Pre-Announcement “Advancing Biodefense Readiness: On-Demand Biologics, Automated Threat Detection, and Alternative MCM Testing in High Containment”

Purpose

The Medical Technology Enterprise Consortium (MTEC), in support of the Defense Threat Reduction Agency (DTRA), is excited to post this pre-announcement for an upcoming Request for Project Proposals (RPP) focused on advancing three medical and bioengineering technologies. The intent of the upcoming RPP is for interested Offerors to respond to only one of the following Focus Areas; however, it is permissible for an Offeror to submit a separate white paper in response to one or more of the focus areas:

FOCUS AREA #1: Biologics On Demand: This focus area (which is further detailed below) aims to advance the state-of-the-art for producing biologics on-demand and near point-of-need with the following characteristics:

• Achieving relevant quantities of medical countermeasures (MCM).
• Ensuring initiation of protein production within ~24 hours of receiving DNA/RNA template.
• Producing fully bioactive complex proteins.
• Demonstration of identical runs at different locations.
• Feasibility to advance products to and through regulatory approval.
  

FOCUS AREA #2: Automated Clinical and/or Environmental Sampling, Sequencing, and Analysis: This focus area (which is further detailed below) aims to advance the development of an integrated, automated system capable of detecting and identifying biological threats in environmental samples with the following characteristics:

• Automated collection of representative samples from various sources (air, water, wastewater, NP swabs, serum, plasma, urine, etc.).
• Onboard liquid handling for nucleic acid extraction and library preparation.
• Integration with a platform that can provide real-time sequencing and identification of biological agents in environmental matrices.
• Embedded bioinformatics tools for immediate analysis and reporting of sequencing data.

FOCUS AREA #3: Alternative Methods for Testing MCMs in High Containment: This focus area (which is further detailed below) aims to advance alternative models, such as organ-on-a-chip (OoC) and organoid systems, for evaluating MCMs against viral biothreats. Solutions will validate mature alternative model platforms that model human infection and therapeutic response, with a focus on aerosol exposure and oral delivery methods. Solutions are expected to compare alternative model data to animal and clinical results, enabling regulatory confidence and operational use in high-containment environments.

Background:

The DTRA Chemical and Biological Technologies Department (RD-CB), in its role as the Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense Program (CBDP), manages a broad portfolio of basic and applied research and advanced technology development activities to support critical chemical and biological (CB) defense missions.

This upcoming RPP seeks solutions to the following three focus areas. Note that the following focus areas and associated details described below are subject to change as the RPP is developed.

**To view the full-length version of this Pre-Announcement, please download using the link on this page.

Scope of Work

FOCUS AREA #1 - BIOLOGICS ON DEMAND

Background: The Department of Defense (DoD) currently faces slow response times for critical protein-based MCMs due to the limitations of traditional protein production methods, which require extensive, centralized infrastructure and complex processes. This results in several-month production times and further delays in deploying MCMs.

High priority MCMs include Granulocyte-Colony Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony-Simulating Factor (GM-CSF), host therapy biologics that stimulates the production of neutrophils, a type of white blood cell essential for fighting infection. Another high priority MCM is Griffithsin (GRFT), a direct acting broad-spectrum antiviral. Monoclonal antibodies are also of interest.

Distributed manufacturing approaches could significantly shorten the timelines for production, making MCM deployment more relevant to DoD needs, especially in challenging operational environments. Continued advances in biologics-on-demand technology make regulatory evaluation possible.

Current challenges of distributed biomanufacturing systems are that they produce lower volumes compared to conventional facilities and regulatory evaluation. While there exist numerous possible applications for such a biologic-on-demand capability, this solicitation is primarily focused on developing a system for FDA review.

Objective: This upcoming solicitation aims to support the development and demonstration of a deployable, on-demand protein manufacturing system capable of consistent production and analytical validation across distributed locations. The system must be compact, automated, and able to produce high-quality biologics suitable for regulatory review.

