Frequently Asked Questions

1.  What is the NIH Common Fund?

The NIH Common Fund is a funding entity within NIH that supports bold scientific programs that catalyze discovery across all biomedical and behavioral research. These programs create a space where investigators and multiple NIH Institutes, Centers, and Offices collaborate on innovative research expected to address high priority challenges for NIH as a whole and make a broader impact in the scientific community.

2. What does the NIH Common Fund do?

• We make substantial investments in time-limited, goal-driven programs in order to change significantly the trajectory of biomedical research.
• Our programs accelerate emerging science, enhance the biomedical research workforce, remove research roadblocks, and support high-risk high-reward science in ways that no other entity is likely or able to do.
• We gather diverse input from NIH leadership, staff, and the broad biomedical research community to plan our programs.
• We assemble consortia of multidisciplinary, innovative researchers who collaborate to tackle a shared, ambitious goal.
• We manage our programs in partnership with nominated experts from the NIH Institutes and Centers
• We design our programs so that each deliverable will spur subsequent biomedical advances that otherwise would not be possible without our strategic investment.
• For more information on the Common Fund, visit: https://commonfund.nih.gov/about 

3. What are New Approach Methodologies (NAMs)?

NAMs are laboratory (in vitro and in chemico) or computer-based (in silico) research approaches intended to more accurately model human biology, and complement, or in some cases, replace traditional research models. NAMs provide alternative, and in some cases, more advanced methods of modeling human health and disease. NAMs, which broadly span in chemico, in vitro, and in silico approaches, have proven to be valuable tools in fundamental, translational, clinical, and toxicological research, and are being used to study human biology and in risk assessments for efficacy and toxicity of novel therapeutics. NAMs are sometimes referred to as Novel Alternative Methods or Non-Animal Methods.

4. What is the NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) Program?

The NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) program will accelerate the development, standardization, validation, and use of human-based New Approach Methodologies (NAMs).

NAMs are laboratory (in vitro and in chemico) or computer-based (in silico) research approaches intended to more accurately model human biology, and complement, or in some cases, replace traditional research models. The Complement-ARIE program will build upon ongoing efforts in the field related to NAMs, while identifying opportunities for innovation and coordination amongst the various collaborators.

Complement-ARIE will significantly advance understanding of human health and disease by providing a range of mature and/or validated and standardized biomedical research models. Developing these models will require multi-disciplinary expertise in disease research, personalized medicine, and in screening therapeutics for safety and effectiveness.

5. What is the goal of the Complement-ARIE Program?

The overall Complement-ARIE program goal is to catalyze the development, standardization, validation, and use of human-based NAMs that will transform fundamental, translational, and clinical sciences. The program goals include: 

• Better model and understand human health and disease outcomes across diverse populations.
• Develop NAMs that provide insight into specific biological processes or disease states.
• Validate mature NAMs to support regulatory use and standardization.
• Complement traditional models and make biomedical research more efficient and effective. 

6. How did the NIH arrive at these scientific and operational needs to advance NAMs?

Common Fund strategic planning is undertaken regularly to identify research areas that address key roadblocks in biomedical research or that represent emerging scientific opportunities ripe for Common Fund investments. NAMs were identified as an area of research that would benefit from Common Fund investment for a variety of reasons:

• The past decade has seen dramatic advances in areas such as complex in vitro systems, bioengineering technologies, human data, and computational methods.
• Existing programs in the Common Fund Data Ecosystem and others represent a wealth of data to support and enable complementary NAMs.
• We are at a watershed moment in the history of drug discovery and development where the FDA Modernization Act 2.0 is a gamechanger in legislating that drugs may be registered without animal studies.

Simultaneous to early planning stages of the Complement-ARIE program, the NIH sought the assistance of the Advisory Committee to the Director (ACD) on catalyzing the development and use of Novel Alternative Methods to Advance Biomedical Research to identify areas in which the development and use of novel alternative methods will provide the most value to biomedical research. 

• The ACD working group recommendations are aligned with Complement-ARIE program goals and have been incorporated into the program planning structure.

