DARPA-PA-26-09.pdf

DARPA-PA-26-09

Program Announcement (PA) Resuscitation and Prevention of Ischemia-

Induced Dysfunction (RAPIID) Task Area-3: Regulatory Advancement and

Program Infrastructure Biological Technologies Office

July 2, 2026

OVERVIEW INFORMATION

Federal Agency Name: Defense Advanced Research Projects Agency (DARPA), Biological Technologies Office (BTO)

Funding Opportunity Title: Resuscitation and Prevention of Ischemia-Induced Dysfunction (RAPIID) Task Area-3: Regulatory Advancement and Program Infrastructure

Announcement Type: Program Announcement (PA)

Funding Opportunity Number: DARPA-PA-26-09

Assistance Listing Number: Not applicable

Dates/Time: All Times are Eastern Time Zone (ET) o Posting Date: July 2, 2026 o Questions Due Date: July 10, 2026 at 3:00 p.m. ET o Proposal Due Date: July 29, 2026 at 3:00 p.m. ET

Anticipated Individual Awards: The Government anticipates funding one award.

Types of Instruments That May Be Awarded: Other Transactions for Research under 10 U.S.C. § 4021

NAICS Code: 541715

Agency Contact:

The PA Coordinator for this effort may be reached at: RAPIID@darpa.mil

DARPA/BTO

ATTN: DARPA-PA-26-09

675 North Randolph Street Arlington, VA 22203-2114 mailto:RAPIID@darpa.mil

PROGRAM ANNOUNCEMENT (PA)

DARPA-PA-26-09

Resuscitation and Prevention of Ischemia-Induced Dysfunction (RAPIID) Task Area-3: Regulatory Advancement and Program Infrastructure

Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO)

SECTION I: RAPIID PROGRAM DESCRIPTION

Primary challenges with translating technological advancements from the laboratory to real-world usage include a lack of investment to ensure manufacturing scalability, and usability, as well as clinical, regulatory, and commercialization preparedness. Previous investments by DARPA to address potential blood shortages in austere, pre-hospital settings (i.e., the Fieldable Solutions for Hemorrhage with bio-Artificial Resuscitation Products (FSHARP) program) have derisked scalable, shelf-stable components that would provide the resuscitative functions of whole blood (i.e., oxygen delivery, hemostasis, and volume expansion) when used together. However, bringing those components through clinical studies and regulatory approval as well as the development of enabling technologies and guidance to facilitate their use outside of the laboratory were out-of-scope in previous DARPA efforts. RAPIID is designed to bridge the gap between the proof-of-concept achievements of the FSHARP program and actual clinical use by the military and civilians.

With FSHARP demonstrating that shelf-stable blood products can be created, DARPA is now taking on the next challenge: delivering a complete, deployable, and authorized system that can save lives in the field. To achieve this goal, RAPIID will focus on pushing high technology readiness level (TRL)/medical readiness level (MRL) capabilities through the regulatory process by funding studies to demonstrate safety and efficacy of blood analog components and their ability to work in combination; manufacturing scalability of individual blood analog components; and developing and scaling associated fielding technologies.

The Task Area 3 (TA-3) performer must demonstrate the full suite of Contract Research Organization (CRO)/Academic Research Organization (ARO) capabilities, including trauma trial sponsorship (with Exception from Informed Consent (EFIC) experience), regulatory submission and sponsorship (IND/IDE), Good Laboratory Practice (GLP) large-animal model execution, clinical trial execution, data management, statistical oversight, and direct engagement with military and civilian trauma care leadership. These key activities are central to the TA-3 mission.

To ensure regulatory credibility and rapid operational advancement, the TA-3 performer must provide a single, unified point of accountability for the entire clinical and regulatory lifecycle of the RAPIID blood analog system. The prime performer must maintain direct operational oversight and technical leadership over key program areas, including trauma trial sponsorship (with EFIC experience), regulatory submissions, GLP large-animal testing, clinical trials, data management, and military/civilian trauma care outreach. Proposals must show how the lead entity will maintain direct, continuous control over all technical and regulatory deliverables, ensuring that distributed workflows do not introduce programmatic delay or regulatory risk.

This integrated, independent approach is critical for ensuring unified accountability, regulatory credibility, and the timely, risk-mitigated, and accelerated advancement of the RAPIID blood analog system from laboratory to fielded solution.

1.1 PROGRAM DESCRIPTION

The RAPIID program seeks to build on the success of the FSHARP program’s core finding that a whole blood-like product can be generated with shelf-stable, bio-synthetic components while increasing the focus on transition, clinical trials, and regulatory approval (Figure 1).

Figure 1. Vision for the RAPIID Program, including how it connects to the FSHARP Program.

Key to RAPIID’s success, in addition to accelerating the development of potential blood analog components through early human clinical trials, is the development of technologies to support administration in the field (e.g., ruggedized packaging, point-of-care diagnostics to inform transfusion decisions and follow-on care), development of technologies for manufacturing scale-up, clinical practice guideline (CPG) development, regulatory strategies that adequately prepare products for use in humans (e.g., via Emergency Use Authorization (EUA) or full approval), and commercial strategies that will enable the products to be available for purchase and produced in quantities to support market demand. The goal is to enable usage of the blood analog components as early as fiscal year (FY) 2029.

