TECHNOLOGY AREA(S): Biomedical
OBJECTIVE: Develop a stable, lyophilized plasma formulation for rapid use in canine trauma resuscitation that demonstrates safety and efficacy.
DESCRIPTION: Military Working Dogs have proven to be a vital component of significant warfighter missions, supporting warfighter security and mission implementation. A lack of appropriate canine transfusion products risks the lives of these dogs, as well as the success of the mission, when a dog suffers severe trauma in the field. Plasma is increasingly recognized as a life-saving product for severe trauma offering advantages over transfusion of blood alone. However, the use of plasma in battlefield situations is limited by logistical constraints. Maintaining stability of the plasma components often requires refrigeration or freezing, and the sheer bulk of the product hinders transport and distribution. However, lyophilized plasma provides a transfusion product with reduced volume, elimination of the need for cold storage, and the potential to concentrate anti-inflammatory molecules which may provide an added advantage. To date, experimental studies have demonstrated benefits of lyophilized plasma in a swine model, but with no other animal species.
The goal of this topic is to develop a stable, lyophilized plasma formulation that, when reconstituted, demonstrates safety and efficacy in canine trauma resuscitation. Plasma should be derived from healthy donor dogs that are negative for canine red blood cell antigens DEA 1.1 and DEA 1.2. Donor animals should 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 should be current on immunizations for canine distemper, hepatitis, parainfluenza, leptospirosis, parvovirus, Bordatella, coronavirus and rabies virus.
PHASE I: Develop methodology to collect and lyophilize canine plasma from healthy donor dogs meeting the blood type requirements cited above. Develop a reconstitution protocol that does not alter coagulation factor activity, pH or albumin levels compared to fresh plasma. The reconstitution protocol must be conducted with sterile water in less than 2 minutes. Demonstrate that following reconstitution, the product is negative for endotoxin and other hazardous components. Present a complete description of the lyophilized plasma product that clearly describes all components and/or additives and their relative abundance. Demonstrate safety and efficacy of the reconstituted lyophilized plasma product in vitro, as well as in experimental animal infusions. Evaluations should include, but are not limited to: coagulation factor levels, hematology, inflammatory profiles, and vital signs.
The objective of this USSOCOM Phase I SBIR effort is to conduct and document the results of a thorough feasibility study to investigate what is in the art of the possible within the given trade space that will satisfy a needed technology. The feasibility study should investigate all known options that meet or exceed the minimum performance parameters specified in this write up. It should also address the risks and potential payoffs of the innovative technology options that are investigated and recommend the option that best achieves the objective of this technology pursuit. The funds obligated on the resulting Phase I SBIR contracts are to be used for the sole purpose of conducting a thorough feasibility study using scientific experiments and laboratory studies as necessary. Operational prototypes will not be developed with USSOCOM SBIR funds during Phase I feasibility studies. Operational prototypes developed with other than SBIR funds that are provided at the end of Phase I feasibility studies will not be considered in deciding what firm(s) will be selected for Phase II.
PHASE II: Optimize the methodology to generate lyophilized canine plasma and the reconstitution protocol. Methods should be amenable to large scale production and economically sound. Evaluate the safety and efficacy of the lyophilized canine plasma product in a controlled canine clinical trial. All transfusion complications and adverse reactions should be noted. Evaluate the stability of the lyophilized plasma product and establish an expiration date. A shelf-life of greater than 2 years stored at 15°F-140°F is required. Develop final product specification documents that include a list of all product components and their concentrations, instructions for storage of the lyophilized plasma, instructions for reconstitution, instructions for administration, and a list of all chemicals and medications that may cross-react with the reconstituted plasma product.
PHASE III DUAL USE APPLICATIONS: The development of a lyophilized canine plasma product that meets the requirements outlined above will support the effective treatment of canine trauma in military and law enforcement settings, as well as civilian veterinary care capabilities, particularly in remote and rural areas. Canine and human physiology are similar, therefore products that can demonstrate proof-of-principle in the dog will have significant predictive value for new and innovative treatments for human trauma victims. The proposer should identify appropriate collaborative or transition partners who will be able to make this technology commercially available for the Military Working Dog.
REFERENCES:
Steil L, Thiele T, Hammer E, Bux J, Kalus M, Völker U, Greinacher A. Proteomic characterization of freeze-dried human plasma: Providing treatment of bleeding disorders without the need for a cold chain. Transfusion (2008); 48(11):2356-2363.
Spoerke N, Zink K, Cho SD, Differding J, Muller P, Karahan A, Sondeen J, Holcomb JB, Schreiber M. Lyophilized plasma for resuscitation in a swine model of severe injury. Archives of Surgery (2009); 144(9):829-834.
Van PY, Hamilton GJ, Kremenevskiy IV, Sambasivan C, Spoerke NJ, Differding JA, Watters JM, Schreiber MA. Lyophilized plasma reconstituted with ascorbic acid suppresses inflammation and oxidative DNA damage. Journal of Trauma (2011); 71(1):20-25.
KEYWORDS: Plasma, Canine, Lyophilized, Reconstituted, Trauma, Transfusion
Show All