7. What are major components for the Complement-ARIE Program and what are the goals of these components?

The Complement-ARIE Program consists of three major initiatives: 

• NAMs Comprehensive Technology Development Centers
• NAMs Data Hub and Coordinating Center (NDHCC)
• Validation and Qualification Network (VQN)

Complement-ARIE will also have a component on strategic engagement with key partners from other federal agencies including regulatory bodies, industry, non-profits, and other non-governmental organizations (NGOs) to advance emerging opportunities in development and use of NAMs in basic, translational, and clinical research.

The goal of the NAMs Comprehensive Technology Development Centers is:

• To stimulate the development of combinatorial NAMs to support the areas of greatest need, with emphasis on increased biological complexity and throughput, innovative combinatorial approaches, and data sharing according to FAIR principles. Training and outreach components will be required to facilitate dissemination, capacity building, and adoption.
• Components of Technology Development Centers
  • Integrated NAMs Technology Development
    • NAMs technology development
    • Technology pilot projects
  • Center Core Facilities
    • Administration
    • Data collection and bioinformatics
    • Resources
  • Technical Characterization
  • Training and Outreach
    • Workforce development and training
    • Community and collaborator engagement research
    • Ethical, Legal, and Social Implications (ELSI)

The goal of the NAMs Data Hub and Coordinating Center (NDHCC) is: 

• To create integrated data structures and a central data hub, establish standards for data reporting and model credibility, enhance the FAIRness (Findability, Accessibility, Interoperability, and Reusability) of NAMs-relevant data, develop strategies for interoperability and data reuse, build a searchable repository for New Approach Methodologies (NAMs), develop tools for data analytics, dissemination, and sharing, and foster community collaborations.
• Facilitate NAMs data submissions from tech dev centers and other sources, including those coming from the VQN and partner organizations
• Establish common data elements:
  • Data standards and annotations
  • Data analyses and visualization tools
• Identification and integration of relevant preclinical and clinical datasets
• Reference, training, and validation datasets

The goal of the Validation and Qualification Network (VQN) is: 

• To work with regulatory authorities, industry partners, and other collaborators to establish and apply validation/qualification frameworks and develop a framework to evaluate use cases from the technology development centers and the collaborator community that encourages adoption of NAMs for regulatory, industrial, and biomedical research use.
• Accelerate deployment and implementation of NAMs in both research and regulatory contexts.
• Develop standardized reporting and common data elements for preclinical, clinical, and safety performance.
• Perform conformity assessments and develop quality management systems.
• Work with collaborators for commercial market entrance and surveillance.

The goal of strategic engagement is: 

• To identify emerging gaps and opportunities, workforce development needs, (including training and community engagement) in the development of novel and/or combinatorial NAMs to catalyze the development, standardization, validation, and use of human-based NAMs through innovative technologies and partnerships. Strategic engagement activities will support programmatic gap areas and allow Complement-ARIE to dynamically respond to any emerging opportunities that surface throughout the duration of the program.    

8. How will the Complement-ARIE components interact with each other?

Program Flow Diagram: The diagram illustrates the key components of the Complement-ARIE program including technology development, centralized data resources, validation and qualification along with key training and dissemination activities to provide a fluid conduit from collaborator engagement to implementation.

9. How long will the program last?

The first phase of the Program was cleared at the January 2024 Council of Councils  for five years. If the first phase is successful, there will be a proposal for a second phase to be considered by the Council of Councils.

10. Where can I find more information?

Announcements and regular updates will be posted on the program website:  https://commonfund.nih.gov/complementarie

11. Who should I contact with questions?

• General inquiries can be sent to [email protected]. Scientific and Research contacts for individual Notice of Funding Opportunity (NOFO) are indicated in each announcement. These individuals should be your first contact for questions related to the NOFO.
• In addition, the Common Fund Complement-ARIE Program is administered via a team of NIH program experts. The NIH Complement-ARIE Program Working Group members and their affiliations are listed at: https://commonfund.nih.gov/complementarie/members
• You can also sign up for the Complement-ARIE listserv to stay up to date on future announcements.

