under “Other” in the master SF-424A.

      Applicants may not use subagreements to transfer or delegate their responsibility for successful completion of their EPA assistance agreement. Therefore, EPA expects that subawards or subcontracts should not constitute more than 40% of the total direct cost of the total project budget. If a subaward/subcontract constitutes more than 40% of the total direct cost, additional justification may be required before award, discussing the need for the subaward/subcontract to accomplish the objectives of the research project. Please refer to Contracts and Subawards if your organization intends to identify specific contractors, including consultants, and subawardees in your proposal.

      Please note that institutional cost-sharing is not required. However, if voluntary cost-sharing is proposed, a brief statement concerning cost-sharing should be added to the budget justification.

    2. Budget Justification [2 pages per research project and the administrative unit, not including additions under No.(7) below to support subawards]

      Describe the basis for calculating the personnel, fringe benefits, travel, equipment, supplies, contractual support, and other costs identified in the SF-424A. Each budget justification should not exceed two consecutively numbered (bottom center), 8.5x11-inch pages of single-spaced, standard 12-point type with 1-inch margins.

      Budget information should be supported at the level of detail described below:

      1. Personnel: List all staff positions by title. Give annual salary, percentage of time assigned to the project, total cost for the budget period, and project role. Compensation paid for employees engaged in grant activities must be consistent with payments for similar work within the applicant organization. Note that for salaries to be allowable as a direct charge to the award, a justification of how that person will be directly involved in the project must be provided. General administrative duties such as answering telephones, filing, typing, or accounting duties are not considered acceptable.

        Below is a sample computation for Personnel:

        Position/Title Annual Salary % of Time Assigned to Project Cost
        Project Manager $70,000 50% $ 35,000
        Env. Specialist $60,000 100% $ 60,000
        Env. Health Tech $45,000 100% $ 45,000
        Total Personnel $140,000

        Note this budget category is limited to persons employed by the applicant organization ONLY. Those employed elsewhere are classified as subawardees, contractors or consultants. Contractors and consultants should be listed under the “Contractual” budget heading while subawards made to eligible subrecipients are listed under the “Other” budget heading.

      2. Fringe Benefits: Identify the percentage used and the basis for its computation. Fringe benefits are for the personnel listed in budget category (1) above and only for the percentage of time devoted to the project. Fringe benefits include but are not limited to the cost of leave, employee insurance, pensions and unemployment benefit plans. The applicant should not combine the fringe benefit costs with direct salaries and wages in the personnel category.

      3. Travel: Specify the estimated number of trips, purpose of each trip, number of travelers per trip, destinations, and other costs for each type of travel. Explain the need for any travel, paying particular attention to travel outside the United States. Include travel funds for annual STAR program progress reviews (estimate for two days in Washington, D.C.) and a final workshop to report on results.

        Below is a sample computation for Travel:

        Purpose of Travel Location Item Computation Cost
        EPA STAR Progress Review DC Lodging 4 people x $100 per night
        x 2 nights
        $800
        Airfare 4 people x $500 round trip $2,000
        Per Diem 4 people x $50 per day
        x 2 days
        $400
        Total Travel $3,200

      4. Equipment: Identify all tangible, non-expendable personal property to be purchased that has an estimated cost of $5,000 or more per unit and a useful life of more than one year. Details such as the type of equipment, cost, and a brief narrative on the intended use of the equipment for project objectives are required. Each item of equipment must be identified with the corresponding cost. General-purpose equipment (office equipment, etc.) must be justified as to how it will be used on the project. (Property items with a unit cost of less than $5,000 are considered supplies.)

      5. Supplies: “Supplies” means tangible property other than “equipment.” Identify supplies to be used under the project. This may include: software, office supplies, and laboratory supplies such as reagents, chemicals and glassware. Specifically identify computers to be purchased or upgraded.

      6. Contractual: Specify the amount you anticipate expending for services/analyses or consultants and specify the purpose of the contracts and estimated cost. Any procurement of services from individual consultants or commercial firms (including space for workshops) must comply with the competitive procurement requirements of 40 CFR Part 30.40-30.48 or 40 CFR 31.36, as appropriate. Please see Contracts and Subawards for more details.

