the pennsylvania state university ota symposium€¦ · nucleic acid, protein, polysaccharide,...

COL David HammerJoint Project Manager Medical Countermeasure Systems

The Pennsylvania State University OTA Symposium

BUILDING THE CBR DIAGNOSTIC FAMILY OF SYSTEMS

UNCLASSIFIEDDistribution Statement A:

Approved for public release; distribution

is unlimited.

January 15-16, 2019

PROTECTING THE JOINT FORCE

20190115 PSU BriefUNCLASSIFIED 2

DEPARTMENT OF DEFENSE


Chemical Biological Defense Program

JOINT PRODUCT LEAD (JPDL) DIAGNOSTICS (DX)JPdL Diagnostics Mission

• Develop, acquire, integrate, and field identification technologies and Food and Drug Administration (FDA)-cleared diagnostic systems for the Warfighter and the Nation to aid in the diagnosis, prevention, and treatment of the effects of exposure to chemical, biological, and radiological (CBR) threats.


Presenter

Presentation Notes

DOD ROLES OF CARE

Combat Zone

ROLE 1: FIRST RESPONDER

ROLE 2: FORWARD

RESUSCITATIVE CARE

Aircraft CarrierLHA/LHD

ROLE 3: THEATER

HOSPITALIZATION

Theater Hospital

Mobile Forward Surgical Team

Expeditionary Medical Support

Aircraft CarrierFleet Surgical TeamLHA/LHD

SubmarineSurface

Combatant ShipsLSD/LPD

LSD / LPD

Submarine

Medical Treatment

Facilities Hospitals

Joint Base

Medical Evac

Forward Support Medical Company

BattalionAid Station

Combat Support Hospital

Decontamination

Shock Trauma PlatoonMedical Battalion Surgical

Expeditionary Medical Support

Forward Surgical Team

Decontamination

Combat Medic/Lifesaver

CHEM or BIO Incident

ROLE 4: DEFINITIVE

CARE

Medical Evac Vehicle

Treat & Return to

DutyTreat,

Stabilize & Expedite

Treat & Specialized Evacuation

Quarantine


BREADTH AND DEPTHNotional End State

• Breadth: Total menu of diagnostic capabilityo Full breadth of coverage = diagnostic capability for all possible CBR threats

• Depth: The lowest role of medical care where a diagnostic test is clinically and operationally suitable

Breadth

Depth

Role 3

Role 2

Role 1

Bio Chem Rad

Fielded capability

Capability in development

No capability


FAMILY OF SYSTEMSFamily of Systems concept

• A suite of diagnostic instruments and assays capable of diagnosing the full breadth of threats at all necessary roles of care

o No single technology will be capable of diagnosing all CBR-related diseaseNucleic acid, protein, polysaccharide, enzyme activity, small moleculeQualitative, quantitativeClinical sample type considerations

o No single instrument will be suitable for use at every role of careSize and weightPower ThroughputComplexity


NEXT GENERATION DIAGNOSTIC SYSTEM INCREMENT 1

8

NGDS INCREMENT 1Program Goals

• Improve Biological Warfare Agent (BWA) diagnostic and detection capability

o Support clinical diagnosis to inform patient treatment decisionso Support Force Health Protection decision makingo Augment CBRN situational awareness

• Reduce overall complexity of diagnostic tests• Integrate CBRN diagnostics with everyday medical practice• Encourage development of additional panels of military

significance


NGDS INCREMENT 1 SYSTEM

• FilmArray 2.0 instrument• Loading station• Ruggedized GETAC laptop computer• Hardened reusable shipping case• DOD-funded BWA Warrior Panel• DOD-funded Sentinel Panel


DOD-FUNDED FILMARRAY PANELS

Warrior Panel Sentinel Panel(FDA-cleared) (Environmental identification)

Bacterial targetsBacillus anthracisYersinia pestisFrancisella tularensisCoxiella burnetiiViral TargetsEbolavirus

Zaire ebolavirusSudan ebolavirusBundibugyo ebolavirusTai Forest ebolavirusReston ebolavirus

MarburgvirusMarburg virusRavn virus

Bacterial targetsBacillus anthracisBurkholderia spp.Burkholderia pseudomalleiCoxiella burnetiiFrancisella tularensisBrucella spp.Brucella melitensisRickettsia prowazekiiViral targetEbolavirus

Zaire ebolavirusSudan ebolavirusBundibugyo ebolavirusTai Forest ebolavirusReston ebolavirus

MarburgvirusMarburg virusRavn virus

Orthopox virusesVariola virusVenezuelan Equine Encephalitis virusWestern Equine Encephalitis virusEastern Equine Encephalitis virus

Toxin gene targetsClostridium botulinumRicin communisTraining targetsBacillus globigiiBacillus thuringiensisSaccharomyces cerevisiae