12. What type of NAMs will Complement-ARIE support?

Complement-ARIE will support the development, standardization, and validation of NAMs in the following categories:

• Complex in vitro models, such as microphysiological systems (MPS), organoids and other advanced 3-D models using human-derived cells and tissues that emulate human organ structure, function and response to study both normal physiology and disease pathology.  
• In silico multi-scale systems simulating and modeling healthy/diseased individuals through approaches such as physiological-based pharmacokinetic (PBPK) modeling and digital twin approaches.
• In chemico cell-free systems capturing dynamic changes to assess chemical toxicity, chemical hazard and risk assessment, and inform adverse outcome pathways (AOP).
• Integrated findable, accessible, interoperable, and reusable (FAIR) datasets and artificial intelligence (AI)-engines to generate testable predictions (i.e., patient digital twin with tissue chips (MPS) and avatar approaches).
• Combinatorial approaches that combine two or more of the above approaches. 
   

 

What is the Complement-ARIE Validation and Qualification Network (VQN)?

The VQN is a component of the Complement-ARIE program that will accelerate deployment and regulatory approval of NAMs for biomedical research. The goal of the VQN is to work with regulatory authorities, industry partners, and other collaborators to establish and apply validation/qualification frameworks to NAMs and to develop a framework to evaluate use cases from the technology development centers and the collaborator community that encourages adoption of NAMs for regulatory, industrial, and biomedical research use.

What will the VQN do?

Goals of the VQN include:

• Accelerate deployment and implementation of NAMs in both research and regulatory contexts.
• Develop standardized reporting and common data elements for preclinical, clinical, and safety performance.
• Perform conformity assessments and develop quality management systems.

Will the VQN validate or qualify specific NAMs?

No. It is important to note, the VQN will NOT serve as the body that will validate and/or qualify any specific NAMs within regulatory contexts. U.S. federal agencies operate under statutes and regulations particular to each agency, and therefore have different criteria for a NAM to be acceptable and applicable toward each agency's individual regulatory requirements.  In some cases, even within an agency (e.g. different centers of FDA) there may be different needs depending on the area of regulation.  Even though a NAM may be validated to address a specific endpoint for one (or multiple) context(s) of use under a particular guidance/regulation, it may not be considered acceptable under a different guidance/regulation among various agencies, regulatory jurisdictions, and countries.

What is the title of this Notice of Funding Opportunity (NOFO)?

Complement-ARIE New Approach Methodologies (NAMs) Technology Development Centers (UM1 Clinical Trial Optional).

What is the announcement number of this NOFO?

RFA-RM-24-010

What is the purpose of this announcement?

The purpose of this NOFO is to establish Comprehensive NAMs Technology Development Centers to support NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) program. The Complement-ARIE program will accelerate the development, standardization, validation, and use of human-based New Approach Methodologies (NAMs). Complement-ARIE will significantly advance understanding of human health and disease by providing a range of mature and/or validated and standardized biomedical research models. 

The Comprehensive NAMs Technology Development Centers will stimulate the development of combinatorial NAMs to support scientific areas of need, with emphasis on increased biological complexity and throughput, innovative combinatorial approaches, and data sharing according to FAIR principles. Developing these NAMs will require multi-disciplinary expertise in disease research, personalized medicine, screening therapeutics for safety and efficacy, and regulatory science. 

Whom can I reach out to with questions about this announcement?

All questions are welcome. For scientific/research questions, please reach out to Danilo A. Tagle, [email protected] and Christine Happel, [email protected]. For general questions, please reach out to [email protected].

When are applications due?

NIH has published a Notice of Change to Receipt Date and Expiration Date for RFA-RM-24-010. The new receipt date is March 18, 2025. All applications are due by 5:00 PM local time of applicant organization. 

What are the key dates in the timeline for planning our application?