        Examples of Contractual costs include:

        1. Consultants – Consultants are individuals with specialized skills who are paid at a daily or hourly rate. EPA’s participation in the salary rate (excluding overhead) paid to individual consultants retained by recipients or by a recipient's contractors or subcontractors is limited to the maximum daily rate for a Level IV of the Executive Schedule (formerly GS-18), to be adjusted annually.
        2. Equipment Rental – When there is a need to rent equipment for use on the project, provide information on the type of equipment to be rented, the purpose or use on the project, the length of time needed and the rental rate. Renting or leasing of equipment will require a lease vs. purchase cost analysis prior to approval.
        3. Facility Rental – When it is necessary to rent office or other facilities spaces for project implementation, and the space(s) are located off-site from the organization’s main facility in space not owned by the applicant organization, the cost of the rent may be charged against the award as a contractual expense if the space is used specifically for the project. The budget justifications should provide details on the monthly rental charge and if the rent is pro-rated to the project.
        4. Service or Maintenance Contracts – Costs should be in direct correlation to the use of the equipment for the project (i.e., if a particular machine is used 50% of the time for the project, the project should only be charged 50% of the service/maintenance costs). Provide details of the type of equipment and the amount of the service contract to be paid from EPA funds.
        5. Speaker/Trainer Fees – Information on speakers should include the fee and a description of the services they are providing.
      7. Other: List each item in sufficient detail for the EPA to determine the reasonableness of its cost relative to the research to be undertaken. “Other” items may include publication costs, long distance telephone charges, and photocopying costs. Note that subawards, such as those with other universities for members of the research team, are included in this category. Subawards must have a separate 424A and budget justification, not to exceed one additional page each. Subawards may not be used to acquire services from consultants or commercial firms. Please see Contracts and Subawards for more details.

      8. Indirect Costs: Indirect costs are those incurred by the applicant for a common or joint purpose that benefit more than one cost objective or project, and are not readily assignable to specific cost objectives or projects as a direct cost. In order for indirect costs to be allowable, the applicant must have a negotiated indirect cost rate (e.g., fixed, predetermined, final or provisional), or must have submitted a proposal to their cognizant agency. If indirect costs are included in the budget, identify the cognizant agency and the approved indirect rate. If your organization does not have a cognizant agency, please note that in the budget justification and provide a brief explanation for how you calculated your indirect cost rate.

  13. Resumes

    Provide resumes for each investigator and important co-worker. You may include resumes from staff of subawardees such as universities. Do not include resumes of consultants or other contractors. The resume for each individual must not exceed two consecutively numbered (bottom center), 8.5x11-inch pages of single-spaced, standard 12-point type with 1-inch margins.

  14. Current and Pending Support

    Complete a current and pending support form (provided at Forms and Standard Instructions Download Page) for each investigator and important co-worker. Do not include current and pending support for consultants or other contractors. Include all current and pending research regardless of source.

    Note to all prospective applicants requiring multiple Current and Pending Support Form pages: Due to a limitation in Adobe Acrobat's forms functionality, additional pages cannot be directly inserted into the original PDF form and preserve the form data on the subsequent pages. Multiple page form submissions can be created in Acrobat 8 and later using the "PDF Package" option in the "Create PDF from Multiple Files" function. If you have an earlier version of Adobe Standard or Professional, applicants will need to convert each PDF page of the form to an EPS (Encapsulated Post Script) file before creating the PDF for submission. The following steps will allow applicants with earlier versions of Adobe Standard or Professional to create a PDF package:

    1. Populate the first page of the PDF, and save it as a EPS (Encapsulated Post Script) file.
    2. Reopen the form, and populate it with the data for page 2. Save this page as a different EPS file. Repeat for as many pages as necessary.
    3. Use Acrobat Distiller to convert the EPS files back to PDF.
    4. Open Acrobat Professional, and combine the individual pages into a combined PDF file.
  15. Guidelines, Limitations, and Additional Requirements

    1. Letters of Intent/Letters of Support

      Letters of intent to provide resources for the proposed research or to document intended interactions are limited to one brief paragraph committing the availability of a resource (e.g., use of a person's time or equipment) or intended interaction (e.g., sharing of data, as-needed consultation) that is described in the Research Plan. Letters of intent are to be included as an addition to the budget justification documents. EPA employees are not permitted to provide letters of intent for any application.

      Letters of support do not commit a resource vital to the success of the proposal. A letter of support is written by businesses, organizations, or community members stating their support of the applicant's proposed project. EPA employees are not permitted to provide letters of support for any application.

      Note: Letters of intent or support must be part of the application; letters submitted separately will not be accepted. Any letter of intent or support that exceeds one brief paragraph (excluding letterhead and salutations), is considered part of the individual Research Project Description it is associated with and is included in the 15-page Research Project Description limit for that project. Any transactions between the successful applicant and parties providing letters of intent or support financed with EPA grant funds are subject to the contract and subaward requirements described here Contracts and Subawards.

    2. Funding Opportunity Number (FON)

      At various places in the application, applicants are asked to identify the FON.