1.2 PROGRAM STRUCTURE AND SCHEDULE

The RAPIID program is designed to be completed in two phases across 36 months:

RAPIID Phase 1 (months 1-12, total of 12 months) – RAPIID Performers will develop blood analog components and auxiliary fielding technologies, and demonstrate their safety and efficacy. Evaluations for blood analog components will include pre-clinical in vivo models of traumatic hemorrhage and studies to support FDA regulatory filings (e.g., Investigational New Drug (IND), Investigational Device Exemption (IDE)). In addition, performers must demonstrate scalable Good Manufacturing Practice (GMP)-ready manufacturing and coordinate across TAs (see Figure 2/Sections 1.3 and 1.4) to develop clinical trial, regulatory, and commercialization plans. For TA-3, this announcement requires the proposer to execute the full scope of both Phase 1 and Phase 2 TA-3 activities, with continuity across the program.

RAPIID Phase 2 (months 13-36, total of 24 months) – Performers will coordinate across

TAs to further validate the blood analog system (BAS) for trauma/hemorrhage indications in early-stage, human clinical trials. In parallel, performers will demonstrate GMP-compliant manufacturing scale-up to ensure the system is ready for fielding and coordinate across TAs to finalize commercialization and manufacturing strategies.

The RAPIID program will include four TAs:

TA-1: Individual Blood Analog Components*** TA-2: Blood Analog System (BAS) Fielding Technologies*** TA-3: Regulatory Advancement & Program Infrastructure TA-4: Commercialization & Sustainment***

***Please note that this PA requests proposals addressing ONLY TA-3. Information about TA-1, TA-2, and TA-4 within this PA is provided to inform TA-3 proposers about the purpose of cross-TA interactions throughout the program. The TA-3 performer is expected to work with the performer(s) in TA-1 and/or TA-2 to ensure success of the program. Failure to participate in required coordination activities may affect continued program participation and may result in corrective action, up to and including termination, in accordance with the terms and conditions of the award. See Section 1.9 for more information.

1.3 RAPIID TECHNICAL OBJECTIVES AND TASK AREAS (TA-1, TA-2)

Task Area 1 (TA-1): Individual Blood Analog Component Development In TA-1, performers will focus on stand-alone development of shelf-stable components for the blood analog:

Oxygen carrier Platelet-derived products, shelf-stable platelets, or platelet-like particles Dried plasma

Early in RAPIID, each TA-1 performer will demonstrate safety, efficacy, and shelf-stability of their design-locked product in functional tests and pre-clinical models with the goal of generating the evidence needed to submit a regulatory package to the FDA to enable clinical trials in the anticipated RAPIID Phase 2 and, ultimately, a request for an EUA or full licensure for a trauma/hemorrhage indication. Performers must also demonstrate GMP readiness as part of selection, including process validation approach, prospective lot-release specifications, identified critical suppliers and qualification criteria, and stability data sufficient for operational conditions;

manufacturability at scale will be weighed alongside safety and performance. Anticipated clinical studies will be conducted by testing and evaluation (T&E) partners in TA-3 with pre-specified clinical and operational endpoints that enable rapid decision making for each blood analog component candidate.

Task Area 2 (TA-2): BAS Fielding Technologies Development TA-2 focuses on the delivery format designed for far-forward use in combat and on the point-of-care diagnostics to support decision-making regarding blood analog usage. This includes compatibility testing between bags, warmers, and other packaging as well as ruggedization to withstand combat stressors such as vibration, shock, and altitude depressurization. Relevant point-of-care diagnostics designed to inform transfusion decisions at role 1 and higher levels of care will be focusing on the detection of blood analog components, or the analysis of effects of blood analog products on coagulation, to name a few. These solutions must demonstrate clinical validation as a https://sam.gov/workspace/contract/opp/13dca662b7da444593550da9d021d533/view https://sam.gov/workspace/contract/opp/61a78b0d91244a65b239a1248a80e7af/view companion diagnostic within the TA-3 clinical testing plan and be developed to fit distributed operational and logistical constraints. Operational assessments and user validation will drive updates to techniques, tactics, procedures, sustainment plans, and procurement actions.

Proposals to address TA-1 and TA-2 were solicited under a separate Program Solicitation, which can be accessed at DARPA-PS-26-124, to develop individual blood analog components (TA-1) and point-of-care diagnostic systems (TA-2). The solicitation closed on June 24, 2026 but the information remains available on SAM.gov.

This announcement specifically solicits proposals only for Task Area 3 (TA-3) of the RAPIID program. In addition to the technical objectives described for TA-1 and TA-2, RAPIID will support the development of a program transition strategy, including clinical, regulatory, and commercialization pathways to ensure availability and adoption of the individual blood analog components, the complete blood analog system, and associated fielding technologies beyond the DARPA effort. This development will be primarily addressed by TA-3 and TA-4. It is expected that performers in TA-3 and TA-4 will coordinate with performers in TA-1 and TA-2.

To accelerate this transition and reduce risk, RAPIID is investing in a dedicated, independent research and regulatory partner akin to a CRO or Academic CRO in the drug development world.

By placing this function on contract, RAPIID ensures that clinical trials, regulatory submissions, and commercialization activities are managed efficiently, with unified accountability and operational rigor. This approach enables parallel development and commercialization efforts, streamlines coordination across technical areas, and maximizes the likelihood that innovative blood analog solutions will move smoothly from the preclinical research phase to real-world deployment and market adoption.

