July 2001

Report on Biological Warfare Defense

Vaccine Research & Development

Programs
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0101042.doc i

Executive Summary

Section 218 of the Floyd D. Spence National Defense Authorization Act for

Fiscal Year 2001, Public Law (PL) 106-398 (at Appendix A) requires the submission

of a report to the congressional defense committees on the acquisition of biological

defense vaccines for the Department of Defense (DoD). As required by section 218,

PL 106-398, this report addresses: 1) the implications of relying on the commercial

sector to meet the DoD’s biological defense vaccine requirements; 2) a design for a

government-owned, contractor-operated (GOCO) vaccine production facility; 3)

preliminary cost estimates and schedule for the facility; 4) consultation with the

Surgeon General on the utility of such a facility for the production of vaccines for the

civilian sector and the impact of civilian production on meeting Armed Forces needs

and facility operating costs; and 5) the impact of international vaccine requirements

and the production of vaccines to meet those requirements on meeting Armed Forces

needs and facility operating costs.

Since 1998, senior leadership has amplified the focus on resolution of

difficulties in securing a ready and reliable access to safe and effective vaccines for

use against biological warfare agents. As part of the DoD’s vaccine initiative, DoD

contracted with Science Applications International Corporation (SAIC) to select an

independent panel of experts to assess the DoD acquisition of vaccine production

programs and report their recommendations for improvement to the Deputy Secretary

of Defense. The panel prepared a report to reflect its independent opinions for

consideration by DoD. This report (at Appendix B) discusses vaccine industry

constraints and concludes that the size and scope of the DoD program is too large for

either DoD or industry alone. It recommends the application of a combined,

integrated approach by DoD and industry, coupled with better alignment with industry

best practices. The Department is studying the Panel’s recommendations.

Substantial advancement has been accomplished in defining the scope and

operating concepts for a DoD GOCO vaccine production capability. A preliminary

25-year life cycle cost estimate for such a facility would be approximately $1.56

billion. This estimate includes approximately $386 million for designing, building

and validating the facility, $915 million for operations and $259 million for other

government costs. The facility would accommodate three bulk vaccine production

suites and modular design would allow for expansion. A preliminary projected

schedule would allow for production to begin approximately seven years after project

start, with the current anthrax vaccine having highest priority. Moreover, the

Department consulted with the U.S. Surgeon General about the development of a

GOCO vaccine production facility and in his letter (at Appendix C), he encourages

DoD to proceed with its plans.

The actions above have significantly aided in analyzing the issues associated

with securing vaccines to protect our forces.
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0101042.doc 1

Introduction

Over the past decade, since the Gulf War, it has become most evident that the

Department of Defense (DoD) must secure ready and reliable access to safe and

effective vaccines for protection against biological warfare agents. Vaccines,

coupled with effective immunization policy for safeguarding the force from

biological warfare agents, are the most effective technological method for

enabling successful force projection to any global region where vital interests of

the United States are contested.

Since 1998, senior leadership from the Department of the Army—the DoD

executive agency for biological warfare defense—and from the Office of the

Secretary of Defense has amplified our focus on resolution of difficulties in

securing a ready and reliable access to safe and effective vaccines for biological

warfare defense. It is a policy imperative that vaccines—regardless of their source

of manufacture—that are intended for force health protection are licensed by the

Food and Drug Administration (FDA). The current DoD vaccine acquisition

strategy focuses on the development of eight vaccines: Anthrax Vaccine Adsorbed

(AVA), Smallpox, Plague, Tularemia, Multivalent Botulinum, Next Generation

Anthrax, Ricin, and Multivalent Equine Encephalitis.

As a part of the DoD’s vaccine initiative, DoD contracted Science Applications

International Corporation (SAIC) to select an independent panel of experts to

assess the DoD acquisition of vaccine production programs and report its

recommendations for improvement to the Deputy Secretary of Defense.

Additionally, substantial advancement within the DoD and across federal, nonDoD agencies has been accomplished in defining the scope and operating concepts

for a DoD government-owned, contractor-operated (GOCO) vaccine production

capability. These actions together have significantly aided in analyzing the issues

associated with securing vaccines to protect our forces.

The following report is organized according to the report content requirements

prescribed by section 218 of Public Law 106-398 (Appendix A), which are in bold

type.

1. The Secretary’s evaluation of the implications of reliance on the

commercial sector to meet the requirements of the Department of Defense

for biological warfare defense vaccines.

