Bio Defense Research Supporting the Dod a New Strategic Vision Pub767

8/7/2019 Bio Defense Research Supporting the Dod a New Strategic Vision Pub767

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BIODEFENSE RESEARCHSUPPORTING THE DoD:

A NEW STRATEGIC VISION

Coleen K. Martinez

March 2007

This publication is a work of the U.S. Government as denedin Title 17, United States Code, Section 101. As such, it is in thepublic domain, and under the provisions of Title 17, United StatesCode, Section 105, it may not be copyrighted.

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*****

The views expressed in this report are those of the authorand do not necessarily reect the ofcial policy or position of theDepartment of the Army, the Department of Defense, or the U.S.Government. This report is cleared for public release; distributionis unlimited.

*****

This report is modied from its original text to comply withDepartment of Defense operational security requirements forpublication in the open literature. Authorized individuals mayrequest an unmodied version of this publication by contactingCommander, U.S. Army Medical Research and MaterielCommand, Attention: MCMR-SGS, 504 Scott Street, Fort Detrick,Maryland 21702-5012.

*****

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ISBN 1-58487-288-8


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FOREWORD

The general public often assumes that medical productswill be available to members of the U.S. armed forces inharms way. Availability of safe and effective drugs andvaccines, however, is never an accident; such products arethe fruition of focused and methodical research, testingand evaluation over many years. Medical research isinherently a high risk endeavor, and even the most efcient

programs can span almost 15 years and cost over $1 billionfrom product discovery to Food and Drug Administrationlicensure.

In this monograph, Colonel Coleen Martinez examinesthe productivity of the Department of Defenses biodefenseresearch program over the course of more than 35 years,coupled with changes in the global research environmentsince the events of September 11, 2001. Few will arguethe need for a national investment in biodefense. Wherethe deployment of a biologic agent of mass destruction islargely an unpredictable risk, the outcome certainly couldbe catastrophic for an unprotected population. An urgentmoral imperative is cast upon the federal government,then, to objectively assess the application and managementof its biodefense research resources.

The purpose of this monograph is not to providea single solution, but rather to stimulate senior leader

critical analysis, dialogue and action to improve programefciency and productivity for the benet of both thewarghter and the nation. The Strategic Studies Instituteis pleased to publish it as a contribution to the debate onthis important subject.

DOUGLAS C. LOVELACE, JR.DirectorStrategic Studies Institute


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BIOGRAPHICAL SKETCH OF THE AUTHOR

COLEEN K. MARTINEZ, a colonel in the U.S. Army, iscurrently assigned as the Director of Medical Systemsfor the U.S. Army Medical Research and MaterielCommand with duty at the Ofce of the AssistantSecretary of the Army for Acquisition, Logistics, andTechnology in the Pentagon. She has held a varietyof positions within both clinical and medical researchenvironments, and has deployed in support of medicaloperations in Bosnia, Kuwait, and Iraq. She is LevelIII certied in Program Management through theDefense Acquisition University. Colonel Martinezwas commissioned into the Medical Service Corps in1981 as an ROTC Distinguished Military Graduateupon earning a Bachelor of Science degree in Medical

Technology from Lake Superior State College. She isa graduate of the U.S. Army's Command and GeneralStaff College and the U.S. Army War College, andholds a Master of Strategic Studies from the Army WarCollege and a Ph.D. in Immunology from VirginiaCommonwealth University.


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SUMMARY

The Department of Defense (DoD) has had aunique mission in biological defense research overthe past 4 decades. Throughout this history, themilitary biological disease threats were relativelystraightforward, there was little urgency linked tosuccessful product elding, there was no mechanismby which to gain Food and Drug Administration (FDA)product licensure, and there was little competitionfor mission or funds. In the post-September 11, 2001(9/11) environment, however, the scope of potentialthreats has increased immeasurably, relative fundingfor the DoD has decreased, urgency to eld solutionshas skyrocketed, the FDA has provided a way forwardto product licensure, and active non-DoD players

in this arena have grown exponentially, aligningwith newly designated, congressionally mandatedfunding sources. The old paradigms that governedthe DoD research program structure and mission areno longer viable in this changing environment. Thismonograph examines the current organization ofthe DoD biodefense research program in light of thechanging national biodefense landscape and industrybest practices, and argues that all aspects of the DoDbiodefense program should be consolidated with allother federal biodefense resources, including thosewithin the National Institutes of Health, to create asingle, focused, and productive program. This newagency, subordinate to the Department of Health andHuman Services, will be positioned and equipped to

provide medical solutions to the warghter on thebattleeld, as well as to U.S. citizens.


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BIODEFENSE RESEARCHSUPPORTING THE DoD:

A NEW STRATEGIC VISION

INTRODUCTION

He who every morning plans the transaction of the dayand follows out that plan, carries a thread that will guidehim through the maze of the most busy life. But where

no plan is laid, where the disposal of time is surrenderedmerely to the chance of incidence, chaos will soon reign.

Victor HugoFrench dramatist, novelist,and poet (1802-85)

Since President Richard M. Nixon declared the end ofthe U.S. offensive biological research program in 1969,1the U.S. Department of Defense (DoD) has pursued aresearch program strictly for defensive purposes, withthe primary objective being development of productsto protect the warghter on the battleeld. DoD,after almost 4 decades of investment in a biologicaldefense program, has contributed signicantly to the

scientic knowledge base and has produced morethan two dozen candidate pharmaceutical products.Three of these candidates are currently in advanceddevelopment within the DoD, some have been assumedby the National Institute of Allergy and InfectiousDisease (NIAID) for further development, severalare no longer being developed and are available foruse only as Investigational New Drugs (INDs, alsoreferred to as investigational), several have beendropped completely from development, and severalstill languish in the technical scientic base awaiting aDoD decision on further investment.2


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Gaining Food and Drug Administration (FDA)licensure of products is a difcult task, requiring

demonstration of the products safety and effectivenessfor the stated indication of use. Before 2002, licensingbiodefense pharmaceutical products was an impossibletask because, for obvious reasons, it was unethicalor impracticable to conduct human clinical trials forefcacy. Such testing required challenging a personwho had received the developmental medical productwith a biological threat agent to demonstrate that theproduct actually prevented or treated the disease.Recognizing this barrier to licensure, and coincidentwith a heightened need for biodefense preventiveand therapeutic countermeasures, the FDA approvedthe animal rule in 2002.3 The animal rule allows forlicensure in the absence of human efcacy testing, if atleast one (more likely two) surrogate animal models

faithfully representing human infection and diseasecaused by the authentic biological agent are availableand provide sufcient data to suggest that the productwill act similarly in humans.

Approval of the animal rule by the FDA was criticalto DoD, since only 4 years earlier, in the midst of GulfWar Syndrome concerns, DoD had been cited in aGovernment Accounting Ofce report with numerousdeciencies in its ability to administer investigationalproducts (products approved only for testing inhumans and not yet licensed by the FDA for generaluse) in an operational environment.4 Subsequently, inresponse to both safety and public perception concernsregarding DoDs use of investigational products inservice members, the Deputy Secretary of Defense

directed DoD to use licensed products preferentiallyover investigational products, and ruled that apresidential waiver was required in the event that an


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investigational product was to be used in the absenceof an obtained informed consent.5 Aligning with these

events, the medical biodefense mission appeared to beclear: develop FDA-licensed medical countermeasuresto protect the warghter from biological warfarethreats.

