Description:
OBJECTIVE: Develop and demonstrate a drug delivery platform that is compact, lightweight, and robust for field use. This drug injection platform should enable the rapid injection of reconstituted wet-dry formulations in addition to single component wet and multi-component wet formulations, typical of next-generation chemical, biological, and toxin (CBT) antidotes. DESCRIPTION: The modern Warfighter is experiencing a progressively more complex battlespace. Threats from weapons of mass destruction such as chemical, biological, and toxin (CBT) weapons are increasing, and are more likely to occur with minimal warning to the Warfighter. These threats require the Warfighter to have ready access to state-of-the-art CBT antidotes in delivery systems that are: Field-ready, robust & reliable Easy & rapid to use Environmentally stable Compact & lightweight Next generation antidote compounds are often expensive, chemically complex and lack stability [thermal, oxygen, UV, shear] in solution. Dry antidote formulations represent one successful approach to address those issues of stability. This leads to a need for an injection technology that can store, reconstitute, and inject the antidote formulation rapidly in the field. Current autoinjectors have met previous needs but have a limited ability to handle next-generation antidotes. Existing nerve agent autoinjectors, for instance, have some of the following limitations: Compound specific (not platform based) May contain glass or other fragile materials, less than ideal for field deployment Large and awkward to carry by or for the Warfighter Not optimized for thermal and chemical stability Not optimized for next generation antidotes including large molecules, biologically-derived compounds, and other labile materials Existing autoinjectors incorporate pre-filled syringe technology. While there have been some developments to include polymer or plastic-based materials, current technology often exposes the pharmaceutical product to metals and other materials of construction that accelerate the degradation and/or contamination of the stored pharmaceutical ingredient. Based upon these challenges to fielding future CBT antidotes, the Department of Defense (DoD) sees a need for an autoinjector technology that provides the Warfighter with a compact, field-ready, cost-effective platform for the long-term storage of any given CBT antidote that does not present a significant logistical burden. This drug injection platform ideally can handle single component wet, multi-component wet, and wet-dry formulations. This drug injection platform would be sized for optimum portability. CBT antidotes, as post-exposure therapies, are envisioned to be either medic carried or in personally carried, self- or buddy administered drug-delivery devices for intramuscular or subcutaneous injection. Administration may or may not be required through personal protective equipment. However, intravenous injection is not suitable for field use. An example of an innovative technology that may be considered for a future CBT antidote-delivery platform are microelectromechanical (MEMS) systems. MEMS have been used to create complex mechanical and fluidics structures in a small volume using established, low-cost manufacturing techniques.1 These systems have been used to rapidly and accurately detect the presence of target compounds in the environment and in the human body.2,3 These systems are only now being applied to drug delivery systems.4 The goal of this topic is to develop a drug delivery platform capable of being approved by the FDA that will be robust & reliable, easy-to-use for the Warfighter, compact, and lightweight. Ideally, this drug delivery system will be small enough to hang on the Warfighter's ID tags or by its compact size, be readily portable by combat medics. PHASE I: Key functional technology is proved computationally and, at a minimum, at the bench scale. This could include both mechanical and fluid simulation and/or testing that would support the effectiveness and compact dimensions of the final autoinjector. Prototyping and testing of systems and subsystems that enable the path to a compact, drug injection platform would be successfully completed using suitable pharmaceutical compounds or simulants of fielded or future CBT antidotes. PHASE II: The overall device design will be finalized and the prototypes of the drug delivery system manufactured and demonstrated. All of the systems and subsystems in the device will be optimized and documented. The small business firm will show the functionality of the device for the injection of typical liquid, multi-liquid, and/or wet/dry component pharmaceutical systems that are commensurate with fielded or future CBT antidote regimens (i.e., administration by the next-generation delivery technology is suitable to deliver efficacious pharmaceutical levels of a CBT therapy). This testing will show the consistent functionality and field suitability of the resulting autoinjector platform. The small business will demonstrate to the DoD how their device is consistent with FDA guidelines and could be approved for drug injection via the 510(k) route. This phase of work will not include any animal or human testing. PHASE III: In this phase, any additional changes from customer feedback will be incorporated into the design, and the initial drug to be supplied to the DoD in the injector system will be selected. A detailed data package will be developed for submission to the FDA for approval of the autoinjector platform or the autoinjector platform/drug combination suitable for administration of CBT therapeutics. Once this compact and robust autoinjector platform is approved by the FDA, it could be filled with other pharmaceutical compounds that would benefit civilian markets such as diabetes care, pain management, and large-molecule drug delivery. PHASE III DUAL USE APPLICATIONS: A compact, easy-to-use, and temperature tolerant autoinjector would serve the commercial market for drug injection. For example, thermally stable vaccines, pre-loaded into the injection platform, could have value to rapidly control outbreaks worldwide and would eliminate the need for intermediate steps to include drug reconstitution and manual mixing, along with the need for a high-value medical professional. REFERENCES: 1. MicroElectroMechanical Systems (MEMS): http://mems.sandia.gov/ 2. Potyrailo, R.A.,"Chemical Sensors: New Ideas for the Mature Field,""Functional Thin Films and Nanostructures for Sensors,"Ed: Zribi, A and Fortin, J., ISBN: 9780387686097, Springer US, 2009, pp 103-143 3. New blood analysis chip could lead to disease diagnosis in minutes: http://newscenter.berkeley.edu/2011/03/16/standalone-lab-on-a-chip/ 4. Luttge, R.,"Chapter 8 Microfabrication for Novel Products in Drug Delivery: An Example,""Microfabrication for Industrial Applications,"ISBN: 9780815515821, Elsevier, 2011, Pages 235272