In the congressional hearings on the Department of Defense’s Anthrax Vaccine

Immunization Program before the Senate Armed Services Committee on July 12,

2000, and before the House Armed Services Committee on July 13, 2000, the
0101042.doc 2

former Deputy Secretary of Defense, Mr. Rudy de Leon, testified that he asked the

Acting Assistant Secretary of Defense for Health Affairs and the Director of

Defense Research and Engineering (DDR&E) to contract with a private

organization to provide an independent review of the Department’s management of

vaccine procurement. The purpose was to provide for an independent third party to

give the Department both advice and to further ensure that our efforts are credible,

consistent and effective with the use of public monies in this area.

The DDR&E funded this study and assigned the study support task to SAIC

using an existing contract delivery order. A panel of experts, with expertise in the

scientific, regulatory and industrial aspects of vaccine production, and Federal

procurement, was assembled by the contractor, SAIC, to conduct the study. SAIC

solicited nominees from industry and the government for potential panel members

and contacted them about their willingness and availability to participate in the

vaccine study effort. SAIC’s recommendations of potential panel members were

reviewed and accepted by DoD. The Panel Chair was fully responsible for and

directed the Panel’s effort. DoD and the SAIC staff provided support and assistance

as requested by the Panel Chair.

On November 29, 2000, the panel of experts presented their findings to the

then Deputy Secretary of Defense, that the scope and complexity of the DoD

biological warfare defense vaccine requirements were too great for either the DoD

or the pharmaceutical industry to accomplish alone. To put in perspective, within

the United States, vaccines are currently licensed to protect against approximately

20 diseases, whereas the DoD biological warfare defense program alone requires

vaccines to protect against almost an equal number of disease-causing, biological

warfare agents. In addressing this requirement, the Panel agreed with the DoD

vaccine acquisition strategy, which focuses initially on a limited set of

approximately eight vaccines. The Panel recommended that a combined

integrated approach whereupon DoD would work closely with the vaccine

industry and national scientific base, both private and public, to develop and

produce the vaccines that DoD needs would be a more effective acquisition

strategy. The Panel reported that this approach must draw upon the acquisition

management expertise of the DoD, incorporate the best practices of the

pharmaceutical industry, and draw on national scientific and technical strengths.

At an eight-vaccine scale, the Panel estimated that the DoD acquisition of

vaccine production program would require between $2.4 and $3.2 billion in

research and development costs over a 7- to 12-year period. The Panel also agreed

with the DoD plan to consider construction of a dedicated GOCO production

facility with an initial production capacity of three to four products, pilot

production and scale-up capacity. Resources for a GOCO were roughly estimated

by the Panel at $370 million in initial construction. This estimate is very much in
0101042.doc 3

line with the DoD’s estimate of $386 million in military construction (MILCON)

for a GOCO vaccine production facility.

The independent panel felt strongly about the benefits of long-term government

commitment, increased resources, innovative DoD business and program

management practices, and effective participation by established pharmaceutical

industry leaders in vaccine discovery, licensure, and manufacturing. However, it

must be recognized that many of the Panel’s recommendations are at variance with

Departmental policy, the existing vaccine acquisition strategy, as well as acquisition

and procurement practices. The report1 prepared by the independent panel is

provided at Appendix B. The Department is studying the Panel’s recommendations.

2. A design for a government-owned, contractor-operated facility for the

production of biological warfare defense vaccines that meets the

requirements of the Department for such vaccines, and the assumptions

on which that design is based.

A 35 percent design for a GOCO vaccine production facility (VPF) was

completed for the DoD in 1993. Shortly thereafter, the DoD vaccine acquisition

strategy was changed to a prime systems contractor, rather than a GOCO,

approach. This was done in anticipation that established private sector

pharmaceutical manufacturers would support DoD vaccine production

requirements. This strategy has not worked as well as expected. The 35 percent

design prepared in 1993 was used as the basis for a November 2000 concept study

and estimate prepared by Bio-Pharm Technologies, a division of Day and

Zimmerman, International, Inc. (DZII). The purpose of the latter study was to

develop a new conceptual cost estimate and schedule for design, construction, fitup, and qualification to FDA regulatory requirements for vaccine development,

licensure, and manufacturing as promulgated in Title 21 Code of Federal

Regulations (21CFR), Food and Drugs.

Major planning assumptions used for the November 2000 conceptual study and

estimate for the DoD GOCO VPF included the following.