Task Area 3 (TA-3): Regulatory Advancement & Program Infrastructure The RAPIID program requires a dedicated, independent research and regulatory function to ensure that blood analog components and fielding technologies developed under TA-1 and TA-2 are rigorously evaluated and advanced toward clinical adoption. Task Area 3 (TA-3) serves as the program’s CRO, providing unified, in-house capabilities and accountability for all regulatory, clinical, and preclinical activities.

TA-3 is responsible for integrating and executing activities necessary to transition the RAPIID system from laboratory innovation to authorized, field-ready solutions. This includes:

Preclinical Evaluation: Conducting combination testing of blood analog components to confirm safety and efficacy when administered together, utilizing both in vitro testing and in vivo GLP-compliant large-animal models. These studies are designed and executed independently from TA-1 and TA-2 development teams to ensure unbiased assessment and regulatory acceptability.

Regulatory Sponsorship: Acting as the Sponsor of Record for all Investigational New Drug (IND), Investigational Device Exemption (IDE), and other regulatory document submissions to the U.S. Food and Drug Administration (FDA) related to clinical trial activities, providing a unified and accountable regulatory strategy.

Clinical Trial Design and Execution: Designing, sponsoring, and conducting multi-site Phase I and Phase II clinical trials, which may include EFIC, to generate the evidence required for regulatory approval and clinical adoption.

Data Integrity and Program Management: Maintaining responsibility for all regulatory, clinical, and data management activities, ensuring consistency, data integrity, and programmatic continuity throughout the program.

Peer-Reviewed Dissemination: Publishing results from completed trials in peer-reviewed journals to support regulatory submissions and inform the broader trauma care community.

CPG Development: Engaging directly with the Joint Trauma System (JTS), Committee on Tactical Combat Casualty Care (CoTCCC), and Service medical leadership to translate trial results into actionable CPGs for rapid doctrinal adoption.

The TA-3 performer must demonstrate the full suite of CRO/ARO capabilities in-house, including trauma trial sponsorship (with EFIC experience), regulatory submission and sponsorship, GLP large-animal model execution, clinical trial execution, data management, statistical oversight, and direct engagement with military and civilian trauma care leadership. These key activities are central to the TA-3 mission and are expected to be performed internally, rather than distributed across a consortium or fully subcontracted out. This integrated, independent approach is critical for ensuring unified accountability, regulatory credibility, and the timely, risk-mitigated advancement of the RAPIID blood analog system from laboratory to fielded solution.

Table 1. Comparison of TA-1/2 Performer Activities to TA-3 Performer Activities.

✓*-for TA-3 under "Preclinical Testing (Individual)" indicates limited/GLP studies as needed for regulatory efficiency.

Activity / Responsibility Description

TA-1/2

Performer

TA-3

Performer

Component/Device Development

Develop individual blood analog components and fielding technologies/devices

Preclinical Testing (Individual)

Conduct in vitro and in vivo studies for individual components/devices ✓ ✓*

Preclinical Testing (Combination/System)

Evaluate safety/efficacy of components/devices in combination (system-level, GLP as needed)

Regulatory Engagement (Individual)

Prepare and submit IND/IDE packages for individual products; engage with FDA ✓ ✓

Regulatory Engagement (System)

Prepare and submit IND/IDE/EUA for integrated system; act as Sponsor of Record

Manufacturing Readiness Demonstrate scalable, GMP-ready manufacturing; assess readiness for transition

Clinical Trial Planning Provide data/input for trial planning; TA-3 leads design and operational planning for efficient multisite trials

Clinical Trial Execution Provide materials/data as needed; TA-3 sponsors and executes multi-site, efficient clinical trials

Data Sharing & Coordination

Share validation data/results; coordinate across TAs ✓ ✓

CPG Development Provide input/data for clinical practice guidelines ✓

Peer-Reviewed Publication Publish results from studies and trials ✓

Task Area 4 (TA-4): Commercialization & Sustainment For the RAPIID commercialization strategy, the objectives include:

Generation of a comprehensive Business plan to include satisfying capital needs and capturing the well-defined and well-supported market opportunity;

Generation of a plan for the Government to procure the solutions at scale and within timeframe;

Generation of a scalability strategy to ensure sufficient manufacturing; and Identification of an approach to ensure blood analog components are licensed for use in combination outside of the research, development, testing and evaluation (RDT&E) activities of the program.

TA-4 performer(s) will conduct market research and analysis to help prepare TA-1 and TA-2 performers to be commercially viable after the program ends. TA-1 and TA-2 performers will be evaluated on supply-chain resilience and must work with TA-4 performers to propose credible pricing and procurement strategies. Early market work conducted by TA-4 performers will define pricing, procurement pathways, and dual-use (i.e., military and civilian) demand so that the best candidates can cross from selection to sustained adoption without delay. TA-4 performers will help connect TA-1 and TA-2 performers with potential commercialization and manufacturing partners. The DARPA team will coordinate with Government organizations to identify and mitigate industrial risk, develop guaranteed-purchase agreements, and assess the secondary market demands from civilian trauma care, disaster response, and austere medicine for TA-1 and TA-2 products.

A request for abstracts to address TA-4 was announced under a separate Special Notice, DARPA- SN-26-91. The abstract submission deadline closed on June 29, 2026, but the Special Notice will remain available on SAM.gov.