The faltering productivity of the DoD biodefenseprogram, despite its world-class infrastructure,talented workforce, and well-dened acquisitionframework, appears to be directly related to itsconvoluted, unnecessarily complex, and circuitouschains of authority with regard to pharmaceuticaldevelopment coupled with insufcient management,oversight, and accountability. Similarly, U.S. scalresources increasingly are poured into non-DoDmedical biodefense research without any overarchingplans to orchestrate these investments into licensed

products. The nation requires a clean excision of allmedical biodefense resources from within the federalgovernment and consolidation under a new agencybirthed specically to support efcient productdevelopment.

CHALLENGES OF PHARMACEUTICALDEVELOPMENT

The Industry Model.

Development of pharmaceutical products is along, complex process. Industry, including smallbiotechnology companies, out of necessity, hasbeen most efcient at dening and negotiating the

pathway of medical product discovery, development,and acquisition. Even using best business practices,however, the average timeline from discovery toFDA licensure currently is 14 years6 and requires an


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investment between $800 million (M) and $1.6 billion(B) per product.7 One of the most signicant total-

cost drivers for development is the high number ofcandidate failures for each successfully developed andmarketed product, reecting the technical risk inherentin pharmaceutical product research.

The major elements of product development arecandidate discovery; preclinical studies (laboratoryand animal); clinical trials (human safety andhuman or animal efcacy); product manufacturing,characterization, and release; and FDA IND andlicensure submissions. One estimate describes apathway beginning with 10,000 candidates, of which250 succeed in entering preclinical studies, of whichonly ve make it to late-stage clinical trials, after whichone passes the stringent licensing requirements.8 Themost effective way to reduce both the timeline and

cost associated with nding the winning product is tomanage the development closely and to identify thefailures and discontinue those efforts as early in theprocess as possible, so that resources can be refocusedon the remaining contenders.9

Industry Management.

The issue of identifying and abandoning losingcandidate products early is extremely important, butnot simple. There is a ne balance between killing apromising candidate too early, when perhaps someretooling could have transformed it into a success,versus the temptation to continue to pour resourcesinto a candidate that is failing in the hope that it can be

revived. These difcult management decisions requireprogram leaders who are qualied and experiencednot only in the science to understand the technicaldata and appropriately interpret the risks, but also in


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pharmaceutical and business acquisition requirements,to corporately assess the approach from a programmatic

perspective.Industry best practice places a single empowered

and accountable individual (project manager) in chargeof the program and ensures focused [not diffuse]cross-functional management . . .10 The corporateexecutives empower interdisciplinary managementteams who are charged to meet prospective and well-dened milestones, and who are given the exibilityto manage their resources (e.g., personnel and budget)to attain their goals. To earn this exibility, the teamsare held accountable to meeting their milestones andare rewarded for success. In the technology base,higher-level management reviews typically occur ona quarterly basis.11 The straightforward managementchain and minimal layers from the highest position

down to the lowest echelon of operations are apparentin Figure 1.

Figure 1. Simplifed Organizational Chart Depictinga Generic Industry Model for a PharmaceuticalCompany Dedicated to Vaccine Development.


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CHALLENGES OF THE DoD BIODEFENSEACQUISITION SYSTEM

Leadership.

Congress, over the last decade, has questioned themanagement and productivity of the DoDs biodefensemedical product-development program. Congressionalconcerns have led to a number of commissionedstudies by panels of national pharmaceutical experts toanalyze the DoD system and proffer recommendationsfor decreasing development risk and improving efci-encies and success rates.12 It is puzzling that despite therepeated emergence of common themes in the studyoutcomes such as recognition of disjointed andineffective management13 and an organizationalstructure that is unnecessarily complex and counter-

productive14

and quite explicit recommendations withregard to the same, the DoD has not improved theresearch and development program substantially inaccordance with any of these recommendations. SuchDepartment nonresponsiveness in the face of clearcongressional intent to address risk reduction in anextremely high-priority program area leads the authorto believe the only explanation is that the recommendedsolutions are too hard to do. The DoD is like thegiant sloth, too large, heavy, and slow to be able totransform its structure and processes. The sloth movesvery slowly and only if necessary;15 similarly, therehas been no compelling reason for the DoD to chooseto move to improve its biodefense medical productdevelopment program substantially, because, despite

its lack of response, its programs continue to receivefunding. One signicant obstacle is that many key DoDleadership positions lack individuals knowledgeable


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in, and appreciative of, the complexities of medicalproduct development. Although many recent strategic

documents stress the critical importance and highpriority of the biodefense program,16 there appears tobe a tacit acceptance that once the leaders validate theprograms criticality, then a miracle will occur andlicensed products will begin to appear. Without anappreciation of the structure and management changesnecessary to improve efciency and effectiveness inthis complicated and lengthy endeavor, there is noimpetus for the wholesale transformation, which theexperts deem as indispensable to an effective program.The high priority assigned to the DoDs biodefenseresearch program wanes when the leaders are facedwith difcult decisions with regard to organizationand resourcing.

Management.

As referenced above, a repeated criticism of the DoDbiodefense program is its fragmented organizationalstructure. In contrast to the streamlined industrymodel previously illustrated in Figure 1, the DoDsresearch and development structure is complex anddiffuse, with many stakeholders. Before 2004, theArmy as executive agent bore primary responsibilityfor managing and executing the DoDs biodefenseprogram. The Army Medical Department Centerand School had responsibility for requirements, the Joint Services Management Group had oversight ofproducts, and the Joint Program Executive Ofcer forthe newly-formed Joint Program Executive Ofce for

Chemical and Biological Defense (reporting throughthe Army Acquisition Executive to the DefenseAcquisition Executive) managed the chemical andbiological material acquisition process.


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The Defense Advanced Research Projects Agency(DARPA) additionally devoted signicant funding to

medical biodefense discovery efforts (ranging fromover $60M in Fiscal Year (FY)01 to $45M in FY0417), butthere was no mandate to coordinate these projects with,or to feed their outcomes into, the Armys biodefenseprogram. There was a limited DARPA program fromFY01-05 in which approximately $40M of funds wasavailable to support transition of candidate productsinto more mature development efforts.18 Thesetransition funds were awarded competitively by theDoD to extramural research contracts, however, withnone designated for intramural use to seed initiationof potential new programs borne of successful DARPAprojects. The net result of this 5-year investment hasbeen no integration of any promising DARPA effortsinto the DoDs medical acquisition system.19

Nonpharmaceutical biodefense research efforts,such as those developing personal protectiveequipment and sensors, fell directly under the UnderSecretary of Defense for Acquisition, Technology, andLogistics, and were managed by the Defense ThreatReduction Agency. Fueled by concerns that programswere not coordinated and integrated sufciently,the Under Secretary of Defense for Acquisition,Technology, and Logistics directed the Assistant tothe Secretary of Defense (Nuclear and Chemical andBiological Defense Programs) to assign responsibilityfor management and integration of all CB Science andTechnology efforts . . . to the Defense Threat ReductionAgency in 2002.20 Despite good intentions, thissolution exacerbated the fragmentation of the program

management by reinforcing a chasm between the DoDstechnology base and advanced development stages ofthe program. This management change also openedthe technology base beyond the DoDs laboratories


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to allow any organization performing biodefenseresearch to compete for funding and eventual entry

of its candidate product into the DoD acquisitionsystem. Effectiveness of implementing this potentiallypositive change, however, was tempered by the lack ofany overarching development plans. The net impact,therefore, was dilution of program scal resourcesacross a larger candidate base, still without a plan tofocus and follow-through on specic candidates (DoDor non-DoD).

