PROJECTED CMMC LEVEL REQUIREMENT
Level 1
TECHNOLOGY AREAS
Bio Medical
MODERNIZATION PRIORITIES
Military Operational Medicine
KEYWORDS
Hemorrhage control; whole blood products; whole blood substitutes; oxygen carriers; canine; military working dog
OBJECTIVE
Develop a whole blood product or substitute to aid in hemorrhage control for Military Working Dogs (MWD) after battlefield injury that can be used near the point of injury (POI) and throughout the continuum of care to reduce morbidity and mortality.
DESCRIPTION
This topic is in support of the DoD Working Dog Strategic Research Plan concerning solutions for bleeding control and coagulopathy support.
1
The Military Working Dog (MWD) provides a unique and important service to the warfighter. MWDs serve as sentries, perform tracking and patrol, and are used for the detection of explosives. These activities come with a high risk of injury. Uncontrolled hemorrhage following traumatic injury accounts for over 45% of all MWD battlefield deaths
2
. The current standard of care for hemorrhage in the MWD is to provide immediate fluid therapy through the delivery of crystalloid fluids as the first-line treatment, which is then followed by a synthetic colloid or hypertonic saline. These treatments also require the administration of supplemental oxygen to maintain appropriate oxygen levels and for the survival of the MWD
3
. To improve their survival rates, the development of a shelf stable canine whole blood product or substitute is a critical priority.
The goal of this topic is to develop a stable canine whole blood product and/or substitute (i.e. hemoglobin or polymer oxygen carriers), intended for canine use at both POI and throughout the continuum of care. The product should have a shelf-life of greater than 3 years and be thermal stable (-9 C to 60 C) to ensure accessibility in operational environments. The product must primarily replicate the oxygen carrier characteristics of whole blood and demonstrate the ability to be used safely and effectively to treat blood loss following traumatic injury. This research topic does not support the use of canines for testing purposes. Any animal testing would require use of suitable animal models that would approximate the response of a canine.
Blood products derived from canine donors must be negative for canine red blood cell antigens DEA 1.1 and DEA 1.2. Donor animals must also be tested for blood borne diseases including canine brucellosis, hemobartonellosis, Borrelia burgdorferi (Lyme disease), Dirofilaria immitis (heartworm disease), Ehrlichia canis, Rocky Mountain spotted fever, Coccidioides immitis, Babesia canis, Babesia gibsoni, Mycoplasma haemocanis and plasma levels of von Willebrand factor. All donor animals must be current on immunizations for canine distemper, hepatitis, parainfluenza, leptospirosis, parvovirus, Bordatella, coronavirus and rabies virus as applicable.
PHASE I
Identify a blood substitute solution that can meet the performance and chemical specifications for a canine
4
whole blood product or substitute. The primary specifications must include the ability to perform oxygen exchange, possess an oxygen capacity of approximately 24 ml/dL, and be compatible with the blood chemistry of a canine
4
. The proposed solution must have a shelf life of greater than 3 years and be thermally stable (-9 C to 60 C). This phase should address the feasibility of the proposed solution and end with the development of a plan for the testing of the proposed solution. The plan will include appropriate studies using in vitro and in vivo models to determine whether the solution can address the various functional aspects of whole blood that are required for being a replacement. The plan must include the descriptions and methods of determining the study endpoints to be measured for each of the specifications. The plan must address the risks and potential payoffs of the technologies that are being investigated and recommend the best option to achieve the objective. Any in vivo studies are to be planned using a suitable animal model that approximates the canine. No canine research will be performed for this topic area.
PHASE II
Develop the solution as described in Phase I to generate a shelf-stable (> 3 years) and thermal stable (-9 C to 60 C) whole blood product or substitute that possess the primary performance (ability to perform oxygen exchange, possess an oxygen capacity of approximately 24 ml/dL) and chemical characteristics
4
of canine blood. Methods for development must be amenable to large scale production and be able to produce a sustainable commercial market. Conduct the testing plan as outlined in Phase I. Testing will include an in vivo evaluation of the technology compared to crystalloid fluids (current standard of care), plasma, and whole blood in a model of severe hemorrhage/hemorrhagic shock. The size of the study must be appropriately powered to ensure that the results are statistically significant. The study must include the evaluation of the solution for the acute phase of care through 72 hours for hemorrhage/hemorrhagic shock. Any in vivo studies must be performed on an animal model that approximates the canine. No canine research will be performed for this topic area. Outcome measures of the in vivo evaluation must include survival, evaluation of tissue oxygenation, correction of coagulopathies, prevention of endothelial injury and vascular reactivity, end organ function, inflammatory markers or toxicity measures, evaluation of coagulation parameters, and evaluation of metabolic parameters. Successful prototype solutions must develop final product specification documents that list all product components and their concentrations, instructions for storage, and instructions for preparation (if required) and use of the whole blood product or substitute.
PHASE III DUAL USE APPLICATIONS
The end goal is to achieve FDA Center for Veterinary Medicine approval for this product. Transition the prototype from an advanced development stage to a fully vetted product ready for real-world use. Refine the development of a commercialization plan that may include development of different pathways, including both military and private sectors. This product should be applicable to a broad spectrum of civilian use markets, including remote and emergency veterinary facilities. In addition, the work may result in technology transition to Acquisition Program managers within DoW These efforts will be crucial in turning the prototype into a commercially viable product that can be rapidly deployed in military operations.
REFERENCES
Defense Health Agency Strategic Research Plan: Department of Defense (DoD) Working Dog, Section D4.3a. https://www.health.mil/Reference-Center/Publications/2024/06/01/DHA-Strategic-Research-Plan-DOD-Working-Dog
Causes of mortality in military working dog from traumatic injuries. Front Vet Sci. 2024 Jul 8:11:1360233. doi: 10.3389/fvets.2024.1360233. eCollection 2024.
Department of the Army, Headquarters. Veterinary Service: Tactics, techniques, and Procedures. Field manual No. 4-02.18. Pages 5-7 to 5-23. December 2004.
Clinical Practice Guidelines for Military Working Dogs. 12 December 2018, CPG ID_16
