Translational Centers for Microphysiological Systems (TraCe MPS) is sponsored by National Center for Advancing Translational Sciences (NCATS) / National Institutes of Health (NIH). NCATS has established new centers to strengthen the use of organ-on-a-chip, or tissue chip, technology to develop drugs and potentially reduce the need for animals in research.

Expired RFA-TR-23-001: Translational Centers for Microphysiological Systems (TraCe MPS) (U2C Clinical Trials Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) U.S. Food and Drug Administration ( FDA ) Components of Participating Organizations National Center for Advancing Translational Sciences ( NCATS ) National Cancer Institute ( NCI ) Funding Opportunity Title Translational Centers for Microphysiological Systems (TraCe MPS) (U2C Clinical Trials Not Allowed) U2C Resource-Related Research Multi-Component Projects and Centers Cooperative Agreements NOT-AG-22-043 - Notice of Pre-Application Webinar for RFA-TR-23-001 NOT-OD-22-189 - Implementation Details for the NIH Data Management and Sharing Policy NOT-OD-22-195 - New NIH "FORMS-H" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2023 NOT-OD-22-198 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023 NOT-OD-23-012 - Reminder: FORMS-H Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III.

3. Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this funding opportunity announcement (FOA) is to establish Centers to support research that will accelerate the translational use of Microphysiological Systems (MPS) in drug development through regulatory acceptance and adoption for industrial use, by establishing MPS that are fit-for-purpose for industry needs and have specific defined contexts of use (CoUs) and will be developed with consideration of applicable expectations to achieve regulatory approval.

For this FOA, the term drugs refers to both human pharmacological and biological products unless otherwise specified. These Centers will further the development of MPS as drug development tools (DDTs) that, once qualified, will be made publicly and commercially available to fill unmet needs in drug development.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days before the application due date Renewal / Resubmission / Revision (as allowed) 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.

Required Application Instructions It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description This Funding Opportunity Announcement (FOA) aims to accelerate the translational use of Microphysiological Systems (MPS) in drug development by funding Centers that will establish MPS that are fit-for-purpose for industry needs and have specific defined contexts of use (CoU) and will be developed with consideration of applicable expectations to achieve qualification for regulatory use.

Specifically, the FOA will provide support to establish Translational Centers for MPS (TraCe MPS) that will work towards the regulatory qualification of several MPS platforms as drug development tools (DDTs) that, once qualified, will be made commercially available to fill unmet needs in drug development and in biomedical research.

Under a partnership with the United States Food and Drug Administration (FDA), the NIH will seek input from FDA in order to support this effort with its scientific and regulatory perspective to promote innovations in MPS. More than 90% of the drugs being developed fail due to unpredicted clinical toxicity or lack of efficacy in the clinic.

While current approaches using in vitro 2-D cell assays and/or in vivo animal models during pre-clinical drug development have established value to biomedical research, they also have limitations in being able to reliably predict human physiological responses to various perturbations, contributing to the high attrition rate in drug development.

Microphysiological systems (MPS) hold promise to overcome some of these limitations as one of the New Approach Methodologies (NAMs). The NIH, led by NCATS, developed the MPS or Tissue Chips for Drug Screening program ( https://ncats. nih.

gov/tissuechip ) to address translational problems in drug development through a series of proof-of concept initiatives aimed at use of MPS for 1) improving safety pharmacology studies, 2) developing MPS as disease models for efficacy studies, and 3) paving the way towards precision medicine using MPS to inform clinical studies and trial designs.

The initial MPS program was a five-year partnership among NIH, DARPA and FDA, ( RFA-RM-11-022 and RFA-RM-12-001 ) to support the development and integration of bioengineered multi-organ systems, and the generation of renewable human cell resources for predictive assessment of drug safety and toxicity. MPS disease models ( RFA-TR-16-017 ) established the use of MPS to recreate disease phenotypes and test candidate therapeutics on them.

More recently, RFA-TR-19-014 was aimed towards use of MPS in precision medicine to provide empirical support regarding the intervention's safety and efficacy, and the mechanism that underlies clinical benefit (i.e., evidence that the intervention engages its intended targets and leads to functional improvement, while informing of possible toxicity issues).

The technology development path, including for MPS, is commonly non-linear, and many programs stop at the proof-of-concept stage. A key factor to a linear technology development pathway is to define the value proposition, to promptly transition from an R&D-only stage to the qualification phase, and finally move to optimization and scale-up for rapid adoption.

Challenges, such as device standardization, detailed use cases for MPS to replace or support existing drug discovery assays, costs of implementation, and specialist skills required for model set up may impede the rapid uptake of such technologies.

Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. MPS are an emerging technology that holds the potential to increase translation, efficiency, efficacy, and safety of candidate therapeutics, and potentially become an integral part of the drug development process.