The issue of fragmented organizational programstructure was cited as a signicant obstacle to programsuccess in program evaluations such as the Report of aPanel of Experts in 200021 and the Institute of MedicineReport on DoD Vaccine Acquisition in 2002.22 Basedon an unwieldy program structure (Figure 2),23 theInstitute of Medicine study panel recommended

consolidating all DoD elements conducting medicalbiodefense research. The DoD indeed did respond tothe recommendations, as subsequently mandated byCongress, by extracting all elements of the programpreviously managed by the Army as lead agent forthis effort and relocating them under the DoD ofcesfor program management and direction (Figure3).24 The congressional intent spanned beyond themedical biodefense program and was an attempt toconsolidate all medical and nonmedical aspects of theprogram, bringing them under common oversight. Thecongressional mandate did, in fact, bring aspects ofbiodefense medical and non-medical programs underDoD oversight, but in so doing had the untowardsecondary effect of creating an even more diffuse and

convoluted management system for pharmaceuticaldevelopment. Instead of streamlining the structure,this reorganization only served to move drug andvaccine development further away from the industrybest practices model.


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USD(P&R)

ASD(HA)

USD(AT&L)

DCSOPSDDR&E

DATSD (CBD)

JNBCDB

DTRA

CBD

CJCSSEC ARMY

SECDEF

Army SG AAE

AMEDD C&S

USAMRIID

USAMRMC

MBDRP

WRAIR USAMMDA JSIG

JSMG

DARPA

= Members of CSD CB Defense Steering Committee

= Significant impact on Biodefense Program

= Coordination/Oversight

AAE, Army Acquisition Executive;AMEDD C&S, Army Medical Department Center and School;Army SG, Army Surgeon General;ASD(HA), Assistant Secretary of Defense for Health Affairs;CBD, Director Chemical Biological Directorate;CJCS, Chairman, Joint Chiefs of Staff;DARPA, Defense Advanced Research Projects Agency;DATSD(CBD), Deputy Assistant Secretary of Defense, Chemical andBiological Defense Programs;DCSOPS, Deputy Chief of Staff for Operations;DDR&E, Director of Defense Research and Engineering;DTRA, Defense Threat Reduction Agency;JSIG, Joint Service Integration Group;JSMG, Joint Service Materiel Group;

MBDRP, Medical Biological Defense Research Program;SEC ARMY, Secretary of the Army;SECDEF, Secretary of Defense;USAMMDA, U.S. Army Medical Materiel Development Activity;USAMRIID, U.S. Army Medical Research Institute of InfectiousDiseases;USAMRMC, U.S. Army Medical Research and Materiel Command;USD(AT&L), Under Secretary of Defense for Acquisition, Technologyand Logistics;USD (P&R), Under Secretary of Defense for Personnel and Readiness;WRAIR, Walter Reed Army Institute of Infectious Diseases.

Figure 2. Simplifed Organizational Chart DepictingDoD Biodefense, Pre-2004.


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= Significant impact on Biodefense Program

= Coordination/Oversight

* Assigned responsibility for centralized oversightof nuclear, chemical and biological defenseprograms medical and non-medical.

** Directs PPB for all DoD biodefense research.

SECDEF

USD(P&R) SEC ARMY USD(AT&L) CJCS

ASD(HA)

MCDRP

MIDRPUSAMMDA

AAE ATSD* DARPA JRO-CBRN**

USAMRMC JPEO-CBD DTRA DATSD(CBD)

USAMRIID MBDRP CBMS CBD

WRAIR JVAP MITS

DVC

MEDCOM(Army SG)

AAE, Army Acquisition Executive;AMEDD C&S, Army Medical Department Center and School;Army SG, Army Surgeon General;ASD(HA), Assistant Secretary of Defense for Health Affairs;ATSD, Assistant to the Secretary of Defense;CBD, Director Chemical Biological Directorate;CBMS, Chemical Biological Medical Systems;CJCS, Chairman, Joint Chiefs of Staff;DARPA, Defense Advanced Research Projects Agency;

DATSD(CBD), Deputy Assistant Secretary of Defense, Chemical andBiological Defense Programs;DCSOPS, Deputy Chief of Staff for Operations;DDR&E, Director of Defense Research and Engineering;DTRA, Defense Threat Reduction Agency;DVC, Dynport Vaccine Company (DoD prime systems contractor);JRO-CBRN, Joint Requirements Ofce for Chemical, Biological,Radiological and Nuclear Defense;JVAP, Joint Vaccine Acquisition Program;MBDRP, Medical Biological Defense Research Program;

MCDRP, Medical Chemical Defense Research Program;

Figure 3. Simplifed Organizational Chart DepictingDoD Biodefense, Post-2004 (continued).


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MEDCOM, U.S. Army Medical Command;MIDRP, Military Infectious Diseases Research Program;MITS, Medical Identication and Treatment Systems;

SEC ARMY, Secretary of the Army;SECDEF, Secretary of Defense;USAMMDA, U.S. Army Medical Materiel Development Activity;USAMRIID, U.S. Army Medical Research Institute of InfectiousDiseases;USAMRMC, U.S. Army Medical Research and Materiel Command;USD(AT&L), Under Secretary of Defense for Acquisition, Technologyand Logistics;USD (P&R), Under Secretary of Defense for Personnel and Readiness;WRAIR, Walter Reed Army Institute of Infectious Diseases

Figure 3. Simplifed Organizational Chart DepictingDoD Biodefense, Post-2004 (concluded).

As a result of the 2004 reorganization, managementof the DoD medical biodefense program became

split among four primary organizations. The Armylaboratories (primarily the U.S. Army Medical ResearchInstitute of Infectious Diseases for biodefense products)were still the primary executors of the program, butwere divested of any programmatic decision authority.The management of the technical base and advanceddevelopment research was now divided betweenthe Defense Threat Reduction Agency (subordinateto the Under Secretary of Defense for Acquisition,Technology, and Logistics) and the Joint ProgramOfce (subordinate to the Army Acquisition Executive).The Joint Requirements Ofce (under the Chairman, Joint Chiefs of Staff, Force Structure, Resources, andAssessment Directorate) was now responsible forprogram requirements and planning, programming,

budget, and execution (PPBE) activities. Coordinationof product development across the divide betweenthese organizations does not appear to exist in any


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measurable degree, and there is little to no corporateagreement on product planning, or even product

requirements (to be addressed in more detail under theRequirements section). The Joint Requirements Ofce,Defense Threat Reduction Agency, and Joint ProgramOfce representatives initiated triad meetings withan objective of attempting to coordinate the program.However, at least from the perspective of the executinglaboratories, there has been little to no improvementand no tangible and clear guidance birthed fromthese periodic meetings. The result of this leadershipand management void is inefcient use of the DoDsbiodefense resources, including infrastructure andpersonnel. In the absence of a coordinated effortdirected from a corporate level (which appeared tobe the intent of the reorganization), the laboratoryresearchers are most apt to follow their own interests,

and an extremely competitive, rather than cooperative,research environment divides rather than unites theefforts.

