DoD SBIR 23.3 BAA

Active
No
Status
Closed
Release Date
August 23rd, 2023
Open Date
September 20th, 2023
Due Date(s)
October 18th, 2023
Close Date
October 18th, 2023
Topic No.
DHA233-001

Topic

Rapid Diagnostic for Invasive Fungal Infection

Agency

Department of DefenseN/A

Program

Type: SBIRPhase: BOTHYear: 2023

Summary

The Department of Defense (DoD) is seeking proposals for the development of a rapid diagnostic for invasive fungal infection (IFI) in military treatment facilities or lower levels of care within 24 hours. IFIs are associated with significant morbidity and mortality, and early identification and treatment are crucial. Current diagnostic methods are often delayed and insensitive, requiring clinical and microbiological expertise. The DoD is looking for a technology that can quickly and accurately diagnose the presence of a wound-IFI, determine the causative agent, and potentially determine antifungal drug susceptibility. The technology should be easy to use, require minimal training, and be compatible with wet/dry environments and long-term storage. The project will have a Phase I focused on system design and development of proof-of-concept prototypes, followed by a Phase II for further refinement and optimization. The ultimate goal is to secure FDA approval and commercialize the technology, with potential applications in both civilian and military settings. The project duration and funding specifics are not provided in the document. For more information, visit the SBIR topic link or the solicitation agency website.

Description

OUSD (R&E) CRITICAL TECHNOLOGY AREA(S): Military Infectious Disease

OBJECTIVE: Develop a technical solution or device for the identification of an Invasive Fungal Wound Infections in a Military Treatment Facility or lower Role of Care within 24 hours.

DESCRIPTION: Trauma-related invasive fungal wound infections (IFIs) are associated with significant morbidity and mortality (8-12% mortality). Early identification and treatment are critical to prevent loss of limb and/or loss of life. Traditional identification methods can be delayed and insensitive and are heavily dependent on clinical and microbiological expertise. At presentation for clinical treatment, differential diagnoses for deep necrotizing wounds leans heavily towards infections caused by multi-drug resistant (MDR) bacteria. During initial wound assessment, clinicians must have a heightened sense of IFI suspicion, often requiring a high degree of expertise, in order to clinically differentiate between bacteria or fungal infections. Current clinical laboratory diagnostics involve direct examination of cultures and histopathology of collected wound tissue specimens. Fungal cultivation, the current standard diagnostic method, has numerous disadvantages including, but not limited to a low sensitivity (only 50% of the patients present positive fungal cultures) and long growth time. These factors delay patient treatment and consequently lead to longer hospital admissions and higher hospital costs. Clinical laboratory diagnosis can take, at best, between 24-72 hours or at worst, 6-8 weeks, to positively confirm and identify an IFI. The benefit of fungal isolation from tissue culture includes direct evaluation of clinically relevant characteristics such as antifungal resistance and species identification. However, fungal speciation through culture requires considerable expertise for identification.

Currently, there are no commercially available products that can quickly and accurately clinically diagnose the presence of a wound-IFI as well as quickly speciate and determine antifungal drug susceptibility. Many IFI’s go undiagnosed due to the high level of clinical and microbiological experiences required. The envisioned system would employ a technology using an innovative engineering approach that enables infection identification. In addition to the primary objective of determining the causative agent of an ongoing IFI, such a device would also enable prospective monitoring of patients at risk for IFI, such as severely immunocompromised individuals, enabling early treatment before the occurrence of overt symptoms. If adapted to a DOD product the proposed technology is envisioned to be utilized at the Role 3 or potentially Role 2+ alongside analogous bacteriological diagnostics in a prolonged field care type environment occurring during Large Scale Combat Operations.

The technology is not limited to but may consider, the factors below:

  1. The technology must include a plan for FDA clearance
  2. Detection and identification of IFI via built-in antigen tests, nucleic acid assays, VOC sniffers, chemical/molecular detector, photonics …etc. must be contiguous in one platform with minimal user training
  3. Technology should have the ability to distinguish between common clinical fungal agents of infection with no downstream analysis required. Examples include, but are not limited to: Order Mucorales, Aspergillus sp, Fusarium sp., +/- Scedosporium sp., and agents of phaeohyphomycosis
  4. Technology should be capable of operating continuously or successively in a high throughput as well as an on-demand between samples with minimal number of steps
  5. The ability to determine antifungal drug susceptibility is preferred but optional
  6. Engineering solutions overall should require minimum logistical support, should be compatible with applications in wet/dry environments, and stable in long term storage including hot (~100℃) and cold temperature (-20℃)
  7. Ease of use, technology should be operable with little training or background with unambiguous primary output