NOFO Announcement Released			December 10, 2024
Open Date (Earliest Submission Date):			January 28, 2025
Letters of Intent (LOI) Due - not required			January 24, 2025
Application Due Dates:			Review and Award Cycles:
New	Renewal / Resubmission / Revision  (as allowed)	AIDS-New / Renewal / Resubmission / Revision (as allowed)	Scientific Merit Review	Advisory Council Review	Earliest Start Date
March 18, 2025	Not Applicable	Not Applicable	July, 2025	October, 2025	December 2025
All applications are due by 5:00 PM local time of applicant organization.  Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.  No late applications will be accepted for this NOFO.
Expiration Date:			March 19, 2025
Due Dates for E.O. 12372			Not Applicable

What organizations are eligible for this funding opportunity?

• Higher Education Institutions
  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education
• The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
• Nonprofits Other Than Institutions of Higher Education
  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• For-Profit Organizations
  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)
• Local Governments
  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
• Federal Government
  • Eligible Agencies of the Federal Government, including the NIH, FDA, and EPA intramural programs
  • U.S. Territory or Possession
• Other
  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations

Are foreign organizations eligible?

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

What registrations are required for this funding opportunity?

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information. 

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Who is eligible to be a Program Director/Principal Investigator?

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including individuals from underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

The PD/PI (the contact PI if a multi-PI application) must devote at least 2.4 person months (20%) of full-time calendar month effort to the program.

Does this funding opportunity have cost sharing requirements?

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

Are there restrictions of the number of applications submitted to this funding opportunity?

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).
   

How do I request an application package?

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. 

What should the content and form of application submission be?

It is critical that applicants follow the Research (R) Instructions in the How to Apply - Application Guide except where instructed in the notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Are Letters of Intent (LOI) required?

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

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

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

The letter of intent should be sent to:
Danilo A. Tagle, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Email: [email protected]

What are the page limitations for my specific aims and research strategy of my application?

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

Specific Aims. Briefly summarize the aims for the entire application, including all Elements and Modules. 1 page

Research Strategy. The Research Strategy must consist of the following sections with the indicated page limits:

• Element A. Overview; one required, 5 pages
• Element B. Strategic Management; one required, 3 pages
• Element C. Integrated NAM Technology Development; one required, 10 pages
• Element D. Center Core Facilities; one required, 10 pages
• Element E. Technical Characterization; one required, 6 pages
• Element F. Training & Outreach; one required, 5 pages

Please refer to the notice of funding opportunity for additional information on page limits for other sections.

What is a Milestone Plan?

The applicant is required to provide detailed information and timelines for completing all proposed activities according to the specific aims. Applicants must include specific yearly milestones that will need to be met in order to accomplish the work set out in a five-year period. Milestones that reflect progress in each specific aim should be easily measurable and realistic. Project milestones that quantitatively measures progress towards each of the proposed specific aims are required. A timeline to achieve the proposed milestones, in the form of a Gantt chart, is also required.

Is a Plan for Enhancing Diverse Perspectives (PEDP) required?

This Notice of Funding Opportunity (NOFO) does not require a PEDP.

Is Cost Share required in the R&R Budget?

Applicants are reminded that although Cost Share is not required; if these types of costs are included in the research application and peer reviewed, it is expected that these costs will not be covered by NIH. Please refer to the notice of funding opportunity for guidance on individual budget elements.

Is a Resource Sharing Plan required?

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

What if a submission date falls on a weekend or Federal holiday?

When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

How do I submit my application?

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Are there specific considerations for applications involving the NIH Intramural Research Program?

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this NOFO. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above and, in the NIH, Intramural Source Book.

Are mandatory disclosures required?

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].
 

For the External Advisory Committee (EAC), what is the definition of a “non-scientist”? Would faculty outside of the collaboration group but at the same institution be considered “external”?

The EAC should be a panel of subject matter experts with expertise specific to the project who can provide scientific evaluation, feedback on necessary changes, and advice to keep the project competitive with other technologies. Scientific experts on the EAC must come from outside of the primary collaboration group but can be at the same institution as one or more of the principal investigators (PIs). Non-scientists should provide expertise on non-scientific aspects of the project, such as the commercialization, social and ethical implications, and utilization of technology. Examples of non-scientist EAC members could include potential investors, non-profit or advocacy organizations, bioethicists, or paid consultants. Applicants are not required to name specific EAC members, but letters of support from potential EAC members can be included for evaluation and review.