Furthermore, the current structure and absence ofany coherent and coordinated corporate developmentplan creates an environment that allows, or evenencourages, political inuence and decisions basedon issues other than customer requirements, science,program plans, and risk analysis. Individuals withoutrequisite knowledge or experience in pharmaceuticalproduct development are placed in high-level,decisionmaking positions. When approached toconsider special funding set-asides, such individualsinability to review critically and discuss the scienticdata, coupled with a lack of a prospectively-dened

decisionmaking process, leaves them vulnerable tobeing inuenced by whoever can tell them a convincingstory. By occupying high level positions, they gain


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the authority to unilaterally decide to direct millionsof dollars to fund specic efforts. The programmatic

impact of such political inuence is to dilute programresources of funding and personnel that could orshould be devoted to higher priority efforts and alsoto set the conditions for unnecessary duplication ofapproaches and poorly coordinated efforts. Even if anew project has the potential to be a valuable additionto the overall program, the effort should not beconsidered in a vacuum, but rather be integrated fullyinto an overarching plan and assigned to the mostqualied (rather than the most politically connected)individual(s).

Finally, a noteworthy problem with the currentthe DoD biodefense program management, and instark contrast to the industry model, is that there is nobottom line about which one needs to worry. There

is no necessity to dene or meet any developmentalmilestones. Program funding continues year afteryear, regardless of program productivity in eldinguseable countermeasures for the warghter. Althoughthe 2004 DoD biodefense reorganization was intendedto improve coordination and oversight, the lack ofqualications and experience at the reviewer levelallowed programs that should have been terminatedto persist instead, based simply on promises of futureperformance, rather than scientic data and riskanalysis. In spite of all of the DoD-mandated programreviews and oversight, there is a dearth of thoseparticipating in the reviews who have the experienceand knowledge to critically assess the presentation,data, conclusions, or recommendations. There is,

therefore, a faade of accountability, but in fact thereis no accountability required, unlike industry with theneed to justify expenditures and investments with theshareholders.


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The diffuse program structure, lack of coherentand focused plans, and absence of qualied program

managers described above caused a lack of urgencyin tracking programs through to fruition, that is,availability of licensed products. This inevitably left theDoD unprepared when faced with crises of heightenedbiological warfare or terrorist threats, such as may bepresent in military conict and/or war. Historically,such times of national crisis stimulate sudden interest inpushing all available technologies out to the deployedsoldier, and there is a predictable call to assess allmedical products still in the developmental pathway,to determine if any exist that might be able to undergorapid elding. While this approach is effective withregard to weapons systems, vehicles, and body armor,for example,25 it is not a preferred solution for medicalproducts. Attempting to eld unlicensed medical

products for the purpose of force protection has beenfraught with difculty and controversy.26 Although theactual safety risk to service members receiving suchan unlicensed product would likely be low (becausesuch products generally would have an establishedsafety prole, with only unproven efcacy), there is amore signicant risk that recipients of such productswould falsely perceive that they have protectionthat may not exist. The greatest risk, however, is theDoDs credibility and reputation with the FDA andthe public. It is demonstrated repeatedly that whenthe DoD attempts to administer unlicensed productsin a deployed environment, it is unable to meet thestringent recordkeeping and protocol requirements ofthe FDA. Protocol violations then become the subject

of Government Accounting Ofce investigations,negative publicity, and public suspicion, all of whichunnecessarily blemish a well-intended program.


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Rather than exerting pressure to get new medicalsolutions in the eld at the time of national crisis, the

DoD program leaders would be better off to demand,from their research laboratories, a persistent urgencyto eld products and a focused management of theresearch effort to meet this end. Considering the longtimelines associated with product development andlicensure, even in the best and most efcient programs,biodefense research cannot afford the luxury of months,years, or decades of unfocused and poorly managedprograms.

Impact of the Organizational Structure.

Issues spanning the entire biodefense productdevelopment pathway reect shortcomings of thefragmented program structure described above

and depicted in Figure 3. The U.S. Army MedicalResearch Institute of Infectious Diseases is the DoDsprimary biodefense research laboratory, employingover 800 staff, with access to 40,500 net square feetof biosafety level (BSL)-3 and 6,700 net square feet ofBSL-4 biocontainment laboratory space, necessary forresearch on the worlds most dangerous pathogens.The U.S. Army Medical Research Institute of InfectiousDiseases scientists, many of whom are leaders in theirelds, have signicantly contributed to biodefense. Withregard to product successes, however, developmentaltimelines far exceed industry standards, and theabilityof the DoD to see product development through toproduct completion is diminished by opportunitiesfor efforts to become derailed primarily due to

ineffective coordination among ofces, disagreementon requirements and priorities, lack of prospectivelydened developmental milestones and decision points,or funding instability (Figure 4).27


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Product

DevelopmentTimeline

Status

Cu

rrentProgram

Ma

nager

Comments

Su

ccess

Vaccine1

Techbase:9years(1996-2004)

MSA:2004

MSB:

2005

Inadvanceddevelopment:One

oftwocompetingproducts

(theotherbeinganon-DoD

candidate)forupcoming

downselectdecision(2006)

JVAP

Labwasslow

toassume

vaccinemission;lost2years;now

in

jeopardyoflaggingbehin

dcompetitor

Un

knownat

thistime

Vaccine2


MSA:2000

Inadvanceddevelopment:

licensureplannedfor2012

JVAP

Couldhavebeenreadyfortransitionsoonerbutlabcontinued

basicresearchinlieuofvaccinefocus

Fu

tureDoD?

Vaccine3


MSA:None;JVAPdidnothavefunding

Productstalled.

Nodevelopment

plan

No

ne;JVAPplan

for

sequential

de

velopmenthad

tim

elineoutto

~2

018.

NIAID

fundedcontinuedresearchononeserotype,

but

unknownifthiswillcontin

ue

No

ne

Vaccine4

Techbase:4years(~1993-1997)

MSA:1998

NoPOMf

undingrecommended

(FY2008-2013).

JVAP(but

willchangeto

no

neifPOM

rec

ommendation

isapproved.)

InJune2006theJROun

expectedlyremovedfuturefunding

fromt

hisproduct(FY200

8-2013POMs

ubmission)and

terminatedasuccessfuladvanceddevelopmentprogram.

No

ne

Vaccine5

Techbase:18+years(1989-today)

MSA:None;JVAPdoesnothavefunding

NoPOMf

undingrecommended

(FY2008-2013).Readyto

transitionin2006,now

a2008

UFR

JS

TO

Techbasetimelinelength

enedbyfailuretokill1stand2nd

generationproductsearly.