      The Funding Opportunity Number for this RFA is:
      ORGANOTYPIC CULTURE MODELS FOR PREDICTIVE TOXICOLOGY CENTER, EPA-G2013-STAR-L1

    3. Confidentiality

      By submitting an application in response to this solicitation, the applicant grants the EPA permission to make limited disclosures of the application to technical reviewers both within and outside the Agency for the express purpose of assisting the Agency with evaluating the application. Information from a pending or unsuccessful application will be kept confidential to the fullest extent allowed under law; information from a successful application may be publicly disclosed to the extent permitted by law.

C. Submission Dates and Times
Applications must be transferred to Grants.gov no later than 11:59:59 pm Eastern Time on the solicitation closing date.  Applications transferred after the closing date and time will be returned to the sender without further consideration.  EPA will not accept any changes to applications after the closing date.

It should be noted that this schedule may be changed without prior notification because of factors not anticipated at the time of announcement.  In the case of a change in the solicitation closing date, a new date will be posted on the NCER web site (Funding Opportunities) and a modification posted on Grants.gov. 

Solicitation Closing Date: January 23, 2014, 11:59:59 pm Eastern Time (applications must be submitted to Grants.gov by this time, see Section IV.E “Submission Instructions and Other Submission Requirements” for further information).

NOTE: Customarily, applicants are notified about evaluation decisions within six months of the solicitation closing date.  Awards are generally made 9-12 months after the solicitation closing date.

D. Funding Restrictions
The funding mechanism for all awards issued under STAR solicitations will consist of assistance agreements from the EPA.  All award decisions are subject to the availability of funds.  In accordance with the Federal Grant and Cooperative Agreement Act, 31 U.S.C. 6301 et seq., the primary purpose of an assistance agreement is to accomplish a public purpose of support or stimulation authorized by federal statute, rather than acquisition for the direct benefit or use of the Agency.  In issuing a grant, the EPA anticipates that there will be no substantial EPA involvement in the design, implementation, or conduct of the research.  However, the EPA will monitor research progress through annual reports provided by grantees and other contacts, including site visits, with the Principal Investigator(s).

If you wish to submit applications for more than one STAR funding opportunity you must ensure that the research proposed in each application is significantly different from any other that has been submitted to the EPA or from any other financial assistance you are currently receiving from the EPA or other federal government agency.

Collaborative applications involving more than one institution must be submitted as a single administrative package from one of the institutions involved.

Each proposed project must be able to be completed within the project period and with the initial award of funds.  Applicants should request the entire amount of money needed to complete the project.  Recipients should not anticipate additional funding beyond the initial award of funds for a specific project.

E. Submission Instructions and Other Submission Requirements
Please read this entire section before attempting an electronic submission through Grants.gov. 

If you do not have the technical capability to utilize the Grants.gov application submission process for this solicitation, send a webmail message at least 15 calendar days before the submission deadline to assure timely receipt of alternate submission instructions.  In your message  provide the funding opportunity number and title of the program, specify that you are requesting alternate submission instructions, and provide a telephone number, fax number, and an email address, if available.  Alternate instructions will be emailed whenever possible.  Any applications submitted through alternate submission methods must comply with all the provisions of this RFA, including Section IV, and be received by the solicitation closing date identified above.

Note:  Grants.gov submission instructions are updated on an as-needed basis.  Please provide your Authorized Organizational Representative (AOR) with a copy of the following instructions to avoid submission delays that may occur from the use of outdated instructions.

  1. Preparing for Submission.  The electronic submission of your application must be made by an official representative of your institution who is registered with Grants.gov and is authorized to sign applications for Federal assistance.  For more information on the registration requirements that must be completed in order to submit an application through grants.gov, go to Grants.gov and click on “Applicants” on the top of the page and then go to the “Get Registered” link on the page. If your organization is not currently registered with Grants.gov, please encourage your office to designate an Authorized Organization Representative (AOR) and ask that individual to begin the registration process as soon as possible. Please note that the registration process also requires that your organization have a DUNS number and a current registration with the System for Award Management (SAM) and the process of obtaining both could take a month or more.  Applicants must ensure that all registration requirements are met in order to apply for this opportunity through grants.gov and should ensure that all such requirements have been met well in advance of the submission deadline.  Registration on grants.gov, SAM.gov, and DUNS number assignment is FREE.

    To begin the application process under this grant announcement, go to Grants.gov and click on “Applicants” on the top of the page and then “Apply for Grants” from the dropdown menu and then follow the instructions accordingly. Please note: To apply through grants.gov, you must use Adobe Reader software and download the compatible Adobe Reader version. For more information about Adobe Reader, to verify compatibility, or to download the free software, please visit Grants.gov Adobe Reader Compatibility.