DETAILED RAPIID TA-3 INFORMATION

1.4 ACQUISITION STRATEGY

Proposers will submit a full proposal to address TA-3 activities in both RAPIID Phase 1 (base) and RAPIID Phase 2 (option) in accordance with the instructions in this PA. Please note that RAPIID Phase 2 is contingent on program funding and information is subject to change. The Government will review conforming proposals, and proposers may be selected for the negotiation of an award of an Other Transaction (OT) for Research agreement.

1.5 PROGRAM ANNOUNCEMENT SCOPE

Proposals submitted in response to this PA must address ONLY TA-3. Organizations and/or individuals that are awarded funding to conduct work under TA-3 are not eligible to receive awards/funding to conduct work under TA-1 and/or TA-2. Proposals submitted to this PA that aim to carry out the functions of other TAs in addition to TA-3 will be considered non-conforming and rejected without review.

Please review Table 2 for a summary of TA combinations that are acceptable for proposing organizations and/or individuals. TA-3 is highlighted in yellow.

https://sam.gov/workspace/contract/opp/61a78b0d91244a65b239a1248a80e7af/view

Table 2. Compliance Table for Potential RAPIID Proposers

If you are awarded funds under…

TA-1: Oxygen Carrier

TA-1: Platelet-like Particle/ Platelet Derived Component

TA-1: Plasma TA-2: Point-of- Care Device

TA-3: Regulatory Advancement & Program Infrastructure

TA-4:

Commercialization & Sustainment

TA-1 Oxygen Carrier

Yes, separate proposals

Yes, separate proposals;

Yes, required, same proposal

No No

TA-1: Platelet-like Particle/ Platelet Derived Component

Yes, separate proposals

Yes, separate proposals

Yes, required, same proposal

No No

TA-1: Plasma Yes, separate proposals

Yes, separate proposals

Yes, separate proposals; not required

No No

TA-2: Point-of- Care Device

Yes, required, in same proposal

Yes, required, same proposal

Yes, separate proposals; not required

No No

TA-3: Regulatory Advancement & Program Infrastructure

No No No No Yes, separate proposal

C an y ou b e aw ar de d fu nd s u nd er

TA-4:

Commercialization & Sustainment

No No No No Yes, separate proposal

1.5.1 TA-3 Scope and Regulatory Objectives

The research objective of TA-3 is to secure regulatory authorization/licensure by FDA by the end of the program through the execution of advanced research into components from TA-1 and TA-

2. TA-3 will facilitate GLP-studies that support regulatory submissions, coordinate with TA-1 and TA-2 performers to develop clinical trial plans, draft CPGs informed by the results of testing to facilitate usage of BAS and execute clinical trials during Phase 2.

TA-3 research will assess TA-1 components and TA-2 devices against the metrics described in Section 1.7.2/Table 3 and Section 1.7.3/Table 4 to determine if they are meeting or exceeding program expectations. TA-3 will also research and evaluate combinations of blood analog components to determine the best candidates to provide all resuscitative functions of whole blood when administered sequentially.

1.5.2 Out of Scope

Please note that proposals including the following are considered out-of-scope for TA-3:

Development of blood analog components or devices addressing TA-1 and/or TA-2 goals (these were separately solicited for under DARPA-PS-26-124)

Executing research on and testing of components and devices not developed as part of

RAPIID

Executing research on and testing for only TA-1 components or only TA-2 devices under

DARPA-PS-26-124

1.5.3 Non-Conforming

Please note that proposals including the following are considered non-conforming and will be removed from consideration:

Proposals that only address 1 Phase.

Proposals that do not comply with Section 2.6.4.

1.6 METRICS, MILESTONES, AND DELIVERABLES

Progress toward program goals will be determined using metrics (quantitative target specifications of the technology to be developed), milestones (significant technical and reporting accomplishments), and deliverables (tangible technical and reporting products).

A schedule of milestones, deliverables, and payments is included as Attachment F. Proposers are expected to define and include in Attachment F their own additional milestones and deliverables, as needed, based on their specific approaches to achieving the objectives of the RAPIID program.

Additional proposed milestones may or may not be incorporated into the final award.

Various metrics and milestones will require performers to coordinate with or provide components/devices to performers supporting other TAs. This coordination will be facilitated by Associate Performer Agreements (APAs), as described in Section 1.9.

1.6.1 RAPIID Meetings and Reporting Deliverables

RAPIID performers will be expected to participate in regular meetings with DARPA, the Government team, and other performers throughout the program. Meeting and reporting milestones are to include rigorous analysis and critical evaluation of results and progress.

RAPIID Phase 1 Kick-off Meeting: Performers are expected to participate in a kick-off meeting at the beginning of the RAPIID program. This meeting may be held with individual or all performer teams, to be determined by DARPA. Deliverables will be presentations that describe the project work plan, anticipated challenges, and risk mitigation strategies.

Monthly Reports: Performers are expected to meet monthly with the DARPA and Government teams to review their progress toward the goals of the RAPIID program.

Deliverables will be a monthly briefing describing efforts and a monthly financial report for project expenditures and spend plan.

Annual Reports: At the end of each year the performers are expected to provide a written technical report describing the work completed within the reporting period toward the tasks, key results and findings, and risks encountered and mitigations taken.

Annual Meetings: Performers are required to participate in annual meetings (3 total over the 36-month program) to provide scientific and technical updates to the DARPA program management team, relevant Government stakeholders, and other performers in the RAPIID program. Deliverables will be presentations that describe progress towards the milestones and scientific goals and summarize outstanding challenges and mitigations.