For purposes of this Funding Opportunity Announcement, MPS (otherwise known as tissue chips or organs on chips) are defined as microscale cell culture platform for in vitro modeling of functional features of a specific tissue or organ of human origin by exposing cells to a microenvironment that mimics the physiological aspects important for their function or pathophysiological condition.

MPS design may aim to provide and support cultured cells with physical (e.g., temperature, pH and oxygen), biochemical/electrical/mechanical cues (e.g., flow or stretch), structural/morphological conditions and recapitulate a set of specific properties that define a part of healthy or diseased organ or tissue function.

The adoption of MPS into the drug development process is expected to permit humanized in vitro cell assays that predict human physiology more accurately in situations where species differences are an issue. They may also replace time-consuming and expensive animal experiments, giving patients earlier access to more effective and safer medications.

An integral step in the widespread adoption and industrial use of MPS is its regulatory acceptance by the FDA and other global regulatory agencies. Drug development tools (DDTs) are methods, materials, or measures that can potentially facilitate drug development and may include biomarkers, clinical outcome assessments, and other methods, materials, or measures that aid drug development and regulatory review.

The FDA has developed a Qualification of Drug Development Tools Qualification Program (FD&C Act Section 507), which includes the Biomarker Qualification Program (BQP), Clinical Outcome Assessment, and Animal Model Qualification Program (AMQP). MPS can be considered for biomarker qualification if there is a biomarker output.

In addition, the FDA recently established the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program, which is designed to expand DDT types by encouraging development of DDTs that are outside of the other qualification programs.

Qualification is a conclusion that within the stated context of use, the DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review under the FD&C Act.

Qualification process evaluates the fitness of the model for a specific context-of-use (CoU), with characterization of the challenge agent(s) and exposure, primary and secondary endpoints, triggers for intervention, and key disease values to be replicated for quality assurance and control. Qualification does not encompass the use of a DDT outside the CoU specified through the qualification process.

Once qualified, a DDT may be used within the qualified CoU as part of any relevant drug or biologic Investigational New Drug Application (IND), New Drug Application (NDA) or Biologic Licensing Application (BLA) without submission of additional information to justify the use of the DDT. Qualification of a DDT is voluntary, and the use of a qualified DDT is not required for drug or biologic development.

However, having qualified DDTs that can be used by multiple sponsors helps optimize drug development and evaluation. Increased public availability of qualified DDTs for specific CoUs is anticipated to benefit the public health through (1) increased availability of effective drugs, (2) earlier access to medical therapies and (3) an enhanced knowledge of the drug under development.

Leveraging Existing Research Resources: Applicants are strongly encouraged to leverage existing research resources for their studies whenever possible. The use of MPS platforms that are fairly well-developed and validated for application to a specific context of use is strongly encouraged. The MPS models should consider end-user criteria for biomarkers and assays as defined in a series of publications (https://www.

iqmps. org/publications) for each organ system. Additional resources may include and are not limited to: access to cell banks to source healthy and diseased cells with validated and reliable clinical and genotype information; and established commercial partners for subsequent scale up and commercialization of qualified MPS.

Collaborations among academic researchers, clinicians and/or patient advocacy groups and industry are expected. The Tissue Chip Consortium (The TC Consortium) The NIH Tissue Chip for Drug Screening Program is led and managed by NCATS and utilizes expertise (organ physiology, regulatory science, stem cells, and bioengineering) from various Institutes, Centers and Offices at the NIH and the FDA.

NIH interaction with the non-profit organization the IQ MPS Affiliate ( https://www. iqmps. org/publications ) allows for pharmaceutical companies to work with NCATS staff and Consortium investigators on context of use, marketability and obtaining potential stakeholder/end user feedback.

The Consortium, which consists of these government and industry partners, along with NIH- funded investigators, holds an in-person meeting every 6 months. The Consortium plays a pivotal role in advancing the MPS technology. Award recipients from this FOA will become members of the NCATS-led TC Consortium.

Pre-Application Consultation: Applicants are strongly encouraged to consult with NIH Scientific and Program Staff early in the planning of an application, i.e., more than two months before the application due date (see NIH Program contacts below). This early contact will provide an opportunity to discuss and clarify NIH policies and guidelines, including the scope and goals of the project, and intent of this FOA.

Research Objectives and Scope The goal of this FOA is to establish a network of Translational Centers for Microphysiological Systems (TraCe MPS) that will work in coordination with the NIH and industry, with input from the FDA, towards further development and widespread utilization of MPS for specific context-of-use (CoU) applications necessary for qualification as drug development tools (DDT).

TraCe MPS will be awarded as U2C Centers in order to translate MPS for industrial and regulatory use.