USAMRIID

now

workingon3rd

generationvaccineeffort.

No

ne

Vaccine6

Techbase:~6years(1990-1996)

MSA:None

DroppedbytheDoD

(PI

deceased)

DH

HS(CDC)

JVAPassumedwhensto

odupofce(1996)butlater

transferredtoNIAID

NIAID

has

fun

dedtosmall

de

greeinthe

pa

st,butno

activeprogram.

Vaccine7

Techbase:16+years(1991-today)

MSA:1996,productdisapproved

Inactive.

NotfundedbyJSTO.

NoPOMf

undingforCMBS.

MRMC

legaltryingtolicense

tonon-DoD

pharmaceutical

company;CBMS/JSTOn

ow

unsureiftheywanttoretainit

instead?

No

ne

1996:CBMSMDAconcernedre:incapacitationversus

lethalityprotection

No

ne(possible

fut

ure

tec

hnology

tra

nsfer?)

Figure4.ProductOutcom

esfromtheU.S.ArmyMedicalResearc

hInstituteofInfectious

Diseases(USAM

RIID),DoDsBiode

fenseLeadLaboratory(continued).


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One such example is the current fate of a vaccineagainst Threat Agent 5 (Figure 4, row 5). The U.S.

Army Medical Research Institute of Infectious Diseaseshas received funding to research Threat Agent 5 inthe technology base for over 18 years. This researchculminated in FY06 in candidate Vaccine 5 withdemonstrated efcacy in a nonhuman primate model;a candidate that appears to be sufciently maturefor a transition to advanced development (ChemicalBiological Medical Systems Joint Project ManagementOfce). The Chemical Biological Medical Systems JointProject Management Ofce has been unsuccessful insecuring a funding wedge for this vaccine candidate inthe Program Objective Memorandum (POM) beginningin FY06. POM preparation is the responsibility of theJoint Requirements Ofce, an ofce which is completelydissociated from the product developmental efforts. The

Defense Threat Reduction Agency, now viewing thisvaccine as a mature candidate, appears to be unlikelyto continue to fund the effort beginning in FY07.28Candidate Vaccine 5, therefore, despite the millions ofdollars and years of manpower devoted to bringing itto the cusp of success, is perched precariously on theedge of transition from the Defense Threat ReductionAgency to Chemical Biological Medical Systems JointProject Management Ofce and is in serious danger ofdropping into the abyss between these organizations.The scientic base is left without important initialtesting in humans, a vital step in the developmentalpathway necessary to validate the medical approachand all of the preclinical research invested in the productup to that point. Most importantly, the warghter is

left without the chance of having a licensed product toprotect against this threat.

The development of a vaccine to protect againstThreat Agent 7 provides a second example (Figure


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4, row 7). The U.S. Army Medical Research Instituteof Infectious Diseases received funding to conduct

technology base research on protection against thisthreat for over 16 years. In 1996, the U.S. Army MedicalResearch Institute of Infectious Diseases presented itscandidate Vaccine 7 to the advanced developer fora milestone A transition decision (decision point tocontinue an acquisition program into the TechnologyDevelopment, or advanced development phase).The Milestone Decision Authority at that timedisapproved the transition, because of concerns aboutthe requirements for this product. There is no record,however, of concern over requirements from the ofceresponsible for requirements generation, at that time,the Army Medical Department Center and School (seeFigure 2).

Vaccine 4 provides yet a third recent example. Until

June 2006, this candidates developmental pathwayshowcased how the medical acquisition system shouldwork. After a mere 4 years of technology base research(1993-97), candidate Vaccine 4 smoothly transitioned tothe advanced developer (Chemical Biological MedicalSystems Joint Project Management Ofce) as a result ofa favorable milestone A acquisition decision. Althoughits continued development was somewhat resource-constrained, projected funding was sufcient to fullla plan for obtaining product licensure in 2014. Acompletely unanticipated turn in the program occurredin June 2006, however, when the Joint RequirementsOfce recommended removing all Vaccine 4 fundingfrom its FY 2008-13 POM submission. Although the FY2008-13 POM recommendations are not yet nalized,

at this late stage in the process the prediction is thatthe Joint Requirements Ofces decision will stand.Without warning, the DoDs Vaccine 4 development


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program was thereby effectively terminated, based onunknown criteria of which a scientic review of the

product does not appear to have been a part.The consistent themes that resonate throughout the

product failures such as these are poor requirementsdocumentation, a lack of an overarching plan, andineffective coordination between organizations. Theseweaknesses often result in potential products gettingdelayed or dropped mid-development and in managerswho are unable to negotiate the transitions, or producthand-offs.

Requirements.

Another challenge of the DoD pharmaceuticalacquisition system is a clear articulation of requirements.The Joint Requirements Ofce for Chemical, Biological,

Radiological, and Nuclear Defense has the responsibilityof identifying gaps and proposing solutions that itdenes as requirements (or required capabilities) in oneof four Joint Capabilities Integration and DevelopmentSystem documents. The document that guides researchin the technology base (pre-Milestone A) is the broadlywritten Initial Capabilities Document, which shouldpropose a prioritized list of non-materiel and materielapproaches to provide the desired joint warghtingcapability.29 In fact, a Joint Requirements Ofceinformation brief illustrates the approval processfor program priorities (Figure 5),30 but interestingly,this process appears to involve only the combatantcommanders, Joint Requirements Ofce, and JointRequirements Oversight Council; there is no indication

of prioritization subsequently being passed down tothe Joint Program Ofce and Science and Technologyprogram ofces that should be managing the research


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programs. One could presume that these prioritieswould be delineated in the Joint Requirements Ofces

requirements documents, but unfortunately, the InitialCapabilities Documents applicable to biodefensepharmaceutical research, dening warghter needs forprophylaxes31 and therapeutics,32 to prevent and treatdisease, respectively, neither specify nor prioritizedisease-causing agents of interest.

JROCSECArmy

JRO JPEO

S&T

OSD Comptroller

ATSD(NCB)

Approved Priorities

Proposed Priorities

Input for Priorities

Approved ORDs

Input for ORDs

Approved CACT I ORDs

Draft CACT I ORDs

Draft Budget

POM Submissi on

Draft POM

Build POM

Services

Combatant Commanders

Component Commanders

ACAT, Acquisition Category;ATSD(NCB), Assistant to the Secretary of Defense for Nuclear,Chemical and Biological Defense Programs;

JPEO, Joint Program Executive Ofce;JRO, Joint Requirements Ofce;JROC, Joint Requirements Oversight Council;ORD, Operational Requirements Document (now replaced byCapability Development Documents, CDDs);OSD, Ofce of the Secretary Defense;POM, Program Objective Memorandum;S&T, Science and Technology.

Figure 5. JROC-Approved JRO-CBRNDefense Process.


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In the transition from a biodefense researchprogram based on a prioritized, validated threat list, to

capabilities-based requirements,33

the program gainedexibility but lost focus. Specication of priorities isvital to making wise programming and budgetingdecisions. The current void of research prioritiesresults in funds being spread broadly across a largenumber of research areas, rather than being centeredon a few areas ranked as most important. Lack of focusequates to slow progress, even, at times approximatingBrownian motion.