    You may also be able to access the application package for this announcement by searching for the opportunity on Grants.gov.   Go to Grants.gov and then click on “Search Grants” at the top of the page and enter the Funding Opportunity Number, EPA-G201X-STAR-XX, or the CFDA number that applies to the announcement (CFDA 66.509), in the appropriate field and click the Search button.  Alternatively, you may be able to access the application package by clicking on the Application Package button at the top right of the synopsis page for the announcement on Grants.gov.  To find the synopsis page, go to Grants.gov and click “Browse Agencies” in the middle of the page and then go to “Environmental Protection Agency” to find the EPA funding opportunities.

  2. Acknowledgement of Receipt.  The complete application must be transferred to Grants.gov no later than 11:59:59 pm Eastern Time on the solicitation closing date (see “Submission Dates and Times”).  Applications submitted through grants.gov will be time and date stamped electronically. Grants.gov provides an on-screen notification of successful initial transfer as well as an email notification of successful transfer from Grants.gov to EPA.  While it is advisable to retain copies of these Grants.gov acknowledgements to document submission, the only official documentation that the application has been received by NCER is the email acknowledgement sent by NCER to the Lead/Contact PI and the Administrative Contact.  This email will be sent from receipt.application@epa.gov; emails to this address will not be accepted.  If an email acknowledgment from receipt.application@epa.gov has not been received within 30 days of the solicitation closing date, immediately inform the Eligibility Contact shown in this solicitation.  Failure to do so may result in your application not being reviewed.

  3. Application Package Preparation.  Your organization’s AOR must submit your complete application package electronically to EPA through Grants.gov (Grants.gov) no later than January 23, 2014, 11:59:59 pm Eastern Time.   Please allow for enough time to successfully submit your application process and allow for unexpected errors that may require you to resubmit.    

    Please submit all of the application materials described below using the grants.gov application package that you downloaded using the instructions above. For additional instructions on completing and submitting the electronic application package, click on the “Show Instructions” tab that is accessible within the application package itself. 

    The application package consists of the following mandatory documents. 

    1. Application for Federal Assistance (SF 424):  Complete the form except for the “competition ID” field.
    2. EPA Key Contacts Form 5700-54:  Complete the form.  If additional pages are needed, see (d) below.
    3. SF-424A Budget Information for Non-Construction Programs: Only complete “Section B-Budget Categories”.   Provide the object class budget category (a. - k.) amounts for each budget year under the “Grant Program, Function or Activity” heading.  Each column reflects a separate budget year. Provide one SF-424A for the total Center budget and separate SF-424As for each research project as well as for the administrative unit.  Additional SF-424As may be downloaded at Forms and Standard Instructions Download Page.  Attach the additional SF-424As to the Project Narrative.
    4. Project Narrative Attachment Form (click on “Add Mandatory Project Narrative”):  Attach a single electronic PDF file labeled “Application” that contains the items described in Section IV.B.3. through IV.B.15.a (Table of Contents, Abstracts, Center Description, Research Plan Description(s), Quality Management Plan, Human Subjects Research Statement, Data Plan, Administrative Unit Description, References, Additional SF-424As for the individual research projects and administrative unit, Budget Justifications for the individual research projects and administrative unit, Resumes, Current and Pending Support, and Letters of Intent/Support) of this solicitation.  In order to maintain format integrity, this file must be submitted in Adobe Acrobat PDF.  Please review the PDF file for conversion errors prior to including it in the electronic application package; requests to rectify conversion errors will not be accepted if made after the solicitation closing date and time. If Key Contacts Continuation pages (see Forms and Standard Instructions Download Page) are needed, place them before the Table of Contents (Section IV.B.3.).

    Please note that applicants are limited to using the following characters in all attachment file names.  Valid file names may only include the following UTF-8 characters: 
    A-Z, a-z, 0-9, underscore ( _ ), hyphen (-), space, period. If applicants use any other characters when naming their attachment files their applications will be rejected by grants.gov.

    Once the application package has been completed, the “Submit” button should be enabled.  If the “Submit” button is not active, please call Grants.gov for assistance at 1-800-518-4726.  Applicants who are outside the U.S. at the time of submittal and are not able to access the toll-free number may reach a Grants.gov representative by calling 606-545-5035.  Investigators should save the completed application package with two different file names before providing it to the AOR to avoid having to re-create the package should submission problems be experienced or a revised application needs to be submitted.  Note:  Revised applications must be submitted before the solicitation closing date and time.

  4. Submitting the application.  The application package must be transferred to Grants.gov by an AOR.  The AOR should close all other software before attempting to submit the application package.  Click the “submit” button of the application package. Your Internet browser will launch and a sign-in page will appear.  Note:  Minor problems are not uncommon with transfers to Grants.gov.  It is essential to allow sufficient time to ensure that your application is submitted to Grants.gov BEFORE 11:59:59 pm Eastern Time on the solicitation closing date.  The Grants.gov support desk operates 24 hours a day, seven days a week, except Federal Holidays.