Centers will co-develop study designs for each organ system/MPS model that will be suited to have CoU applications in one or more of the following: 1) safety pharmacology/toxicology, 2) disease modeling and efficacy studies, or 3) precision medicine, each of which could be the basis for qualification as a DDT through the FDA's established regulatory pathways.

Centers funded through the U2C cooperative agreement mechanism will develop and support MPS and biological materials resources that will be made available, upon qualification, to all qualified investigators without regard to the scientific disciplines or disease orientations of their research activities.

In addition to having robust study designs for qualification of MPS platforms, it is expected that sustainability planning includes developing identified avenues for eventual scale up and manufacturing of MPS as DDTs. TraCe MPS will be supported by NCATS and NIH participating institutes and centers over 5 years of award.

These participating agencies are envisioned to take programmatic and scientific stewardship of the Translational Centers. No plans are envisioned for the renewal of these centers after the initial support period.

Overall Organization of TraCe MPS Organization: Each Translational Center will consist of a multidisciplinary research team of investigators with complementary expertise in using MPS platforms for pre-clinical applications and qualification as DDTs.

Utilizing the U2C Cooperative Agreement mechanism, each Translational Center will consist of four components: an Administration Section; an MPS Resources Section; and an MPS Qualification Section and an overall, as described below: The Administration Section will manage and coordinate the Center’s research activities between sections, other program components, and NIH program staff, and will have oversight for integrating all sets of data generated by each of the sections consistently.

The MPS Resources Section will be responsible for ensuring standards, authentication and best practices are followed for resources such as robust and reliable cell sources, MPS hardware, and instrumentation. The MPS Resources Section should ensure that each system considers stated end-user requirements for biomarkers and assays as defined in a series of publications (https://www. iqmps.

org/publications) for each organ system. It will also be responsible for establishing commercial partnerships for subsequent scale up and commercialization of qualified MPS. The MPS Resources Section may also seek collaborations with other academic researchers, clinicians and/or patient advocacy groups and industry as needed for the project.

The MPS Qualification Section will be responsible intaking and assembling data and other documentation required for submitting a qualification package to the FDA (see https://www. fda. gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs ).

The MPS Qualification Section should demonstrate appropriate expertise, facilities and capability to undertake regulatory qualification of MPS. A TraCe MPS Director [Program Director/Principal Investigator (PD/PI)] will be responsible for scientific and administrative oversight of the four components of the Translational Center. The PD/PI (the contact PIs if a multi-PI application) must devote at least 1.

2 person months (10%) of full-time calendar month effort to the program. TraCe MPS Formation and Governance The awards funded under this FOA will be cooperative agreements (see Section VI. 2.

Cooperative Agreement Terms and Conditions of Award). Close interactions among the awardees and NIH, with appropriate interactions with the FDA as facilitated by NIH, will be required to ensure successful execution of the projects proposed with each Translational Center. TraCe MPS Steering Committee: A Scientific Steering Committee will be established post-award and will serve as the operational governing board.

The TraCe MPS Steering Committee will meet virtually every month or in conjunction with semi-annual and annual TC Consortium meetings. It should include: the contact PD(s)/PI(s) for each award, the NIH Program Official for each award, a designated FDA representative, and external scientists (as the need arises).

Key co-investigators and pre- and post-doctoral trainees, in addition to the PD(s)/PI(s), are eligible to attend TraCe MPS Steering Committee meetings. The Steering Committee may establish subcommittees, working groups, etc., to facilitate development, implementation and monitoring of specific functions, functional evaluation, result assessment, collection of information and dissemination of the data.

All projects must be milestone-driven with clear go/no-go criteria. Milestones are deliverables with quantifiable success metrics for each specific aim of the project and include, at the minimum, annual and/or intermediate quantitative criteria with key success metrics specifically defined.

Each TraCe MPS award is expected to have yearly milestones for the overall and for each individual component over the course of the five-year award indicating qualification of at least 4-5 MPS platforms as DDTs, engagement with the NIH and industry partners, and plans for dissemination and/or commercialization of the qualified MPS.

Prior to funding an application, the NCATS Program Official will contact the applicant to discuss the proposed milestones and any changes recommended by peer review and additional feedback from NIH and FDA staff. The NCATS Program Official and the applicant will negotiate and agree on a final set of approved milestones that will be specified in the Notice of Award.

Achievement of the current year milestones as indicated in the annual report will be the basis for evaluating the successful completion and release of funds for the following award year. If justified, future year milestones may be revised based on data and information obtained during the previous year.

If, based on the progress report, the project does not meet any of the the milestones, funding for the project may be discontinued or restricted. Award recipients are expected to share data through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center https://mps. csb.

pitt. edu/. The NIH requires that datasets and associated data will be widely shared with the scientific community for research, while carefully observing established standards.

Award recipients are required to comply with the NIH Data Sharing Policy ( https://grants. nih. gov/grants/policy/data_sharing/ ).