Site Visits: Performers should plan to host the DARPA and Government teams at least once annually for a site visit to their laboratories and research facilities. Estimated timing for the first visit will be Month 6 but is subject to change. These site visits may coincide with Milestones and Deliverables described in Sections 1.7.2 and 1.7.3. The TA-3 performer may be requested to participate in other performer site visits in a virtual capacity at the discretion of the DARPA team.

Final Report: At the conclusion of the project, the performers are required to provide a written technical report describing the completed technical and transition efforts, key results and findings, challenges and limitations to the project, and potential next steps. This will be in lieu of the Annual Report.

1.6.2 TA-3, RAPIID Phase 1 (Base, Months 1-12)

In RAPIID Phase 1, TA-3 performers will execute GLP-compliant preclinical research on combinations of TA-1 components in in vitro studies and in vivo models to identify leading candidates for the blood analog and to support regulatory packages (Table 3). These studies will complement the non-GLP, pre-clinical testing performed by TA-1 performers to demonstrate safety and efficacy of their components.

Metrics Table 3. Metrics for TA-3, RAPIID Phase 1

TA-3 Domain TA-3, RAPIID Phase 1 Metrics

Blood Analog Safety & Efficacy (Combination of TA-1 components) *completed in coordination with TA-1 performer(s)

Month 6:

• In in vitro studies and/or in vivo models of hemorrhage, demonstrate safety and efficacy within 20% margin of whole blood performance

• Demonstrate a <10% decrease in performance of each individual component when used in combination to make a whole blood analog

Month 9:

• In in vitro studies and/or in vivo models of hemorrhage, demonstrate safety and efficacy within 10% margin of whole blood performance

• Complete initial absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetics (PK) studies for combinations of components

• Demonstrate no interactions with commonly deployed countermeasures (e.g., TXA, ketamine) resulting in ≥10% decrease in performance

Month 12:

• Demonstrate non-toxicity and pharmacological safety via IND-enabling assessments

Milestones and Deliverables

Month 1: Initial Animal Subjects Research Protocol/Human Subjects Research Protocol Submissions. If animal and/or human subjects research is expected prior to IND-enabling studies, performers must submit animal subjects research protocols to the DHA Animal Care and Use Review Office (ACURO) and/or human subjects research protocols to the DHA Office of Human Research Oversight (OHRO) within 30 days after award. Performers will provide documented confirmation of submission to DARPA.

Month 3: Animal study protocol(s) approval from ACURO and/or OHRO. Performers will provide documented confirmation that the ACURO and/or OHRO has approved animal study protocol(s) to test and validate components in vivo. If approval has not been received, performers will provide a documented justification, estimated timeline for approval, and risk mitigation plan.

Month 3: Cybersecurity Maturity Model Certification (CMMC) Level 2. Performers must provide documented confirmation that they have achieved CMMC Level 2 certification and are registered in the DoD's Supplier Performance Risk System (SPRS).

Performers cannot be able to handle Controlled Unclassified Information (CUI), including Personally Identifiable Information (PII) and Protected Health Information (PHI) until this certification is completed. Please see the related bullet in SECTION VI: Special Considerations for more information.

Month 5: Execute coordination plan with TA-1 and/or TA-2 performers. The TA-3 performer will provide documented agreement with the coordination plan generated by the TA-1 and/or TA-2 performer(s) to ensure clear communication to support regulatory and preclinical/clinical trial research tasks.

Month 5: GLP IND-enabling studies plan. Performers must detail plans to execute IND-enabling studies, including documented commitment from TA-1 performers for manufacturing sufficient quantities of their product at the required quality.

Month 6: Demonstration of combination non-inferiority to stored whole blood within 20% margin with ≤10% decrease in individual component performance. Using in vitro studies and in vivo models of hemorrhage and shock, performers must identify at least one combination of TA-1 blood analog components that demonstrates non-inferiority to stored whole blood within 20% margin. In addition, the performance of the components in combination will be compared to their performance alone to ensure co-administration will not significantly degrade performance. Performers are free to determine what attributes best demonstrate non-inferiority but must provide justification for their decisions, including relevance for FDA licensure.

Month 6: Initial engagement with Joint Trauma System and relevant civilian organizations for drafting CPGs. Performers will meet with organizations responsible for approving military and publishing civilian CPGs to obtain feedback on a preliminary plan to develop CPGs for the blood analog system, including recommendations on the composition of the drafting committee, CPG scope, evidence review method, etc.

Month 9: Demonstration of combination non-inferiority to stored whole blood within 10% margin with ≤10% decrease in individual component performance. Using in vitro and in vivo models of hemorrhage and shock, performers will demonstrate non-inferiority to stored whole blood within 10%.

Month 9: Half of IND-enabling studies completed, including initial ADME and PK studies complete. Using models relevant for regulatory acceptability, performers must execute and provide results from GLP-studies that would support the request for an EUA or regulatory licensure for the blood analog.

Month 10: Clinical Trial Plan. Performers will submit for review the clinical trial plan for evaluating safety and efficacy of the blood analog system.

Month 12: IND-enabling assessments complete for blood analog with TA-1 components, and IND submission. Performers will compile results from IND-enabling non-toxicity and pharmacological safety testing of the blood analog and submit an IND package to FDA for review.

Government Furnished Information, Materials, and/or Equipment

Month 4: Blood analog components from TA-1 for combination testing.

Month 7: Design-locked blood analog components for testing. By Month 6, TA-1 performers are expected to design-lock their blood analog components. These versions are expected to be used for testing for the remainder of the program.

