OBJECTIVE: To reimagine the combat wound medication packet (CWMP) in a wearable format capable of delivering treatment for the prevention of infection in a prolonged care (PC) setting. The technology shall be in an easy-to-use format, durable instrumentation, lightweight, and compatible with PC. The approach should enable treatment administration for 72 hours near the wound bed. The end goal for this effort is to assemble a system of systems to prevent the development of infection in an austere environment when the provision of surgical intervention is delayed. DESCRIPTION: Multi-domain operations (MDO) of the future anticipate division-on-division combat operations with casualty volumes and medical intervention times that mirror what was observed in World War I and II. In MDO, the deployment of anti-access and area denial (A2AD) technologies will not only limit evacuation to degrade the Golden Hour timeline for medical support but also constrain medical resupply, which will leave wounded Warfighters and first line medical support providers stranded in PC scenarios for unknown duration. Furthermore, repeated events of mass casualty and greater dependency on PC (i.e. limited resources) will increase the number of deaths from wounds as the infection rate will rise in these wounds within 72 hours and beyond as was observed in previous conflicts. Here, the amount of wound dressings and antibiotics needed to prevent infection from polytraumatic wounds based on current US military medical doctrine designed for Golden Hour doctrine are untenable in PC scenarios. As a result, the need for innovative solutions that are massively scalable and distributive (i.e. affordable and for all combatants) focused on amplifying self/buddy care (i.e. fire and forget solutions that enable less supply to be carried for longer duration or the ability of one medical provider to provide care for a high number of wounded casualties) is urgent. Furthermore, adding materials to the improved first aid kit (IFAK) or combat lifesaver (CLS) bag presents significant challenges. The critical need for wound infections and sepsis mitigation at point-of-care and Role1 is to design alternative and/or adjunctive solutions that prevent infection for the first 72 hours following injury. One approach is to reimagine components of IFAK as a system of systems to prevent the development of infection in polytraumatic wounds by extending treatment over 72 hours and buying time for surgical intervention. This topic explores the current CWMP (Combat pill pack, NSN 6505-01-548-5129) as a drug delivery device to specifically meet the need for fire and forget treatment of infection for at least 72 hours in prolonged care settings without the need to carry more pill packs and track of treatment administration. In MDO (TRADOC PAM 525-3-1), especially those involving large scale combat operations, the deployment of Golden Hour medical doctrine from OEF and OIF is not tenable and new weapon systems by near-peer adversaries to deprive superiority on land, sea, and air anticipates accumulation of large volumes of casualties with complex wounds of wide variety without medical evacuation for surgical intervention for unknown duration. In this scenario, the ability to treat penetrating combat wounds for longer duration becomes paramount to limit mortality and morbidity. Operationally, the ability to treat even minor breaks in the skin and prevent infection underpins the instruments of maintaining combat power. Here, numerous studies have demonstrated that the timing of antibiotic treatment significantly correlated with the infection development process. Animal studies of open fractures revealed that early antibiotic treatment and surgical debridement within 2 hours prevented infection, but delayed administration of antibiotics and surgery after 2 hours significantly increased the development of infections. These observations were further validated in retrospective clinical studies in civilian trauma involving open fractures and further studies have revealed that administering antibiotics immediately after traumatic injury reduced infection rates significantly (i.e. 7% of infection if treated within one hour to 28% if treated after 1.5 hours). According to the Tactical Combat Casualty Care (TCCC) guidelines (available online), the initial response to injury recommends administration of moxifloxacin (400 mg, PO once a day) from the CWMP. The current CWMP also contains two slow-release bilayer Tylenol caplets (650 mg, PO every 8 hours) and meloxicam (15 mg, PO once a day). Unfortunately, adherence to CWMP intervention for injury patterns meeting indications set by TCCC guidelines is very low for a variety of reasons including hierarchy of life-saving interventions and lack of oral administration tolerance by casualties. The conceivable lack of a reasonable timeframe for medical evacuation in large scale combat operations and issues of compliance with CWMP intervention for the prevention of infections requires the adaption of PC to the new operational environment to meet the balanced need for ease-of-use, scalability, longevity treatment, and efficiency of treatment delivery focused on point-of-injury and Role 1 care. The ultimate goal of the technology in this request is, but not limited to, to automate treatment delivery in a wearable format as a convergent technology to increase treatment delivery at the earliest time possible after injury for an extended duration without additional attention from a medical provider with respect to treatment administration for relevant injuries. In doing so, this convergent technology should prevent infection development, enable dose adjustment based on weight of warfighter, customize treatment, overcome compliance with the combat wound medication packet (CWMP) usage, and extend treatment duration all in one single step at point-of-injury and Role 1. The aim of this SBIR/STTR is to develop and commercialize a technology that addresses the unmet need of delayed definitive care and to accelerate the next generation of medical innovations that increase, but not limited to, the efficiency treatment delivery at point-of-injury and Role 1 care. Offerors are encouraged to familiarize themselves with the TCCC handbook, TCCC pharmacology, and field medicine literature. When proposing a wearable technology, it is paramount, but not limited to, to consider the factors below: 1) The starting technology must plan to have or already has Food and Drug Administration (FDA) or equivalent clearance as a wearable device 2) The packing dimensions should not exceed CWMP generations (i.e. LxWxH- 2x2x0.5 in) 3) The system design should accommodate suitable formulations for the TCCC pharmacology and the route of administration for multiple days of application 4) Modular designs with a library of medications incorporating exchangeable cartridges, microneedles, micropumps, catheters, gels... etc. are welcomed, but should describe a ruggedization plan and durability of design 5) Designs must have a manual fail-safe backup option for motorized or automated designs. Use of adhesives must consider human skin safe products. 