Information is expected to be shared with the TC Consortium, presented at national meetings, and published in the scientific literature.

The research interests and priorities of the participating NIH Institutes/Centers (ICs) include: The National Center for Advancing Translational Sciences (NCATS) is interested in qualification of MPS platforms as DDTs in many areas of drug development that include safety pharmacology assessments that measure drug toxicity, biodistribution and/or pharmacokinetics and pharmacodynamics; in the use of MPS for disease modeling and efficacy studies, such as for clinical studies of rare diseases and/or pediatric patient populations, and other human conditions for which animal models do not exist or are hard to generate; and in the use of MPS in precision medicine that will address issues of pharmacokinetic variability or difficulties of setting pharmacodynamic endpoints for patient populations.

NCATS intends to commit $4M per year to fund 2-4 awards. Budget requests can be from $500,000 to $1,000,000 direct costs per year and must be strongly justified, including additional MPS platforms to be qualified.

Research interests and priorities of NCI: The National Cancer Institute (NCI) is interested in qualification of MPS platforms as DDTs for cancer therapeutic agents to be used in studies that include efficacy, toxicity and off-target effects of anti-cancer agents; that elucidate mechanisms of action and drug resistance to cancer therapeutic agents; studies of treatments/agents that may decrease or reverse adverse cancer therapy effects or sensitize tumors to specific treatments; and agents that alter the relationship between the tumor and its host by modifying the host’s biological response to tumor cells with resultant therapeutic benefits.

For MPS platforms that employ tumor cells, the DDTs can be qualified for tumors at primary and/or metastatic sites. Research interests and priorities of NIA: The National Institute on Aging (NIA) is interested in the development of Microphysiological Systems (MPS) as tools to advance precision medicine for Alzheimer’s disease (AD) and Alzheimer’s disease Related Dementias (ADRD) Treatment and Prevention.

The development of MPS platforms that precisely model AD/ADRD will require overcoming several technical and regulatory challenges including engineering platforms that: 1) recapitulate the complexity of the human brain; 2) recreate the neurodegenerative microenvironment, 3) reflect the heterogeneity and complexity of the disease; 4) accurately predict therapy efficacy and safety in humans; 5) follow rigorous and reproducible standards; and 6) achieve regulatory approval as qualified Drug Development Tools.

Applicants are encouraged to align the MPS platforms with the human multi-omic data from NIA’s Accelerating Medicines Partnership-Alzheimer’s Disease Program (AMP-AD). The AMP-AD Program supports integrated analyses of large-scale AD/ADRD molecular data with network modeling approaches and experimental validation.

All data, including biological data and analytical methodology, are publicly available through the centralized big data infrastructure AD Knowledge Portal . NIA intends to commit $3. 5M in FY24 to fund 2 awards.

Budget requests can be up to $1,000,000 direct costs per year and must be strongly justified, including additional MPS platforms to be qualified. Non-Responsive Applications The following types of research activities are outside the scope of this FOA and will be considered non-responsive. (Non-responsive applications will not be reviewed.)

: Projects that propose to use MPS platforms that have not been well validated Projects that propose the use of MPS platforms without clearly defined specific context of use Note: NIH will hold a pre-application technical assistance webinar for this FOA. When published, the related Notice will be linked with the FOA. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this FOA.

Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA. Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards RFA with multiple ICs/components (choice 2, not preferred; use if ICs/components are not showing each contribution in the FOA) The aggregate amount shown below must reflect the contribution of all participating ICs/components.

A document or MOU must be attached in SharePoint that specifies the contribution for each IC/component. Issuing IC and partner components intend to commit an estimated total of $12 M per year to fund 5-8 awards. Award Budget requests are based on IC specific limitations provided above.

The scope of the proposed project should determine the project period. The maximum project period is 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III.

Eligibility Information 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are not allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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. Program Directors/Principal Investigators (PD(s)/PI(s)) 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.

Eligible Individuals (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 his/her organization to develop an application for support.

Individuals from diverse backgrounds, including 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 .

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 SF424 (R&R) Application Guide. The PD/PI (the contact PIs if a multi-PI application) must devote at least 1. 2 person months (10%) of full-time calendar month effort to the program.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3. Additional Information on Eligibility 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 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 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide , except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants. gov downloadable forms currently used with most NIH opportunities.

Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Component Type for Submission MPS Qualifications Section The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

When preparing your application, use Component Type Overall . All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted. SF424(R&R) Cover (Overall) PHS 398 Cover Page Supplement (Overall) Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall) Follow standard instructions. Milestone Plan: The filename "Milestone Plan. pdf" should be used.

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. Include specific go/no-go criteria (e.

g yearly) upon which project progress will be assessed for continued funding. Provide a graphical display summarizing the milestones plan in the form of a Gantt Chart.