Solution Requirements: The US Government is seeking a solution capable of satisfying the following capabilities:

1. Prototype capable of manufacturing G-CSF, GM-CSF, or Griffithsin. Offerors are encouraged to include data within their proposal to help demonstrate this capability. While the Government is open to alternative suggested medical countermeasures, preference will be given to proposed efforts focused on G-CSF, GM-CSF, and/or Griffithsin.
2. Automated control and real-time monitoring system. This may include AI module development and machine learning for training runs.
3. Product testing and validation. This may include standard analytic techniques to ensure purity, quantity, amino acid sequence conformity, and other characteristics. In addition, produce will be provided to the DOD or designated facility for evaluation.

FOCUS AREA #2 - Automated Clinical and/or Environmental Sampling, Sequencing, and Analysis

Background: Medical chemical and biological research at USAMRDC supports the mission of the CBDP to provide chemical and biological defense capabilities in support of national military strategies. CBPD is seeking solutions for an automated sample extraction and library preparation device for military end users for hands-free preparation of a bacterial, viral, or fungal sample for metagenomic sequencing. The prototype device will enable automatic preparation for environmental and clinical sample. The prototype device is expected to extract the nucleic acid, convert, if necessary, RNA to cDNA, build libraries for sequencing and initiate the sequencing reactions. In addition, a modular device that analyzes the data as it is created, and alert users if pathogens are present would be highly desirable. A related task will be to build a device that fills disposable cartridges that must be pre-filled with the correct volume of reagents prior to use. This innovative system will reduce cold-chain logistics challenges and operational complexity and significantly enhances mission readiness by automating reagent preparation directly at the deployment site. The solution will empower any operator, regardless of specialized laboratory training, to rapidly prepare sequencing consumables, providing operators with unparalleled flexibility and operational agility.

Objective: The objective of any resulting prototype project is to develop an integrated, automated system capable of detecting and identifying biological threats in environmental and/or clinical samples.

Solution Requirements: The US Government is seeking a prototype that meets the following criteria:

1. Liquid Handling Integration: Proposed solutions shall incorporate automated liquid handling systems compatible with existing library preparation protocols, such as ligation sequencing and barcoding. The liquid handling capability must ensure precise reagent dispensing and sample manipulation to maintain consistency, sample integrity without cross contamination, and reduce human error.
2. Sequencing Platform Compatibility: The Offeror shall design a system that can interface seamlessly with capabilities able to sequence and provide real-time data acquisition. Adaptive sampling capabilities may be beneficial.
3. Bioinformatics and Data Management: The Offeror may integrate onboard computational resources capable of running sequencing pipelines for base calling, alignment, and taxonomic classification. This also may include offline data analysis, secure data storage solutions with options for cloud-based data sharing and analysis.
4. System Automation and User Interface: The Offeror shall develop a user-friendly interface for system control, monitoring, and data visualization. In addition, the Offeror shall implement automated workflows from sample collection to data reporting, minimizing the need for manual expertise and intervention.

At the end of the period of performance, the Offeror is expected to:

• Deliver a fully integrated prototype for automated sampling, processing, sequencing, and data analysis (optional).
• Validate system performance in detecting pathogens or agents of interest in environmental and/or clinical samples.
• Demonstrate scalability of the system for deployment in military settings.

FOCUS AREA #3 (Alternative Methods for Testing MCMs in High Containment)

Background: The DoD relies heavily on traditional animal models to assess the safety and efficacy of MCMs being developed to protect warfighters from chemical and biological threats. However, this reliance poses significant challenges, including unpredictable animal availability, high costs, ethical concerns, and translational limitations.

Alternative methods (AMs), such as microphysiological systems (MPS), OoC technologies and organoids, offer a promising solution to these challenges. These technologies have the potential to more accurately model human biology, reduce reliance on animal testing, and accelerate the development and evaluation of MCMs.

To realize their full potential for DoD applications, AMs must demonstrate that they can replicate infection/exposure dynamics and MCM effects observed in traditional animal models and human clinical data. This is critical for regulatory acceptance and operational integration.

One of the primary challenges is that very few have been incorporated into high containment laboratories. While there are many AM technologies in development, this solicitation is primarily focused on technologies that are fully developed, capable of incorporating multi-organ systems into a single technology, and ready for exposure studies and MCM testing in a high containment environment (i.e., biosafety level (BSL)-3 or BSL-4 environments).