• Large, well-established, pharmaceutical industry (i.e., vaccine)

manufacturers are unlikely to reverse their decades-long trend of relatively

inconsequential support of DoD vaccine production requirements.

• DoD must develop and acquire a second, licensed manufacturing source for

anthrax vaccine adsorbed (AVA) and other high priority vaccines for force

protection.

 

1

 Volume I summarizes the discussions and findings of the independent panel. Volume II contains copies

of briefings and documents provided to the Panel, and was not prepared or approved by the panel.

Therefore, it is not being forwarded.
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• DoD critical needs and reliance on vaccines for force protection, coupled

with the two previous assumptions, dictate that the DoD be the federal lead

agency for the GOCO VPF.

• The GOCO facility must contain flexible and expandable manufacturing

capacity for licensed production of eight DoD-critical vaccines, including

AVA, which is licensed to BioPort Corporation, Lansing, Michigan.

• Licensed vaccine production should begin in fiscal year (FY) 2008 with

early emphasis on AVA manufacturing.

• The DoD GOCO must contain three bulk production suites, one for each of

the following processes:

− spore-forming bacteria (i.e., AVA)

− microbial fermentation

− tissue culture (viral vaccines)

• GOCO manufacturing capabilities must be sufficiently flexible to support

expansion that is sufficient to accommodate high priority needs for

protection of civilian populations, both foreign and domestic, and to

effectively respond to changing biological weapons threats.

• On-site capabilities for animal testing are necessary.

• On-site quality control laboratories are necessary.

• Support spaces (administrative offices, warehouse, and utilities) must be

sufficient for an eight product scale and expandable to accommodate

potential contingencies.

Table 1 shows the vaccine production assumptions of the first eight DoDcritical products. An architectural drawing showing the relative space utilization

for the different functions is shown in Figure 1. Alternative designs will be

solicited and evaluated as one of the bases for selecting the contract operator(s) for

the facility.

Table 1. Vaccine Production Assumptions

Product Name Production Process

Anthrax Vaccine, Adsorbed (AVA) Bacterial spore-forming

Smallpox Vaccine Cell culture

Plague Vaccine Recombinant fermentation

Tularemia Vaccine Fermentation

Multivalent Botulinum Vaccine Recombinant fermentation

Next Generation Anthrax Vaccine Recombinant fermentation

Ricin Vaccine Recombinant fermentation

Multivalent Equine Encephalitis

Vaccine

Cell culture
0101042.doc 5

Figure 1. Architectural Drawing of DoD GOCO Vaccine Production Facility

3. A preliminary cost estimate of, and schedule for, establishing and bringing

into operation such a facility, and the estimated annual cost of operating

such a facility thereafter.

Using data provided in the concept study and estimate prepared by DZII,

Science Applications International Corporation (SAIC) prepared a life cycle cost

estimate (LCCE) for the design, construction, FDA qualification, and operation

through FY 2026 of a DoD GOCO VPF. SAIC applied the following ground

rules, assumptions, and major constraints to develop the LCCE.
0101042.doc 6

• Ground Rules:

− Cost estimates are developed in base year 2000 dollars (BY00$)

− January 2000, Office of the Secretary of Defense (OSD) Inflation

Indices were used.

− The DoD GOCO VPF life cycle is 25 years starting in FY02.

− Licensed production will start not later than FY08 and priority will

be given to AVA production.

− No surge capacity is planned for the GOCO VPF. However,

maximum production rates are planned for each suite. This equates

to a “dedicated suite” concept for vaccines that are planned.

− No contingency requirements are planned in the LCCE.

− Only DoD biological defense vaccines will be produced in the 25-

year life cycle for the GOCO VPF.

• Assumptions:

− National Environmental Policy Act (NEPA) compliance will require

2 years. However, design can be initiated after the first year’s

NEPA activity.

− Site selection will require approximately 6 months and may start in

FY01. The LCCE assumed a generic site.

− Vaccines will be stored in vials at the GOCO VPF—no bulk

storage—until released for use.

− Product yields are based on technical estimates and likely to change.

− AVA capacity during the first year of operation is 50 percent.

− Product shelf life was assumed to be 3 years for AVA and 2 years

for all other vaccines.

− The Joint Vaccine Acquisition Program biological warfare defense

vaccine development and licensure schedule, dated 3 October 2000,

was used.

− The GOCO VPF will be built using military construction and a

design-build (i.e., “turn-key”) contracting strategy.