THE CHANGING NATIONAL LANDSCAPEFOR BIODEFENSE

Funding.

Before 2001, there was not a large federal investmentin biological defense research and development andthe funds that were devoted to that mission primarilyresided within the DoD. This reected the ColdWar-era perception that the only signicant risk ofbiological attack was to deployed warghters andnot to the U.S. civilian population. The DoD was thelead agency in biological defense, and the U.S. ArmyMedical Research Institute of Infectious Diseaseswas its primary executing laboratory. The annualDoD budget for biological defense research averagedapproximately $60M from FY99 to FY01.34

After the events of 9/11 and the post-9/11 anthraxletters, the U.S. populace recognized its vulnerabilityto biological terrorism, and the governmental response

was to direct a signicantly increased investmenttoward protection against purported biologicalthreats.35 Those within the DoDs biological defense


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research and development circle predicted that theArmy would be designated as recipient and manager

of these funds. Shockwaves echoed through the DoDsbiodefense community when it found instead thatthe National Institutes of Health (NIH) under theDepartment of Health and Human Services (DHHS)would be the recipient of the majority of this budgetincrease and assume the role as the lead federal agencyfor developing biodefense countermeasures.36

This was indeed an interesting twist of fate. Before2001, in spite of the criticism of the effectiveness ofthe DoDs medical biodefense management, the DoDwas still the only federal department with measurableexperience or success in medical product development.Development of products was a completely newmission for the NIH, whose laurels rested on its abilityto conduct basic research and contribute immensely

to the academic body of literature and generalknowledge base. One could speculate on the basis forthis decision and whether or not the DoDs inability toreform its structure and management of the programas repeatedly recommended by expert panels andthe Government Accounting Ofce37 perhaps taintedcondence in the DoD to manage an even largerprogram. Another possibility reects the perceptionthat there is a major difference in the countermeasuresneeded for the militarys protection versus that of thecivilian population. Because the NIH mission centerson public health, the funds provided for research todevelop countermeasures to protect U.S. citizenslogically could be seen as falling within the NIHdomain, rather than that of the DoD.

As illustrated in Figure 6,38 where the DoD assumeda modest post-9/11 increase in annual biodefensefunding of approximately $30M, the DHHS annual


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budget increased over $1500M. The DoD was suddenlyneither the sole player nor even the major player in

this research domain. The NIH responded to its newmission quickly, producing the NIAID Strategic Planfor Biodefense Research in February 2002.39

All Other

Natl. Science Foundation

NASA

Health & Human Services

EPA

Homeland Security

Defense

Agriculture

5,000

4,000

3,000

2,000

1,000

0

1998 1999 2000 2001 2002 2003 2004 2005 2006

Federal Homeland Securi ty R&D*, by Agency(budget authority in millions of constant FY 2005 dollars, FY 1998-2006)

Source: AAAS, based on Office of Management and Budget data.

Includes conduct of R&D and R&D facilities.* 1998-2001 data are

for R&D within funding to combat terrorism.

MARCH 05 REVISED 2005 AAAS AAAS

Figure 6. Federal Homeland Security Research andDevelopment Funding, by Agency (in $M).

Various ofces and individuals within the DoDbiodefense research program acted quickly to positionthemselves to be able to leverage DoD knowledge andresearch and development resources to compete forNIAID funding. Any coordination that did take placehowever, was generally at an individual level. Therewas no overarching plan to integrate DoD and NIAID

biodefense efforts. To the contrary, NIH grants policiesactually presented obstacles to DoD scientists. The NIHpolicy prohibits federal institutions from receiving


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grant funds for Facilities and Administrative expensesand salaries for permanent federal employees.40 It is

therefore impossible for a DoD scientist to conductresearch using the NIH grant mechanism unless thatindividual is able to justify that same research need toa second, discrete customer who is willing to cost shareand provide the salary and laboratory overhead fundsto support that work.

The DoD, primarily at the U.S. Army MedicalResearch Institute of Infectious Diseases, has uniqueand critical infrastructure, biocontainment capabilities,and intellectual capacity in biowarfare and bioterroristthreat agents at a concentration unequalled anywhereelse in the world. The DoD does not, however, receivea budget equivalent to the scope of its mission anddoes not have the structure and processes in place tomanage its limited funds efciently.

Biodefense Participants.

The infusion of over $1.5B per year into medicalbiodefense countermeasure research has resulted inan exponential increase in the scientic investigatorsand institutions interested in taking on a biodefensemission. Fund it, and they will come. In the pre-9/11era, the DoD had a corner on this market, but since2002 the NIH has been able to stimulate tremendousnational interest in biodefense research both withinacademia, through competitive grant awards for basic(early) research, and also in industry, through contractawards, generally for advanced research on moremature candidate products. Yet another new funding

mechanism, Project Bioshield (with an available$5.6B over 10 years for procurement of biodefensecountermeasures for the national stockpile41), has drawn


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danger of losing prominence and the ability to makesubstantial contributions.

RECOMMENDATIONS

Recommended Action.

The U.S. military and the nation require medicalcountermeasures to prevent and treat disease thatwould result from the intentional use of biologicalagents. Pharmaceutical development, even in the bestand most efcient circumstances, is a long and complexprocess. The DoD, despite its unique infrastructure,intellectual repower, and decades of experience,has many obstacles blocking its road to success, suchas a diffuse organizational structure, lack of a singleprogram leader, managers without the necessary

qualications and experience, and the absence ofany overarching plans. Despite numerous programreviews and specic recommendations for programimprovement, the DoD has been either unwilling orunable to improve the program structure to position itfor success.

The NIAID, under the NIH, recently has receiveda large budgetary increase to support a new publichealth biodefense mission. There are more similaritiesthan differences between the NIH and the DoDmissions, and there is no clear justication as to whythese programs must remain distinct. The NIAID has adistinguished history in funding basic research, but hasno history or experience in product development. Evenwithin the NIAID, although the biodefense strategic

plan calls for development and licensure of products,it has neither prioritized this mission nor modied itsorganization sufciently to reect the best [industry]business practices required to achieve this goal.


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It is in the best interest of both warghter protectionand homeland defense to consolidate all national

biodefense research and development resources undera single organization. This organization would be ofsufcient size, complexity, and mission priority thatit should be granted agency status under DHHS42 asthe National Biological Countermeasure DevelopmentAgency (NBCDA) (see Figure 7). All biodefenseresources of both the DoD (e.g., Defense ThreatReduction Agency and DARPA chemical and biologicaldefense research programs involving pharmaceuticaldevelopment; the Chemical Biological Medical Systems Joint Project Management Ofce; the U.S. ArmyMedical Research and Materiel Commands MedicalResearch Institute for Infectious Disease, and resourcesof its Walter Reed Army Institute of Research involvingchemical and biological defense pharmaceutical

development; see Figure 3) and relevant ofces andbranches of DHHS (e.g., the NIH, DHHS, and itsOfce of Research and Development Coordination,and Centers for Disease Control), including budgets,personnel, and infrastructure should be assigned tothe NBCDA. In so doing, the reassigned individualsand facilities must lose their previous organizationsidentities and become completely unied (not simplyco-located) and focused, from the agencys inception,on a singular mission.