    A successful transfer will end with an on-screen acknowledgement.  For documentation purposes, print or screen capture this acknowledgement.  If a submission problem occurs, reboot the computer – turning the power off may be necessary – and re-attempt the submission. 

    Note:  Grants.gov issues a “case number” upon a request for assistance.

  5. Transmission Difficulties.  If transmission difficulties that result in a late transmission, no transmission, or rejection of the transmitted application are experienced, and following the above instructions do not resolve the problem so that the application is submitted to Grants.Gov by the deadline date and time, follow the guidance below.  The Agency will make a decision concerning each late submission on a case-by-case basis as to whether it should be forwarded for peer review.  All emails, as described below, are to be sent to peterson.todd@epa.gov with the FON in the subject line.

    Please note that if the application you are submitting is greater than 70 MB in size, please call or send an email message to the Electronic Submissions Contact listed for this RFA.  The Agency may experience technical difficulty downloading files of this size from Grants.gov.  Therefore, it is important that the Agency verify that the file can be downloaded.  The Agency will provide alternate submission instructions if the file cannot be downloaded.

    1. If you are experiencing problems resulting in an inability to upload the application to Grants.gov, it is essential to call Grants.gov for assistance at 1-800-518-4726 before the application deadline.  Applicants who are outside the U.S. at the time of submittal and are not able to access the toll-free number may reach a Grants.gov representative by calling 606-545-5035.  Be sure to obtain a case number from Grants.gov.
    2. Unsuccessful transfer of the application package: If a successful transfer of the application cannot be accomplished even with assistance from Grants.gov due to electronic submission issues, send an email message by 11:59:59 pm Eastern Time on the solicitation closing date. The email message must document the problem and include the Grants.gov case number as well as the entire application in PDF format as an attachment.
    3. Grants.gov rejection of the application package:  If a notification is received from Grants.gov stating that the application has been rejected for reasons other than late submittal, promptly send an email to Todd Peterson (peterson.todd@epa.gov) with the FON in the subject line within one business day of the closing date of this solicitation.  The email should include any materials provided by Grants.gov and attach the entire application in PDF format.

V. APPLICATION REVIEW INFORMATION

A. Peer Review
All eligible grant applications are reviewed by appropriate external technical peer reviewers   based on the criteria and process described below.  This review is designed to evaluate each application according to its scientific merit.  The individual external peer reviewers include non-EPA scientists, engineers, social scientists, and/or economists who are accomplished in their respective disciplines and proficient in the technical subjects they are reviewing.

Prior to the external technical peer review panel meeting, all reviewers will receive electronic copies of all applications, as well as a full set of abstracts for the applications. Each application will be assigned to a minimum of three primary peer reviewers, one of whom will be assigned the role of Rapporteur. Each reviewer will be assigned up to approximately 10 applications on which to serve as a primary reviewer. During the review period leading up to the panel meeting, primary reviewers will read the full set of abstracts and entire application package for each application they are assigned. They will also prepare a written individual evaluation for each assigned application that addresses the peer review criteria described below and rate the application with a score of excellent, very good, good, fair, or poor. 

At the beginning of the panel meeting, each primary reviewer will report their ratings for the applications they reviewed.  Those applications receiving at least two ratings of Very Good or one rating of Excellent from among the primary reviewers will then be further discussed by the panel in terms of the peer review criteria below.  In addition, if there is one Very Good rating among the primary reviewers of an application, the primary reviewer, whose initial rating is the Very Good, may request discussion of the application by the peer review panel.  All other applications will be declined for further consideration.

After the discussion of an application by the panel, the primary reviewers may revise their initial ratings and if they do so, this will also be documented. The final ratings of the primary reviewers will then be translated by EPA into the final peer review score (excellent, very good, good, fair, or poor) for the application. This is reflected in a peer review results document developed by the Rapporteur which combines the individual initial and final evaluations of the primary reviewers and captures any substantive comments from the panel discussion. This score will be used to determine which applications undergo the internal programmatic review discussed below.  A peer review results document is also developed for applications that are not discussed.  However, this document is a consolidation of the individual primary reviewer initial evaluations, with an average of the scores assigned by the primary reviewers.  

Peer reviewers consider an application’s merit based on the criteria below.  Criteria 1-6 are listed in descending order of importance:

  1. Research Proposal

    Reviewers will evaluate each proposed research project included in the Center based on the criteria below (criteria 1.a – 1.h are of equal importance).

