FY20 CSS Biotechnology Full RFA 5 6 20 (2).pdf

COVID-19 Update: EPA is providing flexibilities to applicants experiencing challenges related to COVID-19. Please see the Flexibilities Available to Organizations Impacted by COVID-19 clause in Section IV of EPA’s Solicitation Clauses.

OVERVIEW INFORMATION

U.S. Environmental Protection Agency Office of Science Advisor, Policy and Engagement Office of Research and Development Science to Achieve Results (STAR) Program

ASSESSMENT TOOLS FOR BIOTECHNOLOGY

PRODUCTS

This is the initial announcement of this funding opportunity.

Funding Opportunity Number: EPA-G2020-STAR-C1, Assessment Tools for Biotechnology Products Funding Opportunity Number: EPA-G2020-STAR-C2, Early Career: Assessment Tools for Biotechnology Products

Catalog of Federal Domestic Assistance (CFDA) Number: 66.509

Solicitation Opening Date: May 6, 2020 Solicitation Closing Date: July 15, 2020:11:59:59 pm Eastern Time

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 https://www.epa.gov/grants/epa-solicitation-clauses

B. Cost Sharing C. Other

IV. APPLICATION AND SUBMISSION INFORMATION

A. Grants.gov Submittal Requirements and Limited Exception Procedures B. Application Package Information C. Content and Form of Application Submission D. Submission Dates and Times E. Funding Restrictions F. Submission Instructions and Other Submission Requirements

V. APPLICATION REVIEW INFORMATION

A. Peer Review B. Relevancy Review C. Past Performance History Review D. Human Subjects Research Statement (HSRS) Review E. Evaluation of the Scientific Data Management Plan F. Funding Decisions G. Additional Provisions for Applicants Incorporated into the Solicitation

VI. AWARD ADMINISTRATION INFORMATION

A. Award Notices B. Disputes C. Administrative and National Policy Requirements

VII. AGENCY CONTACTS

Access Standard STAR Forms (https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms) View research awarded under previous solicitations (https://www.epa.gov/research-grants/research-grant-areas)

SUMMARY OF PROGRAM REQUIREMENTS

Synopsis of Program:

The United States Environmental Protection Agency (EPA), as part of its Science to Achieve Results (STAR) program, is seeking applications proposing research to support the development of improved science-based human health and environmental risk assessments of new biotechnology products, including those developed through synthetic biology, genome editing, and metabolic engineering.

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 https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms https://www.epa.gov/research-grants/research-grant-areas https://www.epa.gov/research-grants/research-grant-areas applications must include a Human Subjects Research Statement (HSRS, as described in Section IV.C.6.c of this solicitation), 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.D and V.F of this solicitation.

Guidance and training for investigators conducting EPA-funded research involving human subjects may be obtained here:

https://www.epa.gov/osa/basic-information-about-human-subjects-research-0 https://www.ecfr.gov/cgi-bin/text-idx?tpl=/ecfrbrowse/Title40/40cfr26_main_02.tpl

The STAR Program’s goal is to stimulate and support scientific and engineering research that advances EPA’s mission to protect human health and the environment. It is a competitive, peer-reviewed, extramural research program that provides access to the nation’s best scientists and engineers in academic and other nonprofit research institutions. STAR funds research on the environmental and public health effects of air quality, environmental changes, water quality and quantity, hazardous waste, toxic substances, and pesticides.

In addition to regular awards, this solicitation includes the opportunity for early career awards.

The purpose of the early career award is to fund research projects smaller in scope and budget by early career PIs. It is expected that the majority of the research will be performed by early career investigators. Further, it is expected that significant resources will be allotted to early career investigators to perform the research. Please see Section III of this Request for Applications (RFA) for details on the early career eligibility criteria.

Award Information:

Anticipated Type of Award: Grant Estimated Number of Awards: Approximately 7 awards, 4 regular and 3 early career awards Anticipated Funding Amount: Approximately $4.4 million total for all awards Potential Funding per Award: Up to a total of $760,000 for regular awards, and up to a total of $453,333 for early career awards, including direct and indirect costs, with a maximum duration of 3 years. Cost-sharing is not required. Applications with budgets exceeding the total award limits will not be considered.