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Organizational structure depicting placement of the proposedNBCDA.

CDC, Centers for Disease Control and Prevention;DHHS, Department of Health and Human Services;FDA, Food and Drug Administration;NBCDA, [proposed new] National Biological CountermeasureDevelopment Agency;NIH, National Institutes of Health.

Figure 7. Proposed New Agency for NationalBiological Countermeasure Development.

In establishing this new agency, it is essential torecognize the lessons learned from the DoD, NIH,and the pharmaceutical industry. The new agency

must adopt a structure and management that will bestreamlined, exible, and efcient, with delineation ofmanagement and resources devoted to discovery work(best patterned after the NIH model) and productdevelopment (best patterned after the industrymodel).

Risks and Risk Mitigation.

Reorganization that does not reect an improvementin the ability to accomplish the mission is detrimental


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to programs. If the NBCDA is not created withprospective thought and planning, the end result could

be even further degradation of productivity.The NBCDA must have a clear mission statement

articulated even before the rst individual is assigned.The mission of this organization is to develop biologicalcountermeasures. Ultimate success is measured onlythrough elding of these products. With all assignedpersonnel understanding the vision and mission upfront, their energies can better be immediately devotedtoward teaming cooperatively to discover solutions.

The NBCDA must be created with a clearorganizational structure, containing minimal layers inits hierarchy, with a single responsible individual atthe top who is accountable for the entire program.

It is vital that key positions be lled with individualsfully qualied and experienced in both the science and

business of pharmaceutical product development.That individuals who are either politically, rather thanscientically, qualied, or merely available, could beplaced in leadership and management positions is ahigh risk.

A risk-mitigation strategy to ensure clarity ofvision, organizational structure, and the hiring ofsufciently qualied staff would be for the governmentto constitute and seek the advice of an external reviewcommittee, comprised of experts in pharmaceuticalproduct research and development, drawn from bothindustry and academia,43 during the development ofthe NBCDA. Guidance provided by this body wouldbe invaluable both during the formative stages of theagency and throughout its future operation.

A risk related to hiring the most qualied individualsis the inability of the federal government to offersalaries, benets, and incentives that are competitive


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with industry. At this time, the relative inexibility ofhiring options within this system makes this risk one

that the government cannot easily mitigate and wouldhave to accept.

Another potential risk of transferring all biologicaldefense research and development out of the DoD isthat the mission of the NBCDA might not cover allaspects of the current DoD program adequately, norspecically address military requirements. In thepast, there was a signicant difference in the militaryapproach to biowarfare protection and the civilianapproach to protection against bioterrorism. Themilitary favored development of vaccines to limitmorbidity on the battleeld and maintain a functionalwarghting force. Vaccines were seen as a solutionwhich could be applied to the entire military population,being a relatively small force. Recent experience with

anthrax and smallpox vaccines and fallout relatedto Gulf War illnesses, however, demonstrate thatthe vaccine policy regarding the total military forceis difcult to apply. The civilian approach favorstherapeutics, administered on a limited basis only tothose known to be exposed to an agent. As the militaryhas begun to recognize the impracticality of massvaccinations and limitations regarding specicity ofvaccines to a single agent versus potentially broaderactivity of therapeutics, the military is shifting awayfrom vaccines and embracing therapeutics. Thereforethis past divergence of missions already is narrowing.Currently, the DoD requirements44 appear to be almostidentical to those delineated in the NIAID StrategicPlan.45

Two other areas in which the DoD biodefenseprogram contributes, are providing biodefense trainingand conducting disease outbreak investigations.


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Both training and global outbreak response clearlyfall within the Centers for Disease Control mission,46

however, so the militarys involvement in thesedomains might be viewed as duplicative. As long asthe biodefense elements of the Centers for DiseaseControl are subsumed into the NBCDA, these missionswould continue without need for dedicated DoDinvolvement.

It is important to ensure availability of assignmentswithin the NBCDA for both military biomedicalscientists and clinicians, so the military would not loseits expertise, which is necessary to maintain to supportmilitary deployments. Interagency agreement betweenthe DoD and NBCDA should permit cross-assignmentof personnel to maintain military skills and benetfrom continued DoD contributions to the nationalmedical biodefense effort.

CONCLUSION

The DoD has tremendous and unique resourcesand skills that could contribute immensely towarddeveloping critically needed countermeasures againstbiological weapons. Poor DoD program organizationand management, however, have resulted in adysfunctional program with little success in measurableoutcome. While DHHS has a signicantly increasedbudget for a biodefense mission closely duplicative tothat of the DoD and, while the NIH (within DHHS)has a stellar reputation with regard to basic academicresearch, DHHS is inexperienced and unproven in itsability to develop products. Pharmaceutical product

development is a long, complex process and requiresspecial organizational structure, highly qualiedleadership and management, and long-term and


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stable resourcing, including funding. The UnitedStates would benet greatly by the consolidation of all

federal biodefense resources into a new agency underthe DHHS, specically designed to meet the stringentdemands of product development.

ENDNOTES

1. Henry A. Kissinger, National Security Decision Memorandum(NSDM) 35, United States Policy on Chemical Warfare Program

and Bacteriological/Biological Research Program, Washington, DC,November 25, 1969, p. 3.

2. Mark Dertzbaugh, U.S. Army Medical Research Institute ofInfectious Diseases, Chief, Business, Plans and Programs Division,telephone interview by author, April 10, 2006.

3. Code of Federal Regulations, Title 21, Parts 50, 56, 312,Subpart I of Part 314, Subpart G of Part 601, New Drug and BiologicalDrug Products; Evidence Needed to Demonstrate Effectiveness of New

Drugs When Human Efcacy Studies Are Not Ethical or Feasible,Washington, DC, 2002.

4. Mark E. Gebicke, Testimony before the Committee onVeterans Affairs, U.S. Senate, Chemical and Biological Defense:Observations on DODs Plans to Protect U.S. Forces, Washington,DC: U.S. General Accounting Ofce, March 17, 1998, p. 9.

5. Department of Defense, Use of Investigational New Drugs forForce Health Protection, DoD Directive Number 6200.2, Washington,DC: August 1, 2000, pp. 3-11.

6. Pharmaceutical Research and Manufacturers of America,Pharmaceutical Industry Prole 2005. Washington, DC: PhRMA,March 2005: pp. 4-5.

7. Joseph A. DiMasi, Ronald W. Hansen, and Henry G.Grabowski, The Price of Innovation: New Estimates of DrugDevelopment Costs,Journal of Health Economics, Vol. 22, 2003, p.180.

8. Pharmaceutical Research and Manufacturers, PharmaceuticalIndustry Prole 2005, pp. 4-5.

9. Joseph A. DiMasi, Risks in New Drug Development:Approval Success Rates for Investigational Drugs, ClinicalPharmacology & Therapeutics, Vol. 69, No. 5, 2001, p. 305.