Objective: Proposed solutions will leverage single and multi-organoid OoC systems to investigate viral threats, initially using surrogates and progressing to actual threat agents. Solutions will also explore novel infection delivery methods, including aerosol exposure, and evaluate the efficacy of therapeutic interventions administered via various routes, including an "oral" organoid model. This work will support the development of countermeasures against biothreat agents and contribute to a more comprehensive understanding of disease pathogenesis. This effort will also explore the considerations for using OoCs in a high containment environment.

Solution Requirements: The US Government is seeking a solution capable of satisfying the following capabilities:

• Validate single and multi-organoid OoC systems suitable for modeling biothreat agent infections (Offeror is able to propose any high containment pathogens that could be of interest to the DOD).
• Characterize the infection dynamics of viral biothreat agents and their surrogates in OoC systems.
• Evaluate the efficacy of existing and novel therapeutic interventions against biothreat agent infections in OoC systems.
• Compare OoC data with existing clinical and animal model data to assess the predictive validity of the platform.
• Test new therapies that are in development at the Joint Science and Technology Office (JSTO).
• Evaluate different infection delivery methods, with a focus on aerosol exposure for viral infections.
• Evaluate the administration of therapies via an "oral" organoid model in both infected and uninfected organoids.
• Address the operational, biosafety, and technical considerations associated with use of OoC technology in high containment labs.

Potential Funding Availability and Period of Performance:

Due to the wide variety and inherent diversity of focus areas being solicited for in this upcoming RPP, the funding amount, expected periods of performance (PoP), number of anticipated awards, and timing of funding availability for each focus area is outlined briefly below but are subject to change. The USG may apply additional dollars for follow-on efforts via post award modification to any resultant award(s) after the evaluation and acceptance of work and cost plan. Dependent on the results and deliverables, additional time may be added to the period of performance for non-competitive follow-on tasks.

Focus Area 1 – Biologics on demand: The government anticipates making a single award of ~$2-3M per year with an initial PoP not to exceed 36 months. Offerors are encouraged to propose up to $6M of follow-on tasks for additional option years.

Focus Area 2 – Automated environmental sampling, sequencing, and analysis: The government anticipates having ~$2.4M total for a single award with a PoP not to exceed 12 months.

Focus Area 3 – Alternative Methods for Testing MCMs in High Containment: The government anticipates having up to $5M for a single award with an initial PoP not to exceed 12 months. Offerors are encouraged to propose up to $19.45M of follow-on tasks for additional option years.

Acquisition Approach:

This upcoming RPP will be conducted using a two-staged approach. In Stage 1, Offerors are invited to submit White Papers using the mandatory format provided in the upcoming RPP. Based on the Government’s evaluation of White Papers in Stage 1, select Offerors will be invited to participate in Stage 2 and will be required to submit a full proposal for more detailed evaluation. The Government will evaluate all Proposals submitted and select those that best meet their current priorities using the evaluation criteria described in the upcoming RPP.

The upcoming RPP will be posted to the MTEC website (https://mtec-sc.org/solicitations/) and a summary version will be available on SAM.gov to notify interested parties. The RPP is expected to be released as soon as possible and will have a proposal preparation period of approximately 30 days. MTEC membership is required for the submission of a proposal in response to the upcoming MTEC RPP. To join MTEC, please visit https://mtec-sc.org/join.

MTEC:

The MTEC mission is to assist the U.S. Army Medical Research and Development Command (USAMRDC) by providing cutting-edge technologies and supporting life cycle management to transition medical solutions to industry that protect, treat, and optimize Warfighters’ health and performance across the full spectrum of military operations. MTEC is a biomedical technology consortium collaborating with multiple government agencies under a 10-year renewable Other Transaction Agreement (OTA), Agreement No. W81XWH-15-9-0001, with the U.S. Army Medical Research Acquisition Activity (USAMRAA). MTEC is currently recruiting a broad and diverse membership that includes representatives from large businesses, small businesses, “nontraditional” defense contractors, academic research institutions and not-for-profit organizations.

Points of Contact

For inquiries regarding this pre-announcement, please direct your correspondence to Dr. Lauren Palestrini, MTEC Chief Science Officer, lauren.palestrini@mtec-sc.org