Eligibility Information:

Public and private nonprofit institutions/organizations, public and 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. Special eligibility criteria apply to the early career award portion of this RFA. 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.F. “Submission Instructions and other Submission Requirements”). Note: With the exception of the current and pending support form (available at https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-https://www.epa.gov/osa/basic-information-about-human-subjects-research-0 https://www.ecfr.gov/cgi-bin/text-idx?tpl=/ecfrbrowse/Title40/40cfr26_main_02.tpl https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms forms), all necessary forms are included in the electronic application package. Make sure to include the current and pending support form in your Grants.gov submission.

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 unique entity identifier (e.g., ‘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, see Section IV.A below for additional guidance and instructions.

Agency Contacts:

Technical Contact: Barbara Klieforth; phone: 202-564-7723; email: klieforth.barbara@epa.gov Eligibility Contact: Ron Josephson; phone: 202-564-7823; email: josephson.ron@epa.gov Electronic Submissions Contact: Debra M. Jones; phone: 202-564-7839; email:

jones.debram@epa.gov

I. FUNDING OPPORTUNITY DESCRIPTION

A. Introduction

Research solicited in this RFA will support the development of improved science-based human health and environmental risk assessments of novel biotechnology products. Recent advances in synthetic biology methods can be used to create substances and life forms not found in nature, which may in turn be used to make biotechnology products. Oversight of biotechnology products is shared between the EPA, the U.S. Department of Agriculture (USDA), and the U.S. Food and Drug Administration (FDA). Research solicited in this RFA will support the development of improved science-based human health and environmental risk assessments of novel synthetic biology products. For the purposes of this RFA, biotechnology products of interest include:

industrial or consumer chemicals; pesticides (including pesticide intermediates); and new microbes used in biomass conversion for chemical production, microbial fuel cells, mining and resource extraction, building materials, waste remediation and pollution control, and non-pesticidal agriculture applications (e.g., biofertilizers, weather and climate modification). Robust and efficient evaluation and monitoring tools are needed to ensure these biotechnology products’ safety and to assure public trust (Morton et al., 2019). Some examples of appropriate risk assessment tools include models, bioinformatic systems, and field-based and in vitro methods (SCENIHR, 2015). This research will help inform high-priority research areas identified by the EPA Office of Research and Development (ORD) and included in the Chemical Safety for Sustainability (CSS) National Research Program. The EPA currently supports CSS-related research grants resulting from previous solicitations. Information regarding current research can be found on EPA’s Research Grants website at https://www.epa.gov/research-grants/.

https://www.epa.gov/research-grants/research-funding-opportunities-how-apply-and-required-forms mailto:klieforth.barbara@epa.gov mailto:josephson.ron@epa.gov mailto:jones.debram@epa.gov https://www.epa.gov/aboutepa/about-chemical-safety-sustainability-research-program https://www.epa.gov/aboutepa/about-chemical-safety-sustainability-research-program https://www.epa.gov/research-grants/

In addition to regular awards, this solicitation includes the opportunity for early career awards.

The purpose of the early career award is to fund research projects smaller in scope and budget by early career PIs. Please see Section III of this RFA for details on the early career eligibility criteria.

EPA recognizes that it is important to engage all available minds to address the environmental challenges the Nation faces. At the same time, EPA seeks to expand the environmental conversation by including members of communities which may have not previously participated in such dialogues to participate in EPA programs. For this reason, EPA strongly encourages all eligible applicants identified in Section III, including minority serving institutions (MSIs), to apply under this opportunity.

For purposes of this solicitation, the following are considered MSIs:

1. Historically Black Colleges and Universities, as defined by the Higher Education Act (20 U.S.C. § 1061). A list of these schools can be found at Historically Black Colleges and Universities;

2. Tribal Colleges and Universities (TCUs), as defined by the Higher Education Act (20 U.S.C. § 1059c(b)(3) and (d)(1)). A list of these schools can be found at American Indian Tribally Controlled Colleges and Universities;

3. Hispanic-Serving Institutions (HSIs), as defined by the Higher Education Act (20 U.S.C. § 1101a(a)(5)). A list of these schools can be found at Hispanic-Serving Institutions;

4. Asian American and Native American Pacific Islander-Serving Institutions; (AANAPISIs), as defined by the Higher Education Act (20 U.S.C. § 1059g(a)(2)). A list of these schools can be found at Asian American and Native American Pacific Islander-Serving Institutions; and

5. Predominately Black Institutions (PBIs), as defined by the Higher Education Act of 2008, 20 U.S.C. 1059e(b)(6). A list of these schools can be found at Predominately Black Institutions.