− The acquisition strategy will include competitive award to two

contractors and subsequent performance competition with downselect to one contractor at 35 percent design point.
0101042.doc 7

• Major constraints:

− Assumptions for each vaccine to be produced:

ß Tier 1: Current requirements

• AVA for entire force

• 300,000 Troop Equivalent Doses2 (TEDs) for other

vaccines

ß Tier 2: 3 million TEDs for force protection

• 2.4 million for U.S. forces + 0.6 million for

Commanders Reserve, Other-than-U.S.-forces, and

Canada-U.K.-U.S. Memorandum of Agreement

• Stockpile plus annual requirement for several vaccines

• Basis for the GOCO facility design

ß Tier 3: 300 million TEDs for civilian protection

• Approximation for total U.S. population

• Beyond the baseline operating scope of the GOCO

facility design

− Vaccine production will be as shown in Table 1 and use the three

suites at maximum capacity as needed to fulfill requirements.

− Fermentation with spore-producing bacteria (i.e., AVA) requires a

dedicated production suite.

Preliminary costs for designing, building, and validating the GOCO VPF are

estimated to be $386M ($CY). The LCCE for operations would be approximately

$915M over the 25-year life cycle that equates to an average annual operating cost

estimate of $36.6M. The LCCE for other government costs are estimated to be

$259M ($CY). A preliminary projected schedule is shown in Figure 2.

Figure 2. DoD GOCO VPF Product Schedule

 

2

 Troop equivalent dose is defined as the number of vaccine administrations required to reach the required

immunity. Boosters are not included.

FY02 FY03 FY04 FY05 FY06 FY07 FY08 FY09 FY10 FY11 FY12 FY13 FY14 FY15 FY16 FY17 to FY26

Facility design/build/validate

Smallpox MSIII Cell Suite

Plague MSIII Recombinant Fermentation Suite

Tularemia MSIII Recombinant Fermentation Suite

Anthrax Vaccine Adsorbed Dedicated Spore Fermentation Suite

Botulinum Multivalent MS III Recombinant Fermentation Suite

Next Generation Anthrax Vaccine MS III Recombinant Fermentation Suite

Ricin MS III Recombinant Fermentation Suite

Multivalent Equine Encephalitis Cell Suite MS III

= FDA approval of license amendment for product at this facility
0101042.doc 8

4. A determination, developed in consultation with The Surgeon General, of

the utility of such a facility to support the production of vaccines for the

civilian sector, and a discussion of the effects that the use of such a facility

for that purpose might have on:

(a) the production of vaccines for the Armed Forces; and

(b) the annual cost of operating such a facility.

Relatively early in the process of considering DoD alternatives for vaccine

acquisition, the Department established a Federal Interagency Advisory Group on

the DoD GOCO VPF. Participants, in addition to those from DoD agencies, have

included representatives of the White House [Office of Science and Technology

Policy, National Security Council, Office of Management and Budget], Federal

Emergency Management Agency, Department of Health and Human Services

(DHHS) [National Institutes of Health, Public Health Service, Food and Drug

Administration, Centers for Disease Control and Prevention, and the Office of the

Assistant Secretary for Health and The Surgeon General]. This group, chaired by

the Deputy Assistant to the Secretary of Defense for Chemical and Biological

Defense (DATSD(CBD)), has served as a highly effective and productive forum

for discussions concerning U.S. vaccine acquisition—particularly vaccines for

defense against biological warfare agents—for force health protection and public

health needs for the civilian sector.

The DATSD(CBD) met with The Surgeon General of the United States on

January 5, 2001 to discuss the status and plans for a DoD GOCO VPF for force

health protection against biological warfare agents. They also discussed the issues

posed in point 4, above, particularly, the utility of the GOCO for production of

vaccines for the civilian sector and effects that might have on production of

vaccines for force health protection and facility costs. The Surgeon General has

addressed these points in a letter at Appendix C.

The Surgeon General recognized that biological warfare agents, even if

targeted at a military force, could cause severe, primary or collateral civilian

casualties. He agreed that a GOCO VPF could assure the availability of the

vaccines for fulfilling military needs, as well as eventual use in the civilian sector,

should such a contingency arise. The Surgeon General also observed that civilian

participation could contribute to the successful planning and operation of the

GOCO VPF. The Surgeon General stated that it is important that the GOCO VPF

have sufficient flexibility to accommodate evolving production requirements, both

for new vaccines and for fulfilling future civilian sector needs.