Are there a recommended number of resource cores? Is the 10-page limit on the application for each individual core or for all cores combined? 

The number of proposed cores will differ based on the project and area of need. The 10-page limit should include information on all necessary cores.

Does the Notice of Funding Opportunity (NOFO) anticipate multiple-PI projects? If so, what would be an expected number of PIs on a given application? 

The Complement-ARIE NOFO anticipates a significant number of multiple-PI applications in order to meet program needs. The ideal application will include a multidisciplinary team that has the expertise to form a Technology Development Center (TDC) that encompasses the six required elements and their associated modules. This expertise should include developing the new approach methodology (NAM) technology, as well as its validation, qualification, utility, and dissemination.  

Are small businesses eligible to apply if they are incorporated in the United States and have additional lab space in Europe? Is this covered by the definition of a “foreign component”?

The main application for the Complement-ARIE program must be from a U.S.-based institution or business; however, the main applicant can have collaborations with academic or commercial entities outside the United States. However, these foreign components must provide a unique resource or expertise that cannot be found elsewhere in the United States.

Can researchers from the U.S. Food and Drug Administration (FDA) apply for this NOFO? 

Yes. This program is open to scientists from federal agencies with intramural research programs, including NIH, FDA, and the Environmental Protection Agency (EPA).

If a project focuses on a disease such as cancer, is lifespan a required variable? 

The lifespan is a scientific priority area for the Complement-ARIE program, which includes the chronicity or long-term effects of a disease or condition. Including lifespan or any of the other scientific priority areas in a project is not a requirement.

Are TDCs required to deposit their data in the NAMs Data Hub and Coordinating Center or can the data be deposited elsewhere?

TDCs are strongly encouraged to utilize the NAMs Data Hub, which will serve as a centralized federated database for NAM-related data and products. In addition to serving as a data repository, the NAMs Data Hub will include analytical tools, dashboards, and other tools for analyzing and disseminating data. Applications should indicate how the TDC will interface with the NAMs Data Hub and Coordinating Center, such as the planned frequency of data submission.

What is a succession plan? 

A succession plan is part of TDC management and is a defined plan for replacing trainees or PIs who might step down from their current position or move elsewhere during the 5-year project period. 

Is it considered a strength to develop NAMs that could be commercialized? Is it considered a weakness if commercialization is not a long-term goal?

The Compliment-ARIE program is intended to catalyze both the development and dissemination of NAMs for translational and clinical research. Funded NAMs must be fairly and widely disseminated and applications should include how the project team plans to make the NAM technology easily accessible and useful, such as through commercialization.

What criteria will be used to select reviewers? Will government employees be eligible to serve as reviewers?

Reviewers are recruited based on (a) their scientific and technical qualifications and (b) their expertise related to the submitted applications. Federal scientists can be recruited for review of extramural NIH grant applications.

To what extent should applications detail the interaction between the TDC and the planned Validation Qualification Network (VQN)?

TDCs will interact with the VQN when the NAM technology is eligible for the validation and quantification processes. Existing validation and qualification guidelines from FDA and the EPA may be used to determine eligibility while the VQN is being stood up.

Does the proposal need to include two NAMs using separate approaches (e.g., one in vitro and one in silico NAM) or can a proposal have two different NAMs from the same approach (e.g., two in chemico NAMs)?

The Complement-ARIE program is intended to fund projects leveraging a combination of various approaches. Project teams should focus on the added value of integrating a NAM approach into their existing driving technology. The application should include well-defined pilot projects that integrate additional NAM approaches into the driving technology.

What will be the process of sharing best practices between TDCs?

TDCs will function within a consortium along with the data hub and VQN. The consortium will establish pre-competitive environments where members are expected to share resources, expertise, and data to ensure that all consortium members are benefiting from their interactions.

Are applications from multiple institutions recommended, or is an application from a single institution acceptable?

In most cases, a project’s necessary expertise will require team members from multiple institutions, including small businesses. However, applications from a single institution are acceptable if the required expertise can be found entirely at that institution.