B. Background

Synthetic biology, genome editing, and metabolic engineering, along with a wide range of other transformational tools and techniques, are enabling the development of entirely new generations of synthetic biology (referred to as “synbio” in this RFA) biotechnology products (NAS, 2017).

For the purposes of this RFA, synthetic biology is defined as an interdisciplinary area that applies bioengineering tools to biology in order to fabricate a wide range of biotechnology products. Research solicited in this RFA will support the development of improved science-based human health and environmental risk assessments of novel synthetic biology products.

Information and effective tools are needed to evaluate and monitor parameters such as long-term stability, persistence, efficacy, and reliability of synthetic biology products in order to assess any potential unintended human and ecological impacts (U.S.A.C.E., 2019). Better understanding of how synthetic biology products interact at both the cellular and systems levels will allow for https://sites.ed.gov/whhbcu/one-hundred-and-five-historically-black-colleges-and-universities/ https://sites.ed.gov/whhbcu/one-hundred-and-five-historically-black-colleges-and-universities/ https://sites.ed.gov/whiaiane/tribes-tcus/tribal-colleges-and-universities/ https://sites.ed.gov/whiaiane/tribes-tcus/tribal-colleges-and-universities/ https://www2.ed.gov/about/offices/list/ope/idues/hsi-eligibles-2016.pdf https://www.google.com/maps/d/viewer?mid=1XVkOWKMDORm53pvU0L8EPsrJC94&msa=0&ie=UTF8&t=m&z=3&source=embed&ll=40.58644586187277%2C-148.28228249999984 https://www.google.com/maps/d/viewer?mid=1wlIi3j7gtlNq_w-0NKAb2bF2VmY&ie=UTF&msa=0&ll=37.35160769312532%2C-96.17229800000001&z=4 informed decisions on the safety and efficacy of novel products of biotechnology, now increasingly available for industrial and commercial applications (NAS, 2017).

To realize the potential benefits of synthetic biology while avoiding unintended consequences that may adversely impact public health and the environment, it is crucial to better comprehend the underpinning science and to develop appropriate assessment technologies. (Gronvall, 2017;

U.S.A.C.E., 2019; NAS, 2017). Innovative risk assessment tools are needed to evaluate these new products (NAS, 2017). The manufacturing, agricultural, and biomedical benefits of these varied products will depend on robust evaluation approaches and monitoring capabilities to ensure their safety and to assure public trust (Jones et al., 2019; Trump et al., 2018; U.S.E.P.A., 2017; Gronvall, 2017).

One rapidly expanding application area of biotechnology is modification of the genetic makeup of plants, animals, and microbes, which themselves then become valuable products (CRS, 2019).

Traditional breeding and selection techniques, or early methods of genetic engineering, have been surpassed by developments in synthetic biology that have enabled unprecedented advances in the number and types of products being developed. Novel new techniques, such as CRISPR- Cas9 (CRS, 2018) and other genome engineering technologies, have transformed and accelerated the creation and production of the next generation (EBRC, 2019) of agricultural (e.g., genetically engineered products that qualify as pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act-FIFRA), medical, and industrial materials (e.g., microbial biotechnology-derived substances are considered new chemicals under the Toxic Substances Control Act- TSCA). United States law mandates that risk assessment of a product is based on its end use, including biotechnology products (U.S. EPA, 2019 and 2017).

For the purposes of this RFA: synbio organisms are whole organisms that have been engineered using synthetic biology; synbio components are synthetic biology constructs that may be used or deployed outside of a living organism; synthetic biology constructs and by-products are new or redesigned biological entities or novel biomolecules not derived from extant organisms (e.g., enzymes, genetic circuits, atypical nucleotides, noncanonical amino acids, and cells);

biocontainment methodologies prevent unintended proliferation of genetically modified organisms in the environment; and genetic restriction technologies are methods that impede transgene movement. Additionally, “synthetic genetic constructs” are defined as new biological entities, not directly derived from extant organisms, such as enzymes, genetic circuits, and cells or the redesign of existing biological systems for useful purposes. “Genetic restriction technologies” are defined as methods that impede transgene movement.

Novel synthetic biology products present new challenges to the assessment of potential human health and environmental risk. For example, risk assessment efforts currently rely largely on existing databases of known substances, but new products have no such data. Empirical and modeling research efforts will help inform risk assessments of emerging biotechnology products, especially where comparisons to previously developed products are limited (U.S. EPA, 2017).