The DoD GOCO VPF will manufacture FDA-licensed vaccines. The FDA

licensure requirements for vaccines intended for both DoD and civilian sector
0101042.doc 9

needs are stipulated in 21 CFR. The Surgeon General noted in his letter that the

lists of biological weapons agents confronting the civilian sector are very similar

to those under consideration by the DoD in its planning for the DoD GOCO VPF.

Vaccines manufactured in the DoD GOCO VPF will be effective when used by

civilian populations for their FDA-licensed indications.

The Department welcomes the continued support and participation of DHHS in

our GOCO VPF planning. We agree that such civilian support and participation

contributes to successful design, construction, and licensed production of vaccines

for force health protection against biological warfare agents. Fulfilling armed

forces vaccine requirements and applying the GOCO vaccine production capacity

to meet civilian sector requirements—beyond those production requirements for

the armed forces—should enhance successful operation and contribute to public

acceptance.

Finally, the DoD GOCO VPF design is intentionally flexible and planned to

accommodate changing production requirements, both in quantity and vaccine

diversity. Annual operating costs for vaccine production are proportional to the

production requirements and until the expanded production requirement is defined,

there is no solid basis for estimating increased annual operating costs. Despite

this, it should be noted that there is a great deal of agreement between cost

estimates developed in the DoD GOCO VPF LCCE and the report by the

independent panel of experts (Appendix B) who place annual operating costs of

vaccine production at between $35M and $50M per vaccine. There may be

economies of scale in expanding the GOCO once it is in licensed production,

rather than in de novo construction for added capacity or product diversity.

5. An analysis of the effects that international requirements for vaccines, and

the production of vaccines in response to those requirements, might have

on:

(a) the production of vaccines for the Armed Forces; and

(b) the annual cost of operating such a facility.

The DoD GOCO VPF would produce vaccines licensed by the FDA. Most

commonly, vaccines licensed by the FDA are acceptable for their licensed

indication in worldwide populations. Some nation states have testing

requirements that are different from, or are in addition to, FDA requirements and

those would have to be addressed on a case-by-case basis. Since the primary

objective of the DoD GOCO VPF would be to produce vaccines to meet armed

forces health protection against biological warfare agents, and since DoD use is

not impacted by other than FDA licensure requirements, there should be no impact
0101042.doc 10

on production for the armed forces. As with the DoD GOCO VPF annual

operating costs to support civilian sector needs, the annual operating costs are

expected to increase in proportion to the size and diversity of the international

vaccine requirements. Unless and until such requirements are characterized,

realistic vaccine production capacity and the associated cost estimates cannot be

provided.
0101042.doc

APPENDIX A

Public Law 106-398 – October 30, 2000

Floyd D. Spence National Defense Authorization Act

For Fiscal Year 2001

Section 218. Report on Biological Warfare Defense

Vaccine Research and Development Programs
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0101042.doc A-1

APPENDIX A

PUBLIC LAW 106-398 – OCTOBER 30, 2000; FLOYD D. SPENCE NATIONAL

DEFENSE AUTHORIZATION ACT FOR FISCAL YEAR 2001

SEC. 218. REPORT ON BIOLOGICAL WARFARE DEFENSE VACCINE

RESEARCH AND DEVELOPMENT PROGRAMS.

(a) REPORT REQUIRED - Not later than February 1, 2001, the Secretary of Defense

shall submit to the congressional defense committees a report on the acquisition of

biological warfare defense vaccines for the Department of Defense.

(b) CONTENTS - The report shall include the following:

(1) The Secretary's evaluation of the implications of reliance on the commercial

sector to meet the requirements of the Department of Defense for biological

warfare defense vaccines.

(2) A design for a government-owned, contractor-operated facility for the production

of biological warfare defense vaccines that meets the requirements of the

Department for such vaccines, and the assumptions on which that design is based.

(3) A preliminary cost estimate of, and schedule for, establishing and bringing into

operation such a facility, and the estimated annual cost of operating such a facility

thereafter.

(4) A determination, developed in consultation with the Surgeon General, of the

utility of such a facility to support the production of vaccines for the civilian

sector, and a discussion of the effects that the use of such a facility for that

purpose might have on--

(A) the production of vaccines for the Armed Forces; and

(B) the annual cost of operating such a facility.

(5) An analysis of the effects that international requirements for vaccines, and the

production of vaccines in response to those requirements, might have on--

(A) the production of vaccines for the Armed Forces; and

(B) the annual cost of operating such a facility.