    1. The originality and creativity of the proposed research, and the appropriateness and adequacy of the proposed research methods including quality assurance/quality control protocols.
    2. Practical and technically defensible approach that can be performed within the proposed time period.
    3. Research contributes to scientific knowledge in the topic area and supports trans-diciplinarity.
    4. The proposed research challenges and seeks to shift current research, design, or engineering paradigms by using innovative theoretical concepts, approaches or methodologies, instrumentation or interventions.
    5. Projected benefits of the proposed activity to the environment, economy and society, including human health.
    6. Partners in the proposed project(s) contribute significant benefits to achieving the overall purpose and objectives of the research.
    7. The results are disseminated broadly to enhance scientific and technological understanding.
    8. The proposal is well prepared with supportive information that is self-explanatory or understandable.
  2. Overall Center

    Applications will be evaluated based on the quality and extent to which the overall Center addresses the following criteria (criteria 2.a-2.d are equal in importance).

    1. Interdisciplinary nature and relevance of the proposed activities, integration of the projects around an overarching theme, and development of research projects which reflect the Center’s commitment to achieving its research goals.
    2. Capacity of the research projects collectively to result in a greater contribution to the overall goals of the Center than if each were pursued independently.
    3. Qualifications of the Principal Investigator(s) and other key personnel, including research training, demonstrated knowledge of pertinent literature, experience, publication records and experience. Complementary experience and capabilities should be clearly identified for each participant or cooperator. All key personnel must make a significant time commitment to the project.
    4. The number, capabilities, and relevance of partners and collaborating organizations.
  3. Administrative Unit (criteria 3.a – 3.d are equal in importance)

    1. Scientific and organizational structure of the Center. Are the lines of authority and administrative structure designed for effective management? How does the administrative structure maximize the Center's capability to take advantage of research opportunities?
    2. The effectiveness of leaders, specifically as managers of the Center. Has the Center Director demonstrated the capacity to ensure quality control and possesses the experience to effectively administer and integrate all components of the Center? Is the percent of effort committed to the management of the Center appropriate?
    3. Duties and percent efforts of administrative staff of the Center and their qualifications and contributions to the specialized needs and conduct of the Center’s research activities.
    4. Effectiveness of the Center's internal planning, technology transfer, and quality management plan. Is the plan for tracking and monitoring progress toward achieving expected results (outputs and outcomes) adequate?  Is the approach for ensuring successful achievement of project objectives adequate and in accordance with the Center’s project schedule and milestones?  Is the approach, procedures, and controls for ensuring timely and efficient expenditure of awarded grant funds well defined and acceptable?
  4. Responsiveness: The responsiveness of the proposal to the research needs identified for the research area.  The proposal adequately addresses the objectives and special considerations specified by the RFA.

  5. Facilities and equipment: The availability and/or adequacy of the facilities and equipment proposed for the project.  Note any deficiencies that may interfere with the successful completion of the research.

  6. Budget: Although budget information does not reflect on the application’s scientific merit, the reviewers are asked to provide their view on the appropriateness and/or adequacy of the proposed budget and its implications for the potential success of the proposed research.  Input on requested equipment is of particular interest.

B. Programmatic Review
Applications receiving final peer review scores of excellent or very good will then undergo an internal programmatic review, as described below, conducted by technical experts from the EPA, including individuals from the Office of Research and Development (ORD) and program and regional offices involved with the science or engineering proposed.  All other applications are automatically declined.

Applicants who received final scores of excellent or very good as a result of the peer review process will be asked to provide additional information for the programmatic review pertaining to the proposed Lead PI’s (in the case of Multiple-PI applications, the Contact PI’s) "Past Performance and Reporting History."  The applicant must provide the EPA Project Officer with information on the proposed Lead/Contact PI's past performance and reporting history under prior Federal agency assistance agreements (assistance agreements include grants and cooperative agreements but not contracts) in terms of: (i) the level of success in managing and completing each agreement, and (ii) history of meeting the reporting requirements under each agreement.

This information is required only for the proposed Lead/Contact PI's performance under Federal assistance agreements initiated within the last three years that were similar in size and scope to the proposed project. 

The specific information required for each agreement is shown below, and must be provided within three weeks of EPA's request.  A maximum of three pages will be permitted for the response; excess pages will not be reviewed.  Note: If no prior past performance information and/or reporting history exists, you will be asked to so state.

  1. Name of Granting Agency.
  2. Grant/Cooperative agreement number.
  3. Grant/Cooperative agreement title.
  4. Brief description of the grant/cooperative agreement.
  5. A description of how the agreement is similar in size and scope to the proposed project and whether or not it was successfully managed and completed; if not successfully managed and completed, provide an explanation.
  6. Information relating to the proposed Lead/Contact PI's past performance in reporting on progress towards achieving the expected results (outputs/outcomes) under the agreement.  Include the history of submitting timely progress/final technical reports, describe how progress towards achieving the expected results was reported/documented, and if such progress was not being made, provide an explanation of whether, and how, this was reported. 
  7. Total (all years) grant/cooperative agreement dollar value.
  8. Project period.
  9. Technical contact (project officer), telephone number, and Email address (if available).