This RFA solicits research to inform development of assessment tools to better understand the characteristics and interactions of synbio organisms, components, and their biocontainment strategies, and to characterize potential risks to human health and the environment.

For synthetically engineered organisms and components, there are 4 general questions that must be addressed regarding risk assessment:

1. Is there a hazard? (Hazard identification);

2. How likely is the hazard to occur? (Quantifying the probability of occurrence;

identifying likely hazard exposure scenarios);

3. What is the severity of hazard resulting from specific levels of exposure? (Quantifying effects)

4. Is there an effect above and beyond what might occur with a native, unmodified organism, or one with similar traits which was developed using older, more established, technologies?

C. Authority and Regulations

The authority for this RFA and resulting awards is contained in the Toxic Substances Control Act, 15 U.S.C. 2609, Section 10, as amended by P.L. 106-74 and the Federal Insecticide, Fungicide, and Rodenticide Act, 7 U.S.C. 136r, Section 20, as amended by P.L. 106-74.

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. Further note applications dealing with any aspect of or related to hydraulic fracking will not be funded by EPA through this program.

Additional applicable regulations include: 2 CFR Part 200, 2 CFR Part 1500, and 40 CFR Part 40 (Research and Demonstration Grants).

D. Specific Areas of Interest/Expected Outputs and Outcomes Note to applicant: The term “output” means an environmental activity, effort, and/or associated work products related to an environmental goal or objective, that will be produced or provided over a period of time or by a specified date. The term “outcome” means the result, effect or consequence that will occur from carrying out an environmental program or activity that is related to an environmental or programmatic goal or objective.

The activities to be funded under this announcement support EPA’s FY 2018-22 Strategic Plan (https://www.epa.gov/planandbudget/strategicplan.html). Activities to be funded under this announcement support Goal 3: Greater Certainty, Compliance, and Effectiveness, Objective 3.3:

Prioritize Robust Science, of EPA’s FY 2018-22 Strategic Plan. Awards made under this announcement will further EPA’s priorities supporting robust science for chemical safety.

All applications must be for projects that support the goal and objective identified above.

EPA also requires that grant applicants adequately describe environmental outputs and outcomes to be achieved under assistance agreements (see EPA Order 5700.7A1, Environmental Results https://www.epa.gov/planandbudget/strategicplan.html under Assistance Agreements, https://www.epa.gov/grants/epa-order-57007a1-epas-policy-environmental-results-under-epa-assistance-agreements). Applicants must include specific statements describing the environmental results of the proposed project in terms of well-defined outputs and, to the maximum extent practicable, well-defined outcomes that will demonstrate how the project will contribute to the priorities described above.

The Agency is soliciting research that proposes the development of tools to evaluate, monitor and assess risk, as well as potential outcomes from the use of synthetic biology products.

Examples of tools include models, bioinformatic systems, field-based and in vitro methods supporting risk assessments of synthetic biology products.

Applicants should address at least one of the three research areas, including at least one subtopic, described below. Applications may respond to one research area or integrate across two or three research areas. Applications should clearly indicate which research area(s) the application is addressing. Applications that address more than one research area will not necessarily be rated more highly than those that address just one of the areas. This RFA does not support any research which could also be used to facilitate intentional harm to public health and safety, agricultural crops and other plants, animals, the environment, material (including food, water, supplies, or material of any kind), or national security. For the purposes of this RFA, biotechnology products of interest include: industrial or consumer chemicals; pesticides (including pesticide intermediates); and new microbes used in biomass conversion for chemical production, microbial fuel cells, mining and resource extraction, building materials, waste remediation and pollution control, and non-pesticidal agriculture applications (e.g., biofertilizers, weather and climate modification).