(c) BIOLOGICAL WARFARE DEFENSE VACCINE DEFINED - In this section, the

term “biological warfare defense vaccine: means a vaccine useful for the

immunization of military personnel to protect against biological agents on the

Validated Threat List issued by the Joint Chiefs of Staff, whether such vaccine is in

production or is being developed.
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1100003

DEPARTMENT OF DEFENSE

ACQUISITION OF VACCINE PRODUCTION

(AVP)

REPORT TO THE DEPUTY SECRETARY OF DEFENSE BY

THE INDEPENDENT PANEL OF EXPERTS

VOLUME I

DECEMBER 2000

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.
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DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 ii

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

EXECUTIVE SUMMARY

By memorandum dated July 20, 2000, the Deputy Secretary of Defense tasked the Director,

Defense Research and Engineering and the Assistant Secretary of Defense for Health Affairs to

jointly contract with a private organization or panel of experts to conduct a comprehensive study

of the Department of Defense (DoD) acquisition of vaccine production (AVP). The study was to

focus on review of the following areas:

• Vaccines to protect Service members against biological warfare threats as well as

infectious diseases.

• A comparison of current Department efforts with best business practices in the

biologics industry, and if/how the Department can leverage the best aspects of the

private sector programs from industry.

• A determination whether the DoD program requires acquisition processes unique from

normal departmental acquisition procedures.

• The development of recommendations for how the Department should best develop and

oversee a vaccine production program.

An independent panel of experts (the Panel) was established and assessed DoD’s AVP

requirements and ongoing programs, management, and acquisition processes against U.S.

vaccine industry best practices.

The Panel found that:

• BW and endemic diseases are proven, high consequence threats to military operational

effectiveness.

• Vaccines are the lowest risk, most effective protection; they enable force projection and

are superior to antibiotics or other treatments.

• DoD’s current AVP approach is insufficient and will fail.

• A new approach can make this program work.

The size and scope of DoD vaccine requirements for force protection are exceptionally large.

DoD requires new vaccines to protect against 15 or more biological warfare (BW) and endemic

diseases. By comparison, vaccines licensed for use in the U.S. protect against about 20 diseases

and Merck & Co., Inc. manufactures 9 licensed vaccines. The size and scope of the DoD

program is too large for either DoD or industry alone. A combined, integrated approach drawing

on industry, DoD, and national scientific strengths and assets is essential.

DoD needs to consolidate and integrate its vaccine research, development, and acquisition

programs for BW defense and endemic disease protection. Success requires a tailored

acquisition model and infusion of technically qualified staff at all levels. A Joint Program

Executive Officer must have responsibility and authority for the program and report to a

designated acquisition executive, a Vaccine Acquisition Executive reporting to the Under

Secretary of Defense (Acquisition, Technology and Logistics). The DoD vaccine acquisition

program should be managed as an Acquisition Category I program and—on an 8 vaccine scale—

requires a $3.2 billion research and development program. A government-owned and contractoroperated vaccine production facility is an essential element of the DoD program. DoD senior

leadership must meet with and solicit industry support for its vaccine requirements.
INTENTIONALLY BLANK.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 iii

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

TABLE OF CONTENTS

Executive Summary........................................................................................................................ ii

1.0 Introduction..........................................................................................................................1

2.0 Scope of Task and General Understanding..........................................................................1

3.0 Industry Best Practices for Vaccine Production ..................................................................2

4.0 DoD Organization, Management, and Capabilities...........................................................10

5.0 Integration of DoD and Industry Vaccine Objectives........................................................15

5.1 Resources................................................................................................................. 16

5.1.1 Market Needs............................................................................................... 16

5.1.2 Size and Scope of DoD Vaccine Requirement ............................................ 17

5.1.3 Capital Investment ....................................................................................... 17

5.1.4 Infrastructure Maintenance .......................................................................... 18

5.1.5 Adoption of Vaccine Industry Product Development Process .................... 19

5.1.6 Multiyear Contract Awards.......................................................................... 19

5.1.7 Commercial Sales of Vaccines .................................................................... 19

5.1.8 Personnel Requirements in Vaccine Discovery and Production.................. 21

5.1.9 GOCO Facility............................................................................................. 21

5.2 Policies..................................................................................................................... 24