1.6.3 TA-3, RAPIID Phase 2 (Priced Option, Months 13-36)

In Phase 2, TA-3 performers will support the execution of clinical trials for TA-1 individual blood analog components and the whole blood analog and required testing for TA-2 devices.

Decisions to progress RAPIID TA-3 Phase 2 will be informed by RAPIID Phase I TA-1 and TA- 2, RAPIID Phase 1 TA-3 metrics and milestones, ability to achieve FDA approval to proceed with clinical trials, and the availability of funds.

The metrics information in Table 4 regarding RAPIID TA-3 Phase 2 may change dependent on the RAPIID Phase 1 of TA-1, TA-2, TA-3 results.

Metrics Table 4. Metrics for TA-3, RAPIID Phase 2

TA-3 Domain TA-3, RAPIID Phase 2 Metrics

Blood Analog Safety & Efficacy (Combination of TA-1 components) *completed in coordination with TA-1 performer(s)

Month 20:

• Demonstrate non-inferiority to stored whole blood safety in Phase I clinical trial

Month 32:

• Demonstrate non-inferiority to stored whole blood safety & efficacy in Phase II clinical trial

Point-of-Care Diagnostics/Devices *completed in coordination with TA-2 performer(s)

Month 32:

• Demonstrate clinical validity in validation study (if required)

For TA-1, performers must demonstrate their products are non-inferior in clinical trials and can be produced in a GMP-compliant manner at a high rate. TA-1 performers selected for Phase 2 will provide GMP product to TA-3 performer for the clinical trial.

Deliverables and milestones for TA-3 for Phase 2 include:

TA-3 Phase 2 Collaborations with TA-1 Blood Analog Components

Month 13: IND Approved by FDA and Clinical Trial Protocol Submitted to the Institutional Review Board (IRB). The TA-3 performer will submit the clinical protocol for testing the blood analog with TA-1 components to the IRB and provided documented confirmation of submission to DARPA. Following IRB approval, the clinical trial protocol will be submitted to the OHRO.

Month 14: Initiate Phase I Clinical Trial for Blood Analog and Components. The TA- 3 performer will execute the clinical trial according to the plan developed in coordination with TA-1 performers and provided documented confirmation of initiation to DARPA. If there are any delays, the TA-3 performer must provide a risk mitigation plan.

Month 24: Phase I Clinical Trial for Blood Analog and Components Complete. The TA-3 performer will provide a report regarding the results of safety testing for individual components and component combinations.

Month 25: Initiate Phase II Clinical Trial for Blood Analog and Components. The Phase II trial should start immediately after completion of the Phase I safety trial, provided there were no issues during Phase I. If there are any delays, the TA-3 performer must provide a risk mitigation plan.

Month 36: Phase II Clinical Trial for Blood Analog and Components Complete. The TA-3 performer will provide a final report detailing the results of the Phase II individual components and component combinations, including demonstrate non-inferiority to standard care.

TA-3 Phase 2 Collaborations with TA-2 Point-of-Care Diagnostics/Devices TA-2 performers will align on a regulatory pathway with FDA by Month 16. The following will only apply if diagnostic/device validation is deemed necessary.

Month 17: Diagnostic/Device Validation Plan. The TA-3 performer will provide documented confirmation of the agreement to the diagnostic/device validation plan developed in coordination with TA-2 performers.

Month 20: Initiate Diagnostic/Device Validation for TA-2 devices (if necessary). The TA-3 performer will execute the validation plan developed in coordination with TA-2 performers.

Month 32: Diagnostic/Device Validation Complete. The TA-3 performer will provide a report regarding the results of the validation study, including assessment of whether the technology functions as intended to support the fielding of the blood analog (e.g., correlation with clinical outcomes, clinical utility, and/or analytical performance).

Clinical Practice Guidelines (CPGs)

Month 24: Draft CPGs. Performers will submit a draft version of the CPGs for Government review.

Month 36: Finalized CPGs. Performers will submit a final version of the CPGs for Government review.

Government Furnished Information, Materials, and/or Equipment

Month 13: Blood analog components from TA-1 to support Phase I clinical trials.

Month 19: TA-2 devices to support clinical evaluation.

Month 24: Blood analog components from TA-1 to support Phase II clinical trials.

1.7 GOVERNMENT TEAM AND INDEPENDENT VALIDATION AND

VERIFICATION (IV&V)

In support of the RAPIID technical and transition efforts, DARPA will utilize Government IV&V teams and subject matter experts (SMEs) to assess and provide feedback on technical, regulatory, and commercialization aspects of the projects. The RAPIID Government-led IV&V efforts will primarily be to provide independent assessments of the TA-1 components and TA-2 devices as well as offering SME insights regarding appropriate animal models for trauma and hemorrhage indications in coordination with TA-3 research efforts. In addition to in vitro IV&V testing, TA-1 components will be evaluated in a large animal model near the end of Phase 1. These evaluations will be performed by the IV&V team at an IV&V-managed site with close coordination and in conjunction with the TA-3 performer. The TA-3 performer will provide the IV&V team standard operating procedures (SOPs), data, and other relevant information for sequentially administering combination components.

1.8 CROSS-TA INTERACTIONS, COLLABORATION, AND DATA AND

MATERIALS SHARING

Collaboration across TAs is required to meet the RAPIID program goals. Performers will be required to interact and collaborate across TAs as summarized in Figure 2. TA-1 and TA-2 performers will engage regularly with TA-3 to facilitate testing of blood analog components and devices and coordinate clinical testing planning. TA-4 will coordinate with TA-1 and TA-2 to develop commercialization and manufacturing plans.