1. Long-term stability, persistence, efficacy, and reliability of microbial biocontainment strategies, microbial synthetic genetic constructs, or microbial genetic restriction technologies:

a. Long-term stability, persistence, and reliability of synbio microbial biocontainment strategies (e.g., xenonucleic acids, noncanonical amino acids, recoded microorganisms) for synbio microorganisms. For the purposes of this RFA, biocontainment methodologies are those that prevent unintended proliferation of genetically modified organisms in the environment.

b. Stability and persistence of synthetic genetic constructs in microbes (e.g., are synthetic transgenes eliminated from viral, bacterial, algal or fungal genomes over time?). For the purposes of this RFA, “synthetic genetic constructs” are defined as new biological entities, not directly derived from extant organisms, such as enzymes, genetic circuits, and cells or the redesign of existing biological systems for useful purposes.

c. Efficacy of genetic restriction technologies or orthogonal gene constructs in precluding horizontal gene transfer from synthetic microorganisms. Horizontal gene transfer is a process in which organisms exchange genetic material with other species. For the purposes of this RFA, “genetic restriction technologies” are defined as methods that impede transgene movement. Particularly with self-https://www.epa.gov/grants/epa-order-57007a1-epas-policy-environmental-results-under-epa-assistance-agreements https://www.epa.gov/grants/epa-order-57007a1-epas-policy-environmental-results-under-epa-assistance-agreements replicating microbial systems, re-engineered cells may produce undesired consequences if they escape or overwhelm their intended host environment.

2. Ecological effects/impacts of synbio organisms or by-products that are released into the environment:

a. Survival, persistence, and unintended ecological effects of synbio microorganisms, plants and animals.

b. Unintended environmental effects/potential impacts of synthetic microorganisms, plants and animals such as: bacteriophages, plant viruses, entomopathogens, bacterial or fungal colonizers, (e.g., rhizobia, other nitrogen-fixing bacteria, mycorrhizae), higher plants, mosquitoes, or rodents.

3. Risks to human health from novel biomolecules produced using metabolic or genetic pathways by organisms used as manufacturing bioreactors. Much work regarding toxicity and allergenicity of new protein domains relies on bioinformatics that use existing databases of known toxins and allergens. These databases, or the literature, do not apply to biomolecules made by synbio organisms. Methods and models are needed to determine potential physiological responses, such as:

a. Adverse responses, including protein toxicity/allergenicity, biosynthetically produced proteins, atypical nucleotides, or noncanonical amino acids (i.e., non-standard amino acids and possibly other ligands),

b. Predictive toxicity motif detection in instances where noncanonical amino acids are incorporated into peptides/proteins,

c. Synbio microorganism colonization of the human microbiome.

Potential outputs expected from the research funded under this RFA may include:

• Tools and methods able to assess and monitor the effects of synthetic biotechnology products.

• Methods and models able to identify and quantify probable outcomes, sources of uncertainty, and trace cause and effect pathways.

• New or redesigned systems able to generate information on synthetic biology products and components that help determine potential adverse human and ecological effects.

• Advanced, useful evaluation and monitoring methods to assess risk to human health and the environment of beneficial synthetic biology products.

Potential outcomes expected from the research funded under this RFA may include:

• Improved understanding of risks to human health and the environment from synthetic biotechnology production processes.

• Better identification of key connections in the continuum between the production of synthetic biotechnology products and intermediate substances with potential adverse outcomes in humans.

To the extent practicable, research applications 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 applications must include a discussion on how the proposed research is innovative (see Section IV.C.6.a). Reviewers will draw from the above-mentioned innovation definition in the review/evaluation process of research applications (see Section V.A).

E. References

Congressional Research Service, Advanced Gene Editing: CRISPR-Cas9, https://crsreports.congress.gov, December 7, 2018.

Congressional Research Service, Major Agricultural Trade Issues in the 116th Congress, https://crsreports.congress.gov, May 20, 2019.

Drinkwater et al, Synthetic Biology Project, Creating A Research Agenda for the Ecological Implications of Synthetic Biology, Joint Workshops by the MIT Program on Emerging Technologies and the Wilson Center’s Synthetic Biology Project, SYNBIO May 7, 2014.

Engineering Biology Research Consortium, Engineering Biology; A Research Roadmap for the Next‐Generation Bioeconomy, June 2019, https://roadmap.ebrc.org/.

European Commission’s Scientific Committee on Emerging and Newly Identified Health Risks, Scientific Committee on Health and Environmental Risks, Scientific Committee on Consumer Safety, Synthetic Biology III: Risks to the environment and biodiversity related to synthetic biology and research priorities in the field of synthetic biology, doi:10.2875/590512.

Evans, B. et al, Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population, Scientific Reports, volume 9, Article number: 13047, September 10, 2019.