WARRIOR PANELIntended Use StatementThe FilmArray NGDS Warrior Panel is a qualitative, multiplexed, nucleic acid-based in vitro diagnostic test intended for use with the FilmArray 2.0 system. The FilmArray NGDS Warrior Panel detects and identifies Bacillus anthracis, Yersinia pestis, Francisella tularensis, Coxiella burnetii, Ebola virus, and Marburg virus nucleic acids directly from human whole blood (EDTA). The FilmArray NGDS Warrior Panel is also intended to be used to test for Bacillus anthracis or Yersinia pestis nucleic acids in blood cultures that are determined to be positive either by an automated system, by turbidity, or by daily Gram stain even without turbidity, and is indicated to be performed with concomitant Gram stain performed on positive blood culture specimens as per normal laboratory procedure. In addition, the FilmArray NGDS Warrior Panel may also be used to detect and identify Yersinia pestis and Francisella tularensis nucleic acids directly from sputum specimens.

The FilmArray NGDS Warrior Panel is intended to test individuals with signs and symptoms of infection from biothreat agents and/or individuals who are at risk for exposure or may have been exposed to these agents.

The FilmArray NGDS Warrior Panel is indicated as an aid in the diagnosis of anthrax, plague, tularemia, Q fever, and the hemorrhagic fevers caused by Ebola and Marburg viruses, in response to a suspected or confirmed bioterrorism event or outbreaks. It is for diagnostic use in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the appropriate Department of Defense and public health authorities.

Results are for the presumptive identification of Bacillus anthracis, Yersinia pestis, Francisella tularensis, Coxiella burnetii, Ebola virus, and Marburg virus. The definitive identification of Bacillus anthracis, Yersinia pestis, Francisella tularensis, Coxiella burnetii, Ebola virus, and Marburg virus requires additional testing and confirmation procedures in consultation with the appropriate Department of Defense and public health authorities for whom reports may be necessary. Negative results do not preclude infection with these biothreat agents and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

The FilmArray NGDS Warrior Panel is solely for use by United States Department of Defense laboratories, and laboratories designated by the Department of Defense.


NEXT GENERATION DIAGNOSTIC SYSTEM 2

13

NGDS INCREMENT 2Program Goals

• Expand the breadth and depth of CBRN diagnostics o Breadth: Total menu of diseases (Diagnostics beyond Polymerase Chain

Reaction (PCR))o Depth: Moving the tests closer to the point-of-need when both

operationally and clinically supportable

• Integrate CBRN diagnostics with everyday medical practiceo Routine healthcare testing (e.g. clinical chemistries)o Endemic infectious disease

• Seek Interim Fielding Capabilities (IFC): Pre-Emergency Use Authorization

• Complementary to NGDS Increment 1 (FilmArray)


NGDS INCREMENT 2 MATERIEL SOLUTIONS

• NGDS Increment 2 is exploring multiple materiel solutions to expand the breadth and depth of CBRN diagnostics

o Man Portable Diagnostic System (MPDS)Addresses BW diagnostic gaps at lower roles of care (Role 1-2)

o Chemical Diagnostic (ChemDx)- organophosphate nerve agents Improved suitability relative to currently fielded EQM Test-mate diagnosticAddresses diagnostic gaps at lower roles of care (Role 1-2)


MAN PORTABLE DIAGNOSTIC SYSTEM

• U.S. Special Operations Command (USSOCOM)o Small-team users with limited reach back to supportive care

Austere environments, outside of fixed laboratory (carried in)24-72 hours from definitive medical careUnnecessary evacuation creates mission impactsResources limited to what the team has locally, but users are highly trained

• Requirementso FDA cleared for use by appropriately trained personnelo Portable: Less than 5 lbs., fits in a backpack (<300 in3)o Durable: Operable in a range of environmental conditionso Powered: Battery operable/rechargeable, 5 or more runs/charge desiredo Stable: Consumables stable at Room Temperatureo Simple: Clinical Laboratory Improvement Amendments (CLIA) waived or

equivalent o Timely: Actionable result returned in <70 minutes


MAN PORTABLE DIAGNOSTIC SYSTEMPotential Solutions

• Funding two candidate deviceso Cepheid GeneXpert Omni, Biomeme Three9 Dx

• Diagnostic Panelso Panel 1: Malaria, Dengue, Chikungunya, Zika, Leptospirosis

o Inclusion of Leptospira dependent on performance in capillary blood

o Panel 2: Ebola, Marburg, Lassa, CCHF o Panel 3: Virus vs. Bacteria Differentiation, host-response testo Panel 4: Bacterial Biothreat; agents dependent on final requirements from the Joint Services


CHEMDXA Chemical Intoxication In Vitro Diagnostic

A low-cost, portable, rapid diagnostic of chemical warfare agent exposure that is easy to use and operationally suitable for battlefield environments.• In Vitro Diagnostics (IVD) of clinically-relevant

acetylcholinesterase (AChE)-inhibitiono Effective pre- and post-symptomaticallyo Low-to-high exposures o Variety of cholinesterase inhibiting agentso FDA clearance by 4QFY21