Would validation of a methodology flagged as a key element in an integrative complex data assessment scheme (e.g., the Organization for Economic Co-Operation and Development [OECD]) be within the scope of this funding opportunity?

Yes. The Compliment-ARIE program will be working with agencies that have existing validation guidelines (such as OECD) to incorporate those guidelines into the VQN.

Are the cores expected to provide services for external researchers, or will they only serve the Complement-ARIE projects?

The cores are intended to support the activities of the NAMs TDCs; they may choose to provide outside services, but those activities would be separate from their support of the TDCs.

How many awards will be funded?

The program anticipates funding five or six awards.

With the focus on broad use and transfer of technology between centers, will automated manufacturing be preferred or are microphysiological systems that are fabricated manually or in small batches (e.g., by 3D printing) considered acceptable?

Customized microphysiological systems or printed constructs would be appropriate for the initial data gathering and pilot project portions of the program. However, once the NAMs technology is ready for dissemination, having a scalable, automated manufacturing platform plan would be beneficial.

Does the NAM need to address multiple diseases or tissue areas, or can a NAM for one tissue area be proposed with future directions to expand or generalize to other tissue types?

Although the TDCs should be focused on a broad scientific area of need, the NAMs will need to be narrowed down to specific contexts of use for validation and clinical utility.

Are applicants eligible to collaborate with external small businesses to support the development of the data hub?

The Complement-ARIE Data Hub and Coordinating Center is being independently funded through a separate RFA.

If software is developed as part of the awarded work, will NIH assume responsibility for hosting the software following completion of the 5-year funding term?

The data and algorithms developed for NAM computational models will be submitted to the Complement-ARIE Data Hub. The Data Hub and database will be supported beyond the 5-year term of the program.

Are any areas of a NAM or combinatorial NAMs considered not favorable for inclusion in an application, or non-responsive to this NOFO?

To be responsive to this NOFO, applications must include the development of combinatorial NAMs that use two or more different NAMs, such as in vitro, in silico or in chemico approaches. Applications will be considered non-responsive and will not be reviewed if they include any animal-based NAMs, NAMs developed with animal cells, animal-based research, or in vivo animal studies.

Can a VQN member apply for this funding opportunity?

Yes. Applying for this program should not preclude future participation in the VQN.

Is Element C-1 asking for the development of a single combinatorial NAM, such as an in vitro and in silico model of a single organ or organ system? 

Element C-1 outlines the major NAM technology development, including the driving NAM technology. The combinatorial NAM will include the driving NAM integrated with a second, different NAM approach.

Does the combinatorial NAM technology need to be validated in vivo to demonstrate physiological relevance?

The NAM technology must be shown to have clinical utility and relevance for specific human diseases or conditions; consequently, the funding opportunity has been designated as clinical trial optional.

For the in silico component, are predictive mechanistic modeling approaches preferred, as opposed to data-driven and exploratory statistical learning approaches?

For this program, the preference is for mechanistic understanding. The in silico and computational elements should be used as predictive tools for the relevant human condition or disease state.

What is the major difference between in silico components for Element C-2 and the data collection and bioinformatics for Element D-2?

Element C-1 would include in silico approaches that are driving the combinatorial NAM technology. Element D-2 is more general and may include components such as early stage computational work or incorporation of multiple datasets. 

Do you expect pilot projects to be described in the application itself, or during the process through which they will be solicited, reviewed, and selected?

The pilot projects, particularly how they add value to the driving NAM technology, must be well-defined in the application so that they can be subject to peer review. These pilot projects are intended to be short (e.g., 1 to 2 years duration) and must demonstrate readiness for development and integration into the driving NAM. An application should include three to five pilot projects that are described in sufficient detail to be evaluated by peer review. In addition, Complement-ARIE anticipates providing administrative supplements in the future to facilitate incorporation of emerging technologies or opportunities. 

For Element C, is 10 pages the total page limit, or can each system have ten pages to cover multiple experimental systems?

Element C has a total page limit of 10 pages. This should include all organ systems and modules C1 and C2.

For the C2 module should I identify all three pilot project for the 5-year period, or should I describe one with an identified PI in detail, while providing brief conceptual abstracts for the other two without identifying PIs for these projects?