Executive Order on Modernizing the Regulatory Framework for Agricultural Biotechnology Products. June 11, 2019 https://www.whitehouse.gov/presidential-actions/executive-order-modernizing-regulatory-framework-agricultural-biotechnology-products/

Gronvall, G. Maintaining US Leadership in Emerging Biotechnologies to Grow the Economy of the Future. Health Security. Volume: 15 Issue 1: February 1, 2017.

Jones, et al., Does the U.S. public support using gene drives in agriculture? And what do they want to know? Sci. Adv. 2019; 5: eaau8462, 11 September 2019.

Morton, O., et al, Redesigning life, The promise and perils of synthetic biology, The Economist, April 4, 2019.

National Academies of Sciences, Engineering and Medicine (2016). Making the Living World Engineerable: Science, Practice, and Policy: Proceedings of a Workshop in Brief.

Washington, DC: The National Academies Press. https://doi.org/10.17226/24656.

https://crsreports.congress.gov/ https://crsreports.congress.gov/ https://roadmap.ebrc.org/ https://www.whitehouse.gov/presidential-actions/executive-order-modernizing-regulatory-framework-agricultural-biotechnology-products/ https://www.whitehouse.gov/presidential-actions/executive-order-modernizing-regulatory-framework-agricultural-biotechnology-products/ https://doi.org/10.17226/24656

National Academies of Sciences, Engineering, and Medicine (2017). Preparing for Future Products of Biotechnology. The National Academies Press: Washington, DC. The National Academies Press. https://doi.org/10.17226/24605.

National Academies of Science, Engineering, and Medicine (2017). Preparing for Future Products of Biotechnology, The National Academies Press. https://doi.org/10.17226/24605.

National Research Council (2015). Industrialization of Biology: A Roadmap to Accelerate the Advanced Manufacturing of Chemicals. Washington, DC: The National Academies Press.

https://doi.org/10.17226/19001.

Schmidt, Markus (editor), Synthetic biology: industrial and environmental applications, Wiley-VCH, 2012.

Trump BD, Cegan J, Wells E, Poinsatte-Jones K, Rycroft T, Warner C, Martin D, Perkins E, Wood MD, Linkov I. Co-evolution of physical and social sciences in synthetic biology.

Critical reviews in biotechnology. 2019 Apr 3;39(3):351-65.

U.S. Accountability Office, Report to the Subcommittee on Research and Technology, Committee on Science, Space, and Technology, House of Representatives (2018). Science and Technology. Considerations for Maintaining U.S. Competitiveness in Quantum Computing, Synthetic Biology, and Other Potentially Transformational Research Areas.

GAO-18-656; https://www.gao.gov/assets/700/694962.pdf U.S. Army Corps of Engineers, Engineer Research and Development Center (2019).

Synthetic Biology: Research Needs for Assessing Environmental Impacts. ERDC/EL TR-19-

10. http://dx.doi.org/10.21079/11681/33681

USDA, FDA, EPA (2020) The Unified Website for Biotechnology Regulation;

https://www.usda.gov/media/press-releases/2020/01/09/usda-fda-epa-launch-website-biotechnology-regulationU.S. EPA, Environmental Protection Agency (2019). Regulation of Biotechnology under TSCA and FIFRA; available at https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra.

U.S. EPA, Environmental Protection Agency (2018). U.S. Environmental Protection Agency’s FY 2018 – FY 2022 Strategic Plan. EPA-190-R-18-003.

U.S. EPA, Environmental Protection Agency (2017). Modernizing the Regulatory System for Biotechnology Products: Final Version of the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology.

U.S. EPA, Environmental Protection Agency (2017). Update to the Coordinated Framework for the Regulation of Biotechnology. https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/update-coordinated-framework-regulation-biotechnology https://doi.org/10.17226/24605 https://doi.org/10.17226/24605 https://doi.org/10.17226/19001 https://www.gao.gov/assets/700/694962.pdf http://dx.doi.org/10.21079/11681/33681 https://gcc01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.usda.gov%2Fmedia%2Fpress-releases%2F2020%2F01%2F09%2Fusda-fda-epa-launch-website-biotechnology-regulation&data=02%7C01%7CKlieforth.Barbara%40epa.gov%7Cad52dbc3246e4e6427e908d7ebbdc5b4%7C88b378b367484867acf976aacbeca6a7%7C0%7C0%7C637237072600391144&sdata=UgxGoSxxLeFetNMlJm1UJtZo1JHr6Zzmo1%2F54SXJ7s8%3D&reserved=0 https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra https://www.epa.gov/sites/production/files/2018-08/documents/fy-2018-2022-epa-strategic-plan-print.pdf https://www.epa.gov/sites/production/files/2018-08/documents/fy-2018-2022-epa-strategic-plan-print.pdf https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/national-strategy-modernizing-regulatory-system https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/national-strategy-modernizing-regulatory-system https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/update-coordinated-framework-regulation-biotechnology https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/update-coordinated-framework-regulation-biotechnology