5.2.1 Confidentiality ............................................................................................. 24

5.2.2 Management of BW Perceptions and Treaty Compliance Issues................ 24

5.2.3 Use of Non-U.S. Owned or Based Manufacturers....................................... 24

5.2.4 User Acceptance of Vaccine........................................................................ 25

5.2.5 Use of IND Vaccines................................................................................... 26

5.2.6 Vaccine Liability and Indemnification ........................................................ 26

5.2.7 Vaccine License Holder............................................................................... 27

6.0 Findings and Recommendations........................................................................................27

Appendix A Conduct of the Study of Department of Defense Acquisition of Vaccine

Production ...................................................................................................... A-1

Appendix B Generic Industry Process for Biologics Product Development.......................B-1

Appendix C Several Categories of Consideration for Vaccine Discovery through the

Manufacturing Process....................................................................................C-1

Appendix D Briefing – DoD Acquisition of Vaccine Production (Report to the

Deputy Secretary of Defense by the Independent Panel of Experts),

November 29, 2000 ........................................................................................ D-1

Appendix E Acronyms ........................................................................................................E-1
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 iv

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

LIST OF TABLES

Table 1. Facts Bearing on the Problem of DoD’s AVP.............................................................. 2

Table 2. Industry Management Benchmarks .............................................................................. 4

Table 3. Successful Vaccine Acquisition.................................................................................... 5

Table 4. Elements of Vaccine Development............................................................................... 6

Table 5. Business Practices for Product Success........................................................................ 7

Table 6. Industry Benchmark for Human Investment (8 Product Scale).................................... 9

Table 7. Industry Benchmark Cost Estimates for Vaccine Programs......................................... 9

Table 8. Reasons Why DoD AVP Program Is at Risk of Failure ............................................. 13

Table 9. DoD AVP Impediments to Industry ........................................................................... 14

Table 10. Reasons Why DoD AVP Is Considered High Risk by Industry................................. 16

Table 11. Industry R&D Funding Benchmark Estimates (8 Product Scale) .............................. 17

Table 12. Contracting to Capture Industry Interest in DoD AVP............................................... 18

Table 13. BW Threats................................................................................................................. 20

Table 14. Infectious Diseases of Military Importance................................................................ 20

Table 15. Factors in Planning for a GOCO Vaccine Production Facility................................... 22

Table 16. Industry Capital Investment and O&M Funding Benchmark Estimates (8 Product

Scale)........................................................................................................................... 23

Table 17. Elements of a Combined Integrated Approach to DoD AVP..................................... 28

Table 18. Industry-Based Management Model for DoD AVP ................................................... 28

Table 19. Industry-Based Management Philosophy for DoD AVP............................................ 30

Table 20. Summary of Findings and Recommendations by DEPSECDEF Focus Area ............ 32

LIST OF FIGURES

Figure 1. Generic Industry Organizational Model for Managing Vaccines .................................. 4

Figure 2. DoD Management Organization for Biomedical Science and Technology BDP ........ 10

Figure 3. DoD Funds Management Process for BDP.................................................................. 11

Figure 4. Business Model for Assessing DoD’s Compliance with Industry Best Practices........ 15

Figure 5. Current U.S. Licensed Vaccines................................................................................... 26

Figure 6. Industry-Based Management Organization for DoD AVP .......................................... 29
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 1

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

1.0 INTRODUCTION

In response to a memorandum dated July 20, 2000, from the Deputy Secretary of Defense

(DEPSECDEF), the Director, Defense Research and Engineering (DDR&E) and the Assistant

Secretary of Defense (Health Affairs) [ASD(HA)] jointly took action establishing the

independent panel of experts (Attachment II of Appendix A) to review Department of Defense

(DoD) acquisition of vaccine production (AVP). The Panel operated independently of the DoD

and consisted of diverse scientific, manufacturing, and regulatory expertise. It was supported by

the Deputy Assistant to the Secretary of Defense for Chemical/Biological Defense

[DATSD(CBD)] and the Director, BioSystems, Office of the Deputy Under Secretary of Defense

(Science and Technology) [ODUSD(S&T)] and by Science Applications International

Corporation (SAIC) under a contract with the Office of the Director, Defense Research and

Engineering (ODDR&E). The DEPSECDEF requested that the study by the independent panel

of experts focus on the following areas:

• Vaccines to protect Service members against biological warfare (BW) threats as well as

infectious diseases.

• A comparison of current Department efforts with best business practices in the biologics

industry, and if/how the Department can leverage the best aspects of the private sector

programs from industry.

