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Field Portable Mass Spectrometry for Small Molecule Drugs in Clinical Samples

Description:

TECHNOLOGY AREA(S): Chem Bio_defense, Bio Medical 

OBJECTIVE: To provide a rapid, easy to use method for human clinical sample testing that is effective for the detection and identification of novel designer drug combinations in non-traditional sample types. Capabilities sought should encompass the end-to-end method to include low invasive clinical sample collection and be suitable for use in a field environment. Desired end-state is an U.S. Food and Drug Administration (FDA) cleared in vitro diagnostic device, but interim phases of capability development, to include environmental sample types and data sets sufficient for a Government supported Emergency Use Authorization submission, are acceptable. 

DESCRIPTION: The U.S. Department of Defense (DoD) requires the capability to rapidly assess Warfighter exposures to a rapidly evolving range of drugs that affect the central nervous system (e.g., anesthetics, sedatives, analgesics, etc.) and, furthermore, to monitor the efficacy of medical countermeasures throughout the course of patient treatment. Current mass spectrometry instrumentation for drugs-of-abuse testing are fragile, bulky, heavy, and expensive, while methods often rely upon volunteered clinical urine samples. Furthermore, although there are many commercially available, portable, field-rugged mass spectrometers, none were developed or produced within a regulatory framework supporting future FDA-regulated applications and nor include end-to-end analytical methods suitable for the intended use in field environments. Immunoassay-based approaches (such as lateral flow immunoassays) may not have sufficient inclusivity, specificity, or sensitivity and involve a development pathway too long to keep pace with the rapidly emerging and evolving novel compounds and mixtures of concern. This topic seeks to develop novel approaches to provide practical patient diagnostics and screening capabilities at field deployment locations from least-invasive clinical sample types while maintaining desirable operational suitability characteristics. Sample types that may be collected rapidly under any condition immediately after suspected exposure or from non-ambulatory personnel are essential (e.g., capillary blood, saliva, etc.) and appropriate pairing to the mass spectrometer sample inlet method (e.g., solid-phase microextraction, paper spray ionization) is a requirement. Incorporation of semi-automated capillary blood sample collection tools into the analytical method (i.e. arm stick collection devices) would further enhance operator safety and ease of use when wearing personal protective equipment. The topic may be inclusive of the development of a new mass spectrometer intended for the diagnostic market or the incorporation of an existing instrument into a new method and medical device. 

PHASE I: Demonstrate efficacy, within a laboratory environment, of new methodology and/or instrumentation or instrument modifications/integration for mass spectrometry-based assays for the detection and identification of novel designer drug combinations that affect the central nervous system (e.g., anesthetics, sedatives, and analgesics) in non-traditional sample types simulating those which could be collected in a minimally invasive manner from exposed humans (e.g., capillary blood and saliva) and prepared in a field environment. Provide experimental evidence indicating the potential for this assay to be applied effectively using either existing, modified, or novel field-rugged mass spectrometry systems. Use of human or animal subjects is not intended, or expected, in order to establish/achieve the necessary proof-of-concept in Phase I. 

PHASE II: Develop initial small molecule compound libraries suitable to the analytical method. Demonstrate the end-to-end analytical method, relative to the device maturity, sufficient to indicate the operational suitability of the final device and method for the intended operational environment. Demonstrate efficacy using contrived surrogate samples or from an appropriate animal exposure model. Develop an in vitro diagnostic Target Product Profile and, relative to the maturity of the device, develop and submit a U.S. FDA pre-submission application describing the proposed regulatory approach for FDA clearance. PHASE III: Complete device analytical method development and transition to full-rate manufacturing under current Good Manufacturing Practices (cGMP). Conduct reliability and ruggedness qualification testing appropriate to the intended operational environment. Conduct analytical studies and clinical trials to support a de novo or 510(k) submission. Expand the compound library and range of analytical methods to additional defense and dual use environmental, medical surveillance, and diagnostic applications. 

PHASE III: PHASE III: Complete device analytical method development and transition to full-rate manufacturing under current Good Manufacturing Practices (cGMP). Conduct reliability and ruggedness qualification testing appropriate to the intended operational environment. Conduct analytical studies and clinical trials to support a de novo or 510(k) submission. Expand the compound library and range of analytical methods to additional defense and dual use environmental, medical surveillance, and diagnostic applications. PHASE III DUAL USE APPLICATIONS: Potential alternative applications include drug enforcement applications within the civilian sector and the protection of law enforcement and laboratory personnel. 

REFERENCES: 

1: CLIA Categorizations (n.d.), retrieved December 2nd, 2014 from http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/IVDRegulatoryAssistance/ucm393229.htm

2:  Field Manual 4-02 Army Health System, August 26th 2013, retrieved Dec 17th from http://armypubs.army.mil/doctrine/DR_pubs/dr_a/pdf/fm4_02.pdf , pages 1-9, 7-7 and 7-8

KEYWORDS: Mass Spectrometry, Opioid, Fentanyl, Designer Drugs, In Vitro Diagnostic, Point Of Care, Small Molecule 

CONTACT(S): 

Adam Becker 

(240) 409-7596 

adam.j.becker3.civ@mail.mil 

Brian Pate 

(703) 767-4894 

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