U.S. EPA, Environmental Protection Agency (2017). FIFRA Scientific Advisory Panel Meetings Related to Biopesticides; available at https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/fifra-scientific-advisory-panel-meetings-related.

U.S. EPA, Environmental Protection Agency (2005). Reiter, L W., J R. Fowle* III, M J.

Bagley, A Fairbrother, E Z. Francis, R J. Frederick, J A. Glaser, MJK Selgrade, S K. Sikdar*, L S. Watrud, AND J. L. Andersen. Biotechnology Research Program; available at https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NHEERL&dirEntryId=123522

Wozniak CA, McClung G, Gagliardi J, Segal M, Matthews K. Regulation of genetically engineered microorganisms under FIFRA, FFDCA and TSCA. In Regulation of agricultural biotechnology: the United States and Canada 2012 (pp. 57-94). Springer, Dordrecht.

Wright O, Stan GB, Ellis T. Building-in biosafety for synthetic biology. Microbiology.

1;159(7):1221-35. July 2013.

F. Special Requirements

It is EPA Policy to ensure that the results of EPA-funded extramural scientific research are accessible to the public to the greatest extent feasible consistent with applicable law; policies and Orders; the Agency’s mission; resource constraints; and U.S. national, homeland and economic security. This entails maximizing, at no charge, access by the public to peer-reviewed, scientific research journal publications or associated author manuscripts, and their underlying digital research data, created in whole or in part with EPA funds, while protecting personal privacy;

recognizing proprietary interests, confidential business information and intellectual property rights; and avoiding significant negative impact on intellectual property rights, innovation and U.S. competitiveness. EPA’s Policy for Increasing Access to Results of EPA-Funded Extramural Scientific Research may be accessed at: https://www.epa.gov/research/non-epa-researcher-requirements. Terms and conditions implementing this policy may be accessed at:

https://www.epa.gov/research/non-epa-researcher-requirements.

Applications submitted under this announcement shall include a Scientific Data Management Plan (SDMP) that addresses public access to EPA-funded scientific research data. See the SDMP clause in Section IV for details on the content of an SDMP. Applicants will also be asked to provide past performance information on whether journal publications or associated author manuscripts, and the associated underlying scientific research data and metadata, under prior assistance agreements were made publicly accessible. These items will be evaluated prior to award.

Reasonable, necessary and allocable costs for data management and public access as discussed in EPA’s Policy for Increasing Access to Results of EPA-Funded Extramural Scientific Research, may be included in extramural research applications and detailed in the budget justification described in Section IV.

Agency policy and ethical considerations prevent EPA technical staff and managers from providing applicants with information that may create an unfair competitive advantage.

https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/fifra-scientific-advisory-panel-meetings-related https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/fifra-scientific-advisory-panel-meetings-related https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/fifra-scientific-advisory-panel-meetings-related https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/fifra-scientific-advisory-panel-meetings-related https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/regulation-genetically-engineered-microorganisms-under https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/regulation-genetically-engineered-microorganisms-under https://www.epa.gov/research/non-epa-researcher-requirements https://www.epa.gov/research/non-epa-researcher-requirements https://www.epa.gov/research/non-epa-researcher-requirements

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). If you choose to submit a Multiple PI application, you 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 (https://www.epa.gov/research-grants/research-grants-guidance-and-policies).

Please note: Early career awards will not accommodate a Multiple PI application. Early career awards shall be submitted as a single Lead PI application. Special eligibility criteria apply to the early career portion of this RFA. Please see Section III of this RFA for details on the early career eligibility criteria. The application must include an early career verification (see “Early Career Verification” in Section IV.C.6.e).

This solicitation provides the opportunity for the submission of applications for projects that may involve human subjects research. All applications must include a Human Subjects Research Statement (HSRS; described in Section IV.C.6.c of this solicitation). 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.D and V.F of this solicitation.