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10. Report to the Deputy Secretary of Defense by theIndependent Panel of Experts, Department of Defense Acquisition ofVaccine Production, AVP, Vol I, December 2000, p. 12.

11. Ibid., pp. 3-4.

12. Ibid., pp. 32-35.

13. Lois M. Joellenbeck, Jane S. Durch, and Leslie Z. Benet,eds., Committee on Accelerating the Research, Development,and Acquisition of Medical Countermeasures Against BiologicalWarfare Agents, National Research Council, Giving Full Measureto Countermeasures: Addressing Problems in the DoD Program toDevelop Medical Countermeasures Against Biological Warfare Agents,Washington, DC: The National Academies Press, 2004, pp. 4, 44.

14. Report by the Independent Panel of Experts, DoD Acquisitionof Vaccine Production, AVP, p. 10.

15. Wikipedia, Sloth; available from http://en.wikipedia.org/wiki/Sloth, accessed April 13, 2006.


17. Ofce of Management and Budget, Unclassied RDT&EBudget Item Justication Sheet, R-2 Exhibit, Appropriation/BudgetActivity RDT&E, Defense-wide BA2 Applied Research R-1, ItemNomenclature Biological Warfare Defense PE 0602383E, February2002; Ofce of Management and Budget, Unclassied RDT&EBudget Item Justication Sheet, R-2 Exhibit, Appropriation/Budget Activity RDT&E, Defense-wide BA2 Applied Research R-1, Item Nomenclature Biological Warfare Defense PE 0602383E,February 2004, pp. 107-110.

18. Lieutenant Colonel Harry F. Slife, Jr., Medical BiologicalDefense Research Program, brieng slides for the Armed ForcesEpidemiological Board 2004 Spring Meeting, May 11-12, 2004, p.13.

19. DARPA Transition Program, electronic message toColonel Coleen K. Martinez, June 1, 2006.

20. Under Secretary of Defense E. C. Aldridge, Jr., AcquisitionDecision Memorandum--Management of the Chemical/Biological

Defense Program, memorandum for Secretary of the Army,Washington, DC, September 19, 2002.



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22. Stanley M. Lemon, et al., eds., Protecting Our Forces:Improving Vaccine Acquisition and Availability in the U.S. Military,Washington, DC: Institute of Medicine of the National Academies,2002, pp. 55-76.

23. Ibid., p. 12.

24. Lois M. Joellenbeck, Giving Full Measure to Countermeasures,p. 46.

25. Lieutenant General Joseph L. Yakovac, Jr., Testimony beforethe House Armed Services Committee, U.S. Senate, Regarding theArmys Force Protection Acquisition Process, 108th Cong., 2d sess.,April 21, 2004, p. 2.

26. DoD, Investigational New Drugs for Force Health Protection,p. 9.

27. Mark Dertzbaugh, telephone interview by author; NIAIDRole in Biodefense Research, interview by author, April 21, 2006.

28. Results of POM Meeting, electronic message to ColonelColeen K. Martinez, April 5, 2006.

29. Defense Acquisition University, Introduction to Defense

Acquisition Management, 7th Ed., Fort Belvoir, VA: DefenseAcquisition University Press, 2005, p. 39.

30. Don W. Bailey, Joint Requirements Ofce for Chemical,Biological, Radiological, and Nuclear Defense Information Brief,Brieng Slides, Washington, DC, January 14, 2003, p. 5.

31. Director Joint Requirements Ofce for Chemical, Biological,Radiological, and Nuclear (JRO-CBRN) Defense, Initial CapabilitiesDocument (ICD) for Joint Medical Biological Warfare Agent Prophylaxes,

Washington, DC, September 14, 2004, pp. 9-10.32. Director Joint Requirements Ofce for Chemical, Biological,

Radiological, and Nuclear (JRO-CBRN) Defense, Initial CapabilitiesDocument (ICD) for Chemical, Biological, Radiological, and NuclearCBRN) Therapeutic Pharmaceuticals, Washington, DC, July 18, 2005,pp. 10-11.

33. Congress, Senate, Committee on Health, Education, Laborand Pensions Bioterrorism and Public Health Preparedness

Subcommittee, Testimony of Colonel Joseph Palma, M.D., USAF, Medical Director, Ofce of the Deputy Assistant to the Secretary ofDefense for Chemical and Biological Defense: Hearing on MedicalCountermeasures, June 9, 2005, pp. 2-3.


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34. Mark T. Dertzbaugh, Maintaining USAMRIID Leadershipin Biodefense--Stakeholder Brief on USAMRIIDs ProposedStrategic Vision, draft brieng slides, Fort Detrick, MD, March31, 2006, p. 21.

35. Milton Leitenberg, Assessing the Biological Weapons andBioterrorism Threat, Carlisle Barracks, PA: Strategic StudiesInstitute, U.S. Army War College, December 2005, pp. 65-66.

36. George W. Bush, Homeland Security Presidential Directive 10:Biodefense for the 21st Century, Washington, DC: The White House,April 28, 2004.

37. Lemon, Protecting Our Forces, pp. 57-69; Report by theIndependent Panel of Experts, Acquisition of Vaccine Production,27-31; General Accounting Ofce, Chemical and Biological Defense:Observations on DODs Risk Assessment of Defense Capabilities,Washington, DC: U.S. General Accounting Ofce, October2002, pp. 12-15; Lynne Gilllan, et al., Taking the Measure ofCountermeasures: Leaders Views on the Nations Capacityto Develop Biodefense Countermeasures, Biosecurity andBioterrorism: Biodefense Strategy, Practice, and Science, Vol. 2,No. 4, 2004, pp. 323-324; Joellenbeck,

Giving Full Measure toCountermeasures, pp. 4-15.

38. Kei Koizumi, Federal Government Funding of R&Dand the Federal Budget Process, brieng slides, OPM Science,Technology, and Public Policy Seminar, December 2, 2005, p. 19.

39. U.S. Department of Health and Human Services, NationalInstitutes of Health, NIAID Strategic Plan for Biodefense Research,Bethesda, MD, February 2002, pp. 1-12.

40. National Institutes of Health Ofce of Extramural Research,Grants Policy Statement, Part II: Terms and Conditions of NIHGrant Awards, Subpart B: Terms and Conditions for SpecicTypes of Grants, Grantees, and Activities, December 2003.

41. Sandra Basu, Lawmakers Study Incentives for Bioshield,July 2005; available from www.usmedicine.com/article.cfm?articleID=1118&issueID=76, accessed March 13, 2006.

42. NIAID Role in Biodefense Research, interview by author,April 21, 2006.

43. Joellenbeck, Giving Full Measure to Countermeasures, p. 61.

44. Joint Requirements Ofce ICD for Biological Warfare AgentProphylaxes, Washington, DC, September 14, 2004, pp. 3-8; Joint


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Requirements Ofce, ICD for CBRN Therapeutic Pharmaceuticals,pp. 3-12.

45. U.S. DHHS, NIAID Strategic Plan for Biodefense Research, pp.1-12.

46. Centers for Disease Control and Prevention, Vision,Mission, Core Values, and Pledge, available from www.cdc.gov/about/mission.htm, accessed April 25, 2006.

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