The purpose of the programmatic review is to ensure an integrated research portfolio for the Agency and help determine which applications to recommend for award.  In conducting the programmatic review, the EPA will consider information provided by the applicant and may consider information from other sources, including prior and current grantors and agency files.

The internal programmatic review panel will assess (relevance is more important than the Lead/Contact PI's past performance):

  1. The relevance of the proposed science to EPA research priorities.
  2. The proposed Lead/Contact PI's past performance under Federal agency assistance agreements (assistance agreements include grants and cooperative agreements but not contracts) initiated within the last three years that were similar in size and scope to the proposed project in two areas:  First, in successfully managing and completing these prior Federal assistance projects, including whether there is a satisfactory explanation for any lack of success.  Second, in reporting progress toward achieving results (outputs/outcomes) under these agreements, including the proposed Lead/Contact PI's history of submitting timely progress/final technical reports that adequately describe the progress toward achieving the expected results under the agreements.  Any explanation of why progress toward achieving the results was not made will also be considered.  Applicants whose proposed Lead PI/Contact PI has no relevant past performance and/or reporting history, or for whom this information is not available, will be evaluated neither favorably nor unfavorably on these elements.

C. Human Subjects Research Statement (HSRS) Review
Applications being considered for funding after the Programmatic Review that involve human subjects research studies will have their HSRS reviewed by EPA’s HSRRO prior to award. The HSRRO will review the information provided in the HSRS and the Research Plan to determine if the ethical treatment of human subjects is described in a manner appropriate for conditional approval to be granted.

D. Funding Decisions
Final funding decisions are made by the NCER Director based on the results of the peer review and the internal programmatic review and, where applicable, the EPA HSRRO’s assessment of the applicant’s HSRS (see Section IV.B.8). In addition, in making the final funding decisions, the NCER Director may also consider program balance and available funds. Applicants selected for funding will be required to provide additional information listed below under “Award Notices.” The application will then be forwarded to EPA’s Grants and Interagency Agreement Management Division for award in accordance with the EPA’s procedures.

VI. AWARD ADMINISTRATION INFORMATION

A. Award Notices
Customarily, applicants are notified about evaluation decisions within six months of the solicitation closing date.  A Peer Review Results document summarizing the scientific review  will be provided to each applicant with an award or declination letter. 

Applicants to be recommended for funding will be required to submit additional certifications and an electronic version of the revised project abstract.  They may also be asked to provide responses to comments or suggestions offered by the peer reviewers and/or submit a revised budget.  EPA Project Officers will contact the Lead PI/Contact PI to obtain these materials.  Before or after an award, applicants may be required to provide additional quality assurance documentation.

The official notification of an award will be made by the Agency’s Grants and Interagency Agreement Management Division.  Applicants are cautioned that only a grants officer is authorized to bind the Government to the expenditure of funds; preliminary selection by the NCER Director in the Office of Research and Development does not guarantee an award will be made.  For example, statutory authorization, funding, or other issues discovered during the award process may affect the ability of EPA to make an award to an applicant.  The award notice, signed by an EPA grants officer, is the authorizing document and will be provided through electronic or postal mail.

B. Disputes
Disputes related to this assistance agreement competition will be resolved in accordance with the dispute resolution procedures set forth in 70 FR 3629, 3630 (January 26, 2005) which can be found at Dispute Resolution Procedures .  Questions regarding disputes may be referred to the Eligibility Contact identified below.

C. Administrative and National Policy Requirements
Additional provisions that apply to this solicitation and/or awards made under this solicitation, including but not limited to those related to DUNS, SAM, copyrights, disputes, and administrative capability, can be found at Fiscal Year 2010 Competitive Grant Awards

These, and the other provisions that can be found at the website link, are important, and applicants must review them when preparing applications for this solicitation.  If you are unable to access these provisions electronically at the website above, please communicate with the EPA contact listed in this solicitation to obtain the provisions.

Expectations and responsibilities of NCER grantees and cooperative agreement holders are summarized in this section, although the terms grant and grantee are used.  See Guidance & Frequent Questions for the full terms and conditions associated with an award, including which activities require prior approval from the EPA.

  1. Meetings: Principal Investigators will be expected to budget for, and participate in, All-Investigators Meetings (also known as progress reviews) approximately once per year with EPA scientists and other grantees to report on research activities and discuss issues of mutual interest.