• Improved suitability for farther forward than Role 3o Austere battlefield environmentso Simple operation (CLIA-waivable)

• Alleviate need for previously-recorded, patient-specific baseline


TODAY’S CBR DIAGNOSTIC LANDSCAPE

Breadth

Depth

Role 3

Role 2

Role 1

Bio Chem Rad

Fielded capability

Capability in development

No capability


FUTURE DIRECTIONS AND OPPORTUNITIES

• Simpler, Faster, Smallero Improved operation suitabilityo Reduced training, reduced logistics burden, improved lifecycle sustainment

• Genomic Sequencingo Targeted sequencingo Agnostic sequencing

• Wearable Technologieso Real-time monitoring of Soldiers health

• Host Based Marker Discovery and Validationo Diagnosis of disease syndromeso Earlier disease diagnosiso Better inform operational medical decision making


The right technology,at the right time,in the right place and for the right cost.

Jason Opdyke, PhDJoint Product Lead (Acting), DiagnosticsMedical Countermeasure Systems

[email protected]

21

BACKUP

22

BIOFIRE DIAGNOSTICS COMMERCIAL PANELS

Respiratory Panel

Blood Culture Identification

Gastrointestinal Disease Panel

Meningitis/Encephalitis Panel

(FDA Cleared) Panel (FDA Cleared) (FDA Cleared) (FDA Cleared)Viral TargetsAdenovirusCoronavirus HKU1Coronavirus NL63Coronavirus 229ECoronavirus OC43Human MetapneumovirusHuman Rhinovirus/EnterovirusInfluenza AInfluenza A/H1Influenza A/H3Influenza A/H1-2009Influenza B*

Parainfluenza Virus 1Parainfluenza Virus 2Parainfluenza Virus 3Parainfluenza Virus 4Respiratory Syncytial VirusBacterial targetsBordetella pertussis, Chlamydophila pneumoniaeMycoplasma pneumonia

Gram + Bacterial targetsEnterococcusListeria monocytogenesStaphylococcusStaphylococcus aureusStreptococcusStreptococcus agalactiaeStreptococcus pyogenesStreptococcus pneumoniae

Gram – Bacterial targetsAcinetobacter baumanniiHaemophilus influenzaeNeisseria meningitidisPseudomonas aeruginosaEnterobacteriaceaeEnterobacter cloacae complexEscherichia coliKlebsiella oxytocaKlebsiella pneumoniaeProteusSerratia marcescens

Fungal targetsCandida albicansCandida glabrataCandida kruseiCandida parapsilosisCandida tropicalis

Antibiotic Resistance targetsmecA – methicillin resistantvanA / vanB – vancomycin restitantKPC – carbapenem resistant

Bacterial targetsCampylobacter (jejuni, coli, and upsaliensis)Clostridium difficile (toxin A/B)Plesiomonas shigelloides Salmonella Yersinia enterocolitica Vibrio (parahaemolyticus, vulnificusand cholera)Diarrheagenic E. coli/ShigellaEnteroaggregative E. coli (EAEC)Enteropathogenic E. coli (EPEC)Enterotoxigenic E. coli (ETEC) lt/stShiga-like toxin-producing E. coli (STEC) stx1/stx2E. coli O157Shigella/Enteroinvasive E. coli (EIEC)

Viral targetsAdenovirus F40/41 Astrovirus Norovirus GI/GII Rotavirus A Sapovirus (I, II, IV and V)Parasitic targetsCryptosporidium Cyclospora cayetanensis Entamoeba histolytica Giardia lamblia

Bacterial targetsEscherichia coli K1Haemophilus influenzaeListeria monocytogenesNeisseria meningitidisStreptococcus agalactiaeStreptococcus pneumoniae

Viral targetsCytomegalovirus (CMV)EnterovirusEpstein-Barr virus (EBV)Herpes simplex virus 1 (HSV-1)Herpes simplex virus 2 (HSV-2)Human herpesvirus 6 (HHV-6)Human parechovirusVaricella zoster virus (VZV)

Fungal targetsCryptococcus gattiiCryptococcus neoformans


CHALLENGES TO SUCCESS

• Limited understanding of Molecular Pathology of diseaseso What markers are predictive of disease? (agent or host)o When do markers appear during disease course?o Where do markers accumulate? (sample types)

• Technologyo Operational suitability: Commercial Off the Shelf (COTS) or DoD specifico When to “buy in” to a technology?

• Concept of Operations (CONOPS)o Understanding how a test can be used in a deployed environment to

improve patient outcomes and operational decision making

• Regulatoryo Maintaining regulatory compliance in unconventional use scenarios


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