Pilot projects should be described for all 3 pilots. Each pilot is expected to have their own milestones and timeline. Additionally, there are NOFO-specific review criteria related to the pilot projects.

Because this funding opportunity has many defined elements, should the Specific Aims page refer to Element C and the pilots only?

The Specific Aims should include the entire project, including all elements. Each element should have specific milestones associated with it, including sub-aims, if appropriate.

Are equipment costs justifiable to include in this funding mechanism?

All purchase costs will need to be clearly justified. The ultimate goal of the program is to democratize the use of NAMs and, as much as possible, specialized tools and equipment need to address how they will equitably be made accessible to the general biomedical research community. The following rules of allowability must apply to equipment and other capital expenditures:

• Capital expenditures for general purpose equipment, buildings, and land are unallowable as direct charges, except with the prior written approval of the NIH awarding IC or pass-through entity.
• Capital expenditures for special purpose equipment are allowable as direct costs, provided that items that relate to a change in scope (which may be indicated by a unit cost of $25,000 or more) have the prior written approval of the NIH awarding IC or pass-through entity.
• Capital expenditures for improvements to land, buildings, or equipment which materially increase their value or useful life are unallowable as a direct cost except with the prior written approval of the NIH awarding IC, or pass-through entity. See Depreciation for rules on the allowability of depreciation on buildings, capital improvements, and equipment. See also Rental Costs of Real Property and Equipment.
• When approved as a direct charge pursuant to items (i) through (iii) above, capital expenditures will be charged in the period in which the expenditure is incurred, or as otherwise determined appropriate and negotiated with the NIH awarding IC.
• The unamortized portion of any equipment written off as a result of a change in capitalization levels may be recovered by continuing to claim the otherwise allowable depreciation on the equipment, or by amortizing the amount to be written off over a period of years negotiated with the Federal cognizant agency for indirect cost.
• Cost of equipment disposal. If the non-Federal entity is instructed by the NIH awarding IC to otherwise dispose of or transfer the equipment the costs of such disposal or transfer are allowable.

See also Capital Expenditures, Equipment, Special Purpose Equipment, General Purpose Equipment, Acquisition Cost, and Capital Assets.

Are there are restrictions on foreign collaborators for this funding announcement?

Foreign components/collaborations are allowed so long as they satisfy the requirements of unique expertise and/or resources that are not available in the US.

Do you have any suggestions for finding partners to team with?

The Complement-ARIE program does not have a partnering site. Find partners that have the right expertise and resources through social media, conferences, and networking events.

Given the high-priority scientific areas outlined in this initiative—such as chronicity, neuroscience, personalized health, and cross-disease pathogenesis—does this grant opportunity support research on diseases of prematurity, particularly those that involve long-term systemic effects, neurodevelopmental outcomes, and the integration of personalized health approaches?

These high-priority scientific areas were identified through the Complement-ARIE strategic planning process. However other areas of scientific interests where no animal models exists or perform poorly in predict human response will be of interest. The proposed NAMs should reliably and efficiently produce information that is fit for purpose while reducing animal use.

Will the milestone plan be used as go/no-go decision points in terms of continued funding during the initial 5-year program?

Within the NOFO Terms and Conditions are performance requirements that include the expectation that recipients meet yearly milestones as defined by investigators and NIH program officials and referenced in the Notice of Award. NIH program staff will monitor progress on the agreed upon milestones and help identify recourse, if needed. NIH Program staff retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award.

Can you please provide some information on the budget and what is allowed under the budget? Specifically, what is the total budget allowed? 

As per the RFA, application budgets are limited to $2M per year in direct costs but should reflect the actual needs of the proposed project.

There are 3 minimum pilot projects. Do they all need to be active in the same time period, or can they be staggered within the 5-year award period?

Pilot projects can be staggered within the 5-year award period and should be short-term activities of 1-2 years that can be integrated into the major driving NAMs technology.

If we are NAMs developers and do not have experience in Validating a NAM to a regulatory standard, what type of person or expertise would you recommend that we seek out, to achieve the right level of validation for the proposed system?