6) Treatment for prevention of infection shall start with TCCC pharmacology, but not limited to, other small molecule-based antibiotics, metal ions, lantibiotics, natural products, bacteriophages, antibodies, polymers, nano-fibers/sponges, antimicrobial peptides, and or any pathogen agnostic treatment. Stable formulations with long shelf-life should be considered. 7) Other treatments such as analgesics for pain management are optional but preferred 8) Dose customization features are optional 9) Built in sensors are optional 10) Ease of application, ability to withstand water, high positive and negative pressures, hot and cold temperatures and minimal storage conditions will be factored in the nomination process PHASE I: Given the short duration of Phase I and the high order of technology integration required for Phase II, Phase I should focus on system design and development of proof-of-concept prototypes that address the treatment delivery requirement. Starting material may include off the shelf commercially available wearable technologies with proper agreements. Proposals may include different formulations of treatments. Prototypes may combine classes of applications into different sets of designs. At the end of this phase, fabricated prototypes should demonstrate feasibility, ease-of-use, proof-of-concept and establish release profile , using relevant test beds for the proposed technology. This phase should down-select designs as well as identify a pre-clinical animal model, such as, but not limited to, open fracture or soft tissue wounds with and without infection for use in Phase II. PHASE II: During this phase, the lead integrated system should be further refined from proof-of-concept into a viable product. Further optimization of technology for deep penetration of treatments and prevention of infection should be demonstrated during this phase. Evaluation of the product's efficacy both antimicrobial activity must include data for the first 6, 24, 48, and 72 hours at a minimum, if not longer. Qualitative and quantitative outcomes of product with regards to prevention of infection, and/or decolonization by invading organisms must be demonstrated as specific performance characteristics of the product. This testing should be controlled, and rigorous.. Testing and evaluation of the prototype to demonstrate operational effectiveness in simulated environments shall be demonstrated. Here, the selected offeror/contractor may choose but not required to coordinate or consult with WRAIR/NMRC for control of infection as testing site and models if needed. Contract research organizations (CROs) and Universities are suitable partners at the phase. Stability of product in an austere environment should be evaluated to include extreme conditions (i.e. extreme heat, cold, wet environment). This phase should also demonstrate evidence of commercial viability of the product. Accompanying application instructions, simplified procedures and training materials should be drafted in a multimedia format for use and integration of the product into market. The offeror may define and document the regulatory strategy and provide a clear plan on how FDA clearance will be obtained at the end of this phase. Offeror should also consider a pre-pre-submission communication with the FDA. PHASE III DUAL USE APPLICATIONS: This phase should encompass both large animal models and randomized clinical trials that would require formal IRB approval as well as shelf-life optimization of at least 120 days to 2 years in austere environments. The ultimate goal of this phase is work closely with USAMMDA and the Warfighter Expeditionary Medicine and Treatment (WEMT) office to secure funds to develop and demonstrate a technology enabling the prevention of infection in wounded service members from infected traumatic combat wounds under PC with proper regulatory (FDA) clearance or authorization for human or Department of Defense use exemption. If funded, this effort will focus on coordinated activities to seamlessly integrate product into the TCCC paradigm of initial response to trauma. Once developed and demonstrated, the technology can be used both commercially in civilian or military settings to increase efficiency of treatment delivery. For instance, wound infections are projected to account for 27 billion dollars of the market size by 2026 and the post-surgical treatment care over 10 billion dollars. Performer should formulate a plan to penetrate this market. The selected contractor shall make this product available to potential military applications beyond prevention of infection to include analgesic, medical countermeasures for Chemical, Biological, Radiological, and Nuclear (CBRN) Injury, human performance augmentation solutions, and anti-sepsis treatment. Price estimate and comparison analysis for new design relative current fielded equipment shall be provided. The contractor should coordinate with Medical Research and Development Command (MRDC) to establish a National Stock Number (NSN) as the first step towards the potential inclusion into appropriate "Sets, Kits and Outfits" that are used by deployed medical forces in the Defense Acquisition System. If the product is transitioned into Acquisition Programs of Record, the Government may work with performer to harmonize design with other relevant products. REFERENCES: 1. Saeed O, et al. Infection prevention in combat-related injuries. Mil Med 2018;183: 137 141 2. Benov A, et al. Antibiotic treatment-what can be learned from point of injury experience. Mil Med 2018;183: 466 471 3. Schauer SG, et al. Prehospital combat wound medication pack administration in Iraq and Afghanistan: a Department of Defense Trauma Registry Analysis. J Spec Oper Med 2020; 20(3): 76-80 4. Butler FK, et al. Tactical combat casualty care and wilderness medicine: Advancing trauma care in austere environments. Emerg. Med. Clin North Am 2017; 35(2): 391-407 KEYWORDS: MDO, drug delivery, wearable, trauma, prolonged care