II. AWARD INFORMATION

It is anticipated that a total of approximately $4.4 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 7 awards (4 regular and 3 early career) under this RFA. Requests for amounts in excess of a total of $760,000 for regular awards and a total of $453,333 for early career awards, including direct and indirect costs, will not be considered. The total project period requested in an application submitted for this RFA may not exceed 3 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 applications by funding discrete portions or phases of proposed projects. If EPA decides to partially fund an application, it will do so in a manner that does not prejudice any applicants or affect the basis upon which the application, or portion thereof, was evaluated and selected for award, and therefore maintains the integrity of the competition and selection process.

EPA intends to award only grants 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 rather than substantial to achieving the goals of the research under a grant. Interaction that is “incidental” does not involve resource commitments by EPA.

III. ELIGIBILITY INFORMATION

A. Eligible Applicants

Public and private nonprofit institutions/organizations, public and 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 and individuals are not eligible to apply.

Non-profit organization, as defined by 2 CFR 200.70, means any corporation, trust, association, cooperative or other organization that: (1) is operated primarily for scientific, educational, service, charitable or similar purposes in the public interest; (2) is not organized primarily for profit; and (3) uses its net proceeds to maintain, improve and/or expand its operations. Note that 2 CFR 200.70 specifically excludes Institutions of Higher Education from the definition of non-profit organization because they are separately defined in the regulation. While not considered to be a non-profit organization(s) as defined by 2 CFR 200.70, public or nonprofit Institutions of Higher Education are, nevertheless, eligible to submit applications under this RFA. Hospitals operated by state, tribal, or local governments or that meet the definition of nonprofit at 2 CFR

200.70 are also eligible to apply as nonprofits or as instrumentalities of the unit of government depending on the applicable law. For-profit colleges, universities, trade schools, and hospitals are ineligible. 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. Federal employees may not receive salaries or augment their Agency’s appropriations through awards made under this program unless authorized by law to receive such funding.

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.

The early career awards will support research performed by PIs with outstanding promise at the Assistant Professor or equivalent level. Principal investigators from applicant institutions applying for the early career portion of the RFA must meet the following additional eligibility requirements:

1. Hold a doctoral degree in a field related to the research being solicited by the closing date of the RFA;

2. Be untenured at the closing date of the RFA; and

3. By the award date, be employed in a tenure-track position (or tenure-track-equivalent position) as an assistant professor (or equivalent title) at an institution in the U.S., its territories, or possessions. Note: For a position to be considered a tenure-track-equivalent position, it must meet all of the following requirements: (1) the employing department or organization does not offer tenure; (2) the appointment is a continuing appointment; (3) the appointment has substantial educational responsibilities; and (4) the proposed project relates to the employee's career goals and job responsibilities as well as to the goals of the department/organization.

The application must include an early career verification (see “Early Career Verification” in Section IV.C.6.e).

Potential applicants who are uncertain of their eligibility should contact Ron Josephson in ORD, phone: 202-564-7823, email: josephson.ron@epa.gov.

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. In addition, applications must be submitted mailto:josephson.ron@epa.gov through Grants.gov as stated in Section IV of this announcement (except in the limited circumstances where another mode of submission is specifically allowed for as explained in Section IV) on or before the application submission deadline published in Section IV of this announcement. Applicants are responsible for following the submission instructions in Section IV of this announcement (see Section IV.F. “Submission Instructions and Other Submission Requirements” for further information) to ensure that their application is submitted timely.

Applications submitted after the submission deadline will be considered late and deemed ineligible without further consideration unless the applicant can clearly demonstrate that it was late due to EPA mishandling or because of technical problems associated with Grants.gov or relevant SAM.gov system issues. An applicant’s failure to timely submit their application through Grants.gov because they did not timely or properly register in SAM.gov or Grants.gov will not be considered an acceptable reason to consider a late submission.

Also, applications exceeding the funding limits or project period term described herein will be rejected 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 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 https://www2.epa.gov/grants/epa-solicitation-clauses.

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 are in Section F.

A. Grants.gov Submittal Requirements and Limited Exception Procedures Applicants, except as noted below, must apply electronically through Grants.gov under this funding opportunity based on the grants.gov instructions in this announcement. If an applicant does not have the technical capability to apply electronically through grants.gov because of limited or no internet access which prevents them from being able to upload the required application materials to Grants.