  2. Approval of Changes after Award: Prior written approval of changes may be required from EPA. Examples of these changes are contained in 40 C.F.R. 30.25.  Note: prior written approval is also required from the EPA Award Official for incurring costs more than 90 calendar days prior to award.

  3. Human Subjects: A grant applicant must agree to meet all EPA requirements for studies using human subjects prior to implementing any work with these subjects.  These requirements are given in 40 CFR Part 26.  Studies involving intentional exposure of human subjects who are children or pregnant or nursing women are prohibited by Subpart B of 40 CFR Part 26.  For observational studies involving children or pregnant women and fetuses please refer to Subparts C & D of 40 CFR Part 26.  U.S. Department of Health and Human Services regulations at 45 CFR Part 46.101(e) have long required "... compliance with pertinent Federal laws or regulations which provide additional protection for human subjects."  EPA’s regulation 40 CFR Part 26 is such a pertinent Federal regulation.  Therefore, the applicant's Institutional Review Board (IRB) approval must state that the applicant's study meets the EPA's regulations at 40 CFR Part 26.  No work involving human subjects, including recruiting, may be initiated before the EPA has received a copy of the applicant’s IRB approval of the project and the EPA has also provided approval.  Where human subjects are involved in the research, the recipient must provide evidence of subsequent IRB reviews, including amendments or minor changes of protocol, as part of annual reports.

    Guidance and training for investigators conducting EPA-funded research involving human subjects may be obtained here:
    Ethics, Regulations, and Policies
    Human Subjects Research at the Environmental Protection Agency: Ethical Standards and Regulatory Requirements

  4. Data Access and Information Release: After award, all data first produced under the award must be made available to the NCER Project Officer without restriction and be accompanied by comprehensive metadata documentation adequate for specialists and non-specialists alike to be able to understand how and where the data were obtained and to evaluate the quality of the data.  If requested, the data products and their metadata must be provided to the NCER Project Officer in a standard exchange format no later than the due date of the grant's final report or the publication of the data product's associated results, whichever comes first.

    Congress, through OMB, has instructed each federal agency to implement Information Quality Guidelines designed to "provide policy and procedural guidance...for ensuring and maximizing the quality, objectivity, utility, and integrity of information, including statistical information, disseminated by Federal agencies." The EPA's implementation may be found at EPA Information Quality Guidelines (EPA IQG).  These procedures may apply to data generated by grant recipients if those data are disseminated as described in the Guidelines.

  5. Reporting: 

    A grant recipient must agree to provide annual progress reports, with associated summaries, and a final report with an executive summary.  The summaries will be posted on NCER’s website.

    A grant recipient must agree to provide copies of any peer reviewed journal article(s) resulting from the research during the project period.  In addition, the recipient should notify the NCER Project Officer of any papers published after completion of the grant that were based on research supported by the grant.  NCER posts references to all publications resulting from a grant on the NCER web site.

  6. Acknowledgement of EPA Support: EPA’s full or partial support must be acknowledged in journal articles, oral or poster presentations, news releases, interviews with reporters and other communications.  Any documents developed under this agreement that are intended for distribution to the public or inclusion in a scientific, technical, or other journal shall include the following statement:

    This publication [article] was developed under Assistance Agreement No.________ awarded by the U.S. Environmental Protection Agency to [name of recipient].  It has not been formally reviewed by EPA.  The views expressed in this document are solely those of [name of recipient or names of authors] and do not necessarily reflect those of the Agency.  EPA does not endorse any products or commercial services mentioned in this publication.

    A graphic that may be converted to a slide or used in other ways, such as on a poster, is located at Guidance & Frequent Questions.  EPA expects recipients to use this graphic in oral and poster presentations.

  7. Coordination after Grant Award:  Science Advisory Committee (SAC) - After award, the Center must establish a SAC. The SAC membership will typically consist of peers selected from the academic, private, non-profit, and public sectors.  The function of the SAC is to assist in evaluating the (1) merit, value and contribution of the Center’s projects, and (2) relevance and importance of the individual research elements to accomplishing the overall goals of the Center.  Within 90 days of the award, the Principal Investigator must submit a list of nominees for the SAC to the Project Officer. Potential SAC members must NOT be contacted, identified, or queried prior to receipt of the award.

VII. AGENCY CONTACTS

Further information, if needed, may be obtained from the EPA contacts indicated below. Information regarding this RFA obtained from sources other than these Agency Contacts may not be accurate. Email inquiries are preferred.

Eligibility Contact: Ron Josephson (josephson.ron@epa.gov); phone: 703-308-0442
Electronic Submissions: Todd Peterson (peterson.todd@epa.gov); phone: 703-308-7224
Technical Contact: Barbara Klieforth (klieforth.barbara@epa.gov); phone: 703-347-8044

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