Figure 2. Anticipated data/information flow between TAs for the RAPIID program.

To facilitate collaboration as summarized in Figure 2, performers will enter into an Associate Performer Agreement (APA; part of Attachment D) with other select RAPIID performers. The APA will include the basis for sharing information, data, technical knowledge, expertise and/or resources essential to the integration of the program TAs and components. This APA will ensure appropriate coordination and integration of work by program contractors, ensure complete compatibility between data, tools and services, and prevent unnecessary duplication of efforts and maximize commonality. TA-1 and TA-2 performers will be expected to enter into APAs with all other RAPIID performers except those in direct competition with each other (i.e., oxygen carrier performers will not enter into APAs with other oxygen carrier performers). Awardees must provide timely support and participate in the development, negotiation, and execution of any required APAs. The Government expects required APAs to be completed within three months of award unless an extension is approved by the Government. Failure to make reasonable, good-faith efforts to complete required APAs, or failure to comply with Government-directed APA requirements, may result in corrective action, up to and including termination, in accordance with the terms and conditions of the award.

Additionally, RAPIID will require that performer data and analysis be shared with DARPA, the Government teams, and U.S. Government stakeholders with a minimum of Government Purpose Rights (GPR). Unlimited government rights are preferred. Performers are strongly encouraged to establish the appropriate agreements to enable collaboration and data sharing with and beyond these organizations. DARPA encourages sharing of pre-existing data, including those generated through funding from other sources, although this is not a requirement of the program.

SECTION II: PROGRAM ANNOUNCEMENT PROCEDURE

In response to this funding opportunity proposers are asked to submit a written proposal as described in Section 3.2. This process allows DARPA to ascertain (1) whether the proposers understand the key challenges of the RAPIID program, and (2) whether they are capable of executing a proposed concept. Specific evaluation criteria used to make the assessment can be found in Section IV. After the proposal review, DARPA will make a determination as to which proposers may be selected for negotiation leading to an OT for Research agreement for Phases 1 and 2 of the RAPIID program. The Government will not pay proposers responding to this PA for the costs associated with proposal preparation and submission.

2.1 PROGRAM LENGTH

The RAPIID program has an anticipated maximum length of 36 months which is split into two, sequential phases: Phase 1 (Base, 12 months) and Phase 2 (Option, 24 months). This PA seeks proposals for both Phases with Phase 2 as a priced option. Proposals that do not include both phases may be deemed non-compliant.

2.2 QUESTION AND ANSWER (Q&A, INFORMATIONAL)

Questions can be sent to RAPIID@darpa.mil. DARPA will respond to any relevant and/or PA clarification question(s) submitted no later than 3:00 PM Eastern Time (ET) on July 10, 2026.

Consolidated Q&A documents will be posted to the DARPA RAPIID website.

2.3 WRITTEN PROPOSAL (REQUIRED)

Proposers must submit a written proposal in response to this PA to be considered for participation in the RAPIID program that addresses Phase 1 and Phase 2. Proposals shall be submitted as specified in Section 3.1 and 3.2 of this PA and reviewed by the Government using the evaluation criteria described in Section IV. Proposers must only propose an OT for Research. Please note that abstracts are not requested.

2.4 MILESTONES

Proposers must only propose fixed payable milestones. Milestones represent a completed technical event, and the milestone schedule outlines key observable events in the critical path to accomplish the program objectives. Fixed payable milestones are payments made after successful completion of the milestones agreed to in the milestone schedule. A Schedule of Milestones and Payments is mailto:RAPIID@darpa.mil https://www.darpa.mil/research/programs/rapiid included as Attachment F. Proposals may suggest modifications or additions to the Schedule of Milestones and Payments, though it is not guaranteed that these edits will be accepted by DARPA.

2.5 KEY ACTIVITIES FOR TA-3 PROPOSERS

To be considered for award, proposers should clearly demonstrate their direct experience and capability in each of the following key activities in Sections 2-4 of Attachment A. Proposals that do not provide specific, credible evidence of the prime’s ability to perform these activities will not be considered for award. Given the urgency and complexity of the RAPIID program, only organizations with established, ready-to-deploy expertise will be considered.

a. Demonstrated Sponsorship of Multi-site Trauma Clinical Trials (including EFIC): The proposer should have a documented track record as Sponsor of Record for multisite trauma clinical trials, including trials conducted under Exception from Informed Consent (EFIC) per 21 CFR 50.24.

b. In-House IND/IDE Regulatory Sponsorship Capability: The proposer should have institutional capability to hold INDs and IDEs as Sponsor of Record with the FDA.

c. CRO-like Operations: The proposer should have in-house or tightly managed CRO or Academic CRO-like operations, including multisite contracting, regulatory submissions, data coordination, statistical oversight, and site monitoring.

d. Combination/Integration Testing Capability: The proposer should be able to conduct preclinical and clinical studies involving multi-component biosynthetic blood analog components, including combination testing of products from multiple sources as well as testing of companion diagnostics/devices.

e. GLP-Compliant Large-Animal Hemorrhagic Shock Model Execution: The proposer should have access to, or direct control of, GLP-compliant large-animal models relevant to trauma and hemorrhagic shock, either in-house or under a tightly managed partnership.