Technologies with the following features are not the primary focus of this topic

  1. Microscopy based automated or manual morphology description methods
  2. Methods involving staining and/or adhesive tape
  3. Established methods involving mass spectrometry workflow
  4. Technologies involving radioactive agents

PHASE I: Given the short duration of Phase I and the high order of technology integration required, Phase I should focus on system design and development of proof-of-concept prototypes that address the diagnostic capability requirement. Proposals may include early versions diagnostic systems that may combine “classes” of applications into different “sets” of designs. At the end of this phase, fabricated prototypes should demonstrate detection along a continuum of growth as feasibility, proof-of-concept and establish reasonable qualitative identification, using relevant testing platforms for the proposed technology. This phase should down-select promising design with sufficient performance specification superior to current standards in the laboratory. Evaluation of the product’s durability for detecting IFI and must include data for 6, 12, 18, and 24 hours of in vitro testing at a minimum. The above time points do not represent system application on subjects but used as a benchmark and quantify efficacy of detection of infection.

PHASE II: During this phase, the lead integrated system should be further refined from proof-of-concept and begin planning compatibility with CLIA standards for the clinical laboratory. Further optimization of the technology for earlier and more robust detection of infection at a traumatized wound bed should be demonstrated during this phase. Qualitative and quantitative outcomes of product with regards to quantification of spores/hyphae, identification of invading organism, and/or characteristics of such as anti-fungal susceptibility if feasible. This testing should be controlled and in rigorous conditions. Accompanying application instructions and simplified procedures should be drafted in a multimedia format for use and integration of the product into market. At this stage, offers may begin developing plans and documents for quality control material, training materials, proficiency assessment tools and materials, device verification and validation documents, supporting material for Individualized Quality Control Plan for easy adoption of technology as a nonwaived test. Price estimate and comparison analysis for new designs relative to current fielded equipment shall be provided to forecast the potential cost of the product and commercial viability. The offeror shall articulate the regulatory strategy and provide a clear plan on how FDA clearance will be obtained.

PHASE III DUAL USE APPLICATIONS: The ultimate goal of this phase is to secure an FDA approved device to commercialize a technology enabling the early detection of fungi. Additional use cases may be included in order to derive, extend, or complete the funded innovation. The growing use of immunosuppressive drugs to treat various diseases such as HIV will likely increase the incidence of IFIs in civilian populations. The global market for fungal therapeutics is expected to grow from $7.2 Billion in 2021 to $10 billion by 2030. The clinical diagnostic space will be critical in leveraging this growing market segment. Alternatively, further development, testing and evaluation of the product developed in phase II of this SBIR can be supported by BARDA, CDMRP, JWMRP, and other DOD opportunities. Once developed and demonstrated, the technology can be used commercially in both civilian and military settings to save lives. If the product is transitioned into Acquisition Programs of Record, the Government retains the right to harmonize design with other relevant products.

REFERENCES:

  1. Tribble DR, Ganesan A, Rodriguez CJ. Combat trauma-related invasive fungal wound infections. Curr Fungal Infect Rep. 2020 Jun;14(2):186-196. doi: 10.1007/s12281-020-00385-4. Epub 2020 Apr 16. PMID: 32665807; PMCID: PMC7360332.
  2. Ganesan, Anuradha, et al. "Molecular detection of filamentous fungi in formalin-fixed paraffin-embedded specimens in invasive fungal wound infections is feasible with high specificity." Journal of clinical microbiology 58.1 (2019): e01259-19. https://doi.org/10.1128/JCM.01259-19
  3. Mendonca, Alexandre, et al. "Fungal infections diagnosis–Past, present and future." Research in Microbiology 173.3 (2022): 103915. https://doi.org/10.1016/j.resmic.2021.103915
  4. Kozel, Thomas R., and Brian Wickes. "Fungal diagnostics." Cold Spring Harbor perspectives in medicine 4.4 (2014): a019299. doi:10.1101/cshperspect.a019299
  5. Terrero-Salcedo, David, and Margaret V. Powers-Fletcher. "Updates in laboratory diagnostics for invasive fungal infections." Journal of Clinical Microbiology 58.6 (2020): e01487-19. https://doi.org/10.1128/JCM.01487-19

KEYWORDS: Infection, Diagnosis, Trauma, Fungal Pathogen, Clinical Device