Regulatory expertise can be sought either as subject-matter experts (SMEs) on the project or through institutional regulatory cores.

Are experiments proposed with animal model use in NAM validation acceptable to propose if the animal model as the current standard?

As per the RFA, new animal-based NAMs, NAMs developed with animal cells, animal-based research, or in vivo animal studies proposed within the application will be considered non-responsive. Validation studies that include animal studies for diseases/conditions where an animal model is the gold standard may be considered at a later date as part of the validation studies performed in conjunction with the VQN for mature combinatorial NAMs with a specific context of use. However, validation studies that include animal comparators are outside the scope of RFA-RM-24-010. 

What is the title of this Notice of Funding Opportunity (NOFO)?

Complement-ARIE New Approach Methodologies (NAMs) Data Hub and Coordinating Center (U24 Clinical Trial Optional).

What is the announcement number of this NOFO?

RFA-RM-24-013

What is the purpose of this announcement?

The purpose of this NOFO is to establish the NAMs Data Hub and Coordinating Center (NDHCC) to support the NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) program. The goal of the NDHCC is to create a centralized data hub, building a searchable repository for NAMs, establishing standards for data reporting and model credibility, developing strategies for interoperability, sustainability, and data reuse, and developing tools for data analytics, dissemination, and sharing. The NDHCC will also serve as the coordinating center for the overall Complement-ARIE program, helping to drive internal program cohesion and fostering community collaborations, including administrative and logistical support while organizing the semi-annual investigators meeting made up of NIH Complement-ARIE award recipients as well as additional support activities.

Is a Plan for Enhancing Diverse Perspectives (PEDP) required?

This Notice of Funding Opportunity (NOFO) does not require a PEDP.

Whom can I reach out to with questions about this announcement?

All questions are welcome. For scientific/research questions, please reach out to Daniel Shaughnessy, [email protected]. For general questions, please reach out to [email protected].

 

What are the key dates in the timeline for planning our application?

What organizations are eligible for this funding opportunity?

• Higher Education Institutions
  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education
• The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
• Nonprofits Other Than Institutions of Higher Education
  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• For-Profit Organizations
  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)
• Local Governments
  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
• Federal Government
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
• Other
  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations

Are foreign organizations eligible?

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

What registrations are required for this funding opportunity?

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information. 

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Who is eligible to be a Program Director/Principal Investigator?

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including individuals from underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

Does this funding opportunity have cost sharing requirements?

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

Are there restrictions of the number of applications submitted to this funding opportunity?

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).
   

How do I request an application package?

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. 

What should the content and form of application submission be?

It is critical that applicants follow the Research (R) Instructions in the How to Apply - Application Guide except where instructed in the notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Are Letters of Intent (LOI) required?

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

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

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

The letter of intent should be sent to:
Daniel Shaughnessy, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Email: [email protected] 

What are the page limitations for my specific aims and research strategy of my application?

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

Please refer to the notice of funding opportunity for additional information on page limits for other sections.

Is a Plan for Enhancing Diverse Perspectives (PEDP) required?

This Notice of Funding Opportunity (NOFO) does not require a PEDP.

Is Cost Share required in the R&R Budget?

Applicants are reminded that although Cost Share is not required; if these types of costs are included in the research application and peer reviewed, it is expected that these costs will not be covered by NIH. Please refer to the notice of funding opportunity for guidance on individual budget elements.

Is a Resource Sharing Plan required?

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide with the following additional instructions. 

• Ensure all project resources, tools, and methods developed through the NDHCC are broadly available (e.g., putting into the public domain) or made accessible to the research community.
• Software tools developed, extended, or otherwise enhanced through this program should be openly disseminated for broad adoption by the relevant communities, following best practices for sharing research software (https://datascience.nih.gov/tools-and-analytics/best-practices-for-sharing-research-software-faq) as well as FAIR (Findable, Accessible, Interoperable, Reusable; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792175/) principles for associated data and documentation.

What if a submission date falls on a weekend or Federal holiday?

When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

How do I submit my application?

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Are mandatory disclosures required?

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].