Proposals should address an expedited pathway to GLP-compliance if not conducted in-house.

f. Engagement with JTS, CoTCCC, and Service Medical Leadership for CPG Development:

The proposer should have a documented record of engagement with the Joint Trauma System (JTS), Committee on Tactical Combat Casualty Care (CoTCCC), and Service medical leadership for the development of clinical practice guidelines (CPGs).

g. Peer-Reviewed Publication Record from Completed Multi-site Trauma Trials: The proposer should have a demonstrated, recent record of peer-reviewed publications from completed multi-site trauma trials, with timelines compatible with expedited decision-making.

2.6 ELIGIBILITY AND CONFLICTS OF INTEREST

2.6.1 Eligible Applicants

This PA encourages solutions from all responsible sources capable of satisfying the Government’s needs, including large and small businesses, nontraditional defense contractors, non-profit research institutions, and academia.

2.6.2 Federally Funded Research and Development Centers (FFRDCs) and Government Entities

Federally Funded Research and Development Centers (FFRDC), University Affiliated Research Centers (UARCs), and Government Entities to include National Laboratories are NOT eligible to propose to this funding opportunity, nor are they eligible as subcontractors or consultants as part of a proposal.

2.6.3 Other Applicants

Non-U.S. organizations and/or individuals may participate to the extent that such participants comply with any necessary nondisclosure agreements, security regulations, export control laws, and other governing statutes applicable under the circumstances.

2.6.4 Conflicts of Interest Between RAPIID TAs

The TA-3 mission set of regulatory sponsorship, combination testing, and clinical trial execution of products developed by other RAPIID performers are inherently sensitive to conflicts of interest.

The credibility of the integrated RAPIID system, its regulatory submissions to the FDA, and ultimately its acceptance by the Government depend on the demonstrable independence of the TA- 3 performer from the developers of the products being evaluated.

Accordingly, organizations and personnel, including all divisions, subsidiaries, affiliates, and parent entities who have previously assisted or currently assist in the development, commercialization, and/or have a financial interest in any TA-1 or TA-2 performer, product, or technology are not eligible to propose for TA-3. Scientific interaction, such as participation in research, publication, or clinical evaluation, is generally not considered a conflict, provided there is no personal financial, advisory, or commercialization interest and those individuals are not involved in TA-3 activities. For example:

Acceptable: Dr. Lee, a clinician at the TA-3 institution, previously participated in a clinical trial evaluating a blood analog product developed by a TA-1 performer. Dr. Lee’s involvement was limited to scientific data collection and patient care, with no financial, advisory, or commercialization interest in the TA-1 company or its product. Dr. Lee is not proposed for any role on the TA-3 team and has no access to RAPIID-related activities, data, or decision-making. This is acceptable, as Dr. Lee’s prior scientific interaction is unrelated to the TA-3 mission, and there are no ongoing ties or interests that would impair objectivity.

Not Acceptable: Dr. Patel, a member of the division at the proposing TA-3 institution responsible for RAPIID activities, currently serves as a paid consultant and scientific advisor for a TA-1 performer developing a blood analog product. Although the institution may claim Dr. Patel will not participate in the TA-3 effort, the group’s past performance and expertise are directly tied to Dr. Patel’s contributions. Because the proposal relies on past work or capabilities that are inseparable from a currently conflicted member, the independence and objectivity required for TA-3 cannot be assured. This is not acceptable, as the presence of a current financial or advisory relationship within the group responsible for TA-3 activities, and reliance on that individual’s past performance, creates a conflict that cannot be mitigated or separated by exclusion.

Prior collaborations or incidental professional interactions, such as co-authorship on publications or completed projects with no ongoing ties, do not constitute a conflict, provided that the organization and personnel, including all divisions, subsidiaries, affiliates, and parent entities who previously assisted or currently assist in the development, commercialization, and/or have a financial interest in any TA-1 or TA-2 performer, product, or technology are not eligible to propose for TA-3.

This prohibition also extends to any individual who is proposed and could potentially consult, advise, or influence the TA-3 work, regardless of whether they are named as key personnel. For the duration of the RAPIID program, the TA-3 performer must not have any financial, advisory, or commercial interest in any TA-1 or TA-2 performer, product, or technology. Any proposal that does not conform with the information in this section will not be evaluated and will be removed from consideration.

2.6.5 Organizational Conflicts of Interest (OCI)

Without prior approval or a waiver from the DARPA Deputy Director, a contractor cannot simultaneously provide scientific, engineering, technical assistance (SETA), advisory and assistance services (A&AS), or similar support and also be a technical performer. As part of the proposal, all members of the proposed team (including any potential subawardees or consultants) must affirm whether they (their organizations and individual team members) are currently or have recently provided SETA, A&AS, or similar support to any DARPA office(s) through prime award or subaward. All facts relevant to the existence or potential existence of OCI must be disclosed in Section 7 of Attachment A including:

The name of the DARPA office receiving the support, The prime contract number, Identification of proposed team member (subawardee, consultant) providing the support, and An OCI mitigation plan

Under this section of the PA, the proposer is responsible for providing this disclosure with its proposal submission. The disclosure must include the proposer’s OCI status, and as applicable, proposed team member’s OCI mitigation plan. The OCI mitigation plan must include a description of the actions the proposer has taken, or intends to take, to avoid, neutralize, or mitigate such conflict, prevent the existence of conflicting roles that might bias the proposer’s judgment, and prevent…