• A determination of whether the DoD program requires acquisition processes unique from

normal departmental acquisition procedures.

• The development of recommendations for how the Department should best develop and

oversee a vaccine acquisition production program.

The summary of the approach and process used in conducting the review and assessment is

provided in Appendix A. This volume summarizes the discussions and findings of the Vaccine

Study Panel. Volume II contains copies of briefings and documents provided to the Panel.

2.0 SCOPE OF TASK AND GENERAL UNDERSTANDING

The scope of the Panel’s review and recommendations regarding the DoD’s AVP was defined by

the DoD sponsors as full life cycle, from discovery [science and technology (S&T)] through

development, manufacturing, production, procurement, storage and distribution, sustainment,

and useful life of vaccines. It included the DoD’s vaccines for force health protection program

areas of biological defense (i.e., medical countermeasures to BW threats) and defense for

infectious diseases of military importance (i.e., medical countermeasures to naturally occurring

diseases, endemic to different areas of the world, that adversely impact health across the full

spectrum of military operations). The salient facts bearing on the problem of DoD’s AVP are

summarized in Table 1.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 2

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Table 1. Facts Bearing on the Problem of DoD’s AVP

 BW and endemic diseases are proven, high consequence threats to

military operational effectiveness

 Vaccines are lowest risk, most effective protection

– Better than antibiotics or other treatments

– Enable force projection

 Current approach is insufficient and will fail

 A new approach can make this program work

Inclusion of vaccines for both the biological defense program (BDP) and the infectious disease

program (IDP), from a force health protection, readiness, and business perspective, had particular

relevance because of the first two facts bearing on the problem. Despite perceptions of some

differences between the BDP and IDP in the areas of threat, resources, industrial base, and

organization and management, vaccines are a unifying technology solution that effectively and

efficiently defeat these threats to the force.

The Panel focused its effort on the best way for DoD to administer, manage, and execute the

DoD AVP, consistent with good medicine, efficiency, business practices, technology, priority,

urgency, and cost. It included, as they apply to DoD and industry, consideration of varying

aspects of:

• threat generation,

• requirements definition,

• investment and execution strategy,

• planning, programming, and budgeting (PPB),

• life-cycle process for vaccines (cradle-to-grave),

• regulatory requirements,

• process for making informed decisions, organization and reporting chains, and

• assigned responsibilities, authority and accountability.

In addition, the Panel considered industry’s process and capacity for manufacturing vaccines, as

well as opportunities (e.g., medical need, shared opportunity, and profit) for DoD to leverage

industry capabilities and engage the commercial vaccine industry in supporting its BDP and IDP

vaccine needs.

3.0 INDUSTRY BEST PRACTICES FOR VACCINE PRODUCTION

The major vaccine manufacturers licensed in the U.S. are Wyeth-Ayerst International, Inc., a

division of American Home Products; SmithKline Beecham; Pasteur Merieux Connaught, a

division of Aventis; and Merck & Co. Inc. The primary drivers behind the major vaccine

industry’s best practices and investment decisions are public health (i.e., medical need for a

particular product); potential profitability (i.e., return on investment); and technological

feasibility (i.e., access to a technology and its maturity). Resolving high priority public health

needs fulfills humanitarian concerns and, in turn, ensures sufficient annual sales to provide a

return on investment and potential for long-term profits. Since the cost (approximately $300 –
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 3

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

$400 million) for the research, development, and clinical trials is similar across vaccines, the

industry wants first to select a medical need for which there will be high acceptability for the

vaccine within the medical community. This is an important difference between industry and

DoD. Although DoD generally has prioritized requirements for vaccines, it does not necessarily

have the option of determining which vaccines it will develop. Resolving medical need to

protect the force and enable force projection is a key DoD consideration. While industry can

choose which needs to address, DoD must address threats.

The market life for older vaccines is 15–20 years [Anthrax Vaccine, Adsorbed (AVA) is

approximately 30 years old]. Newer vaccines are projected to have a market life of 10–15 years.

This is an element in industry’s investment strategy and decision-making process. The $300 to

$400 million is a cost estimate for development of a vaccine that takes 7-12 years (discovery

through licensure) and does not include any associated facility capital investment. Market life is

becoming shorter while development schedules remain relatively fixed and development costs

increase. This translates into potentially dramatic decreases in return on investment.

It is estimated that clinical trials represent 30% - 40% of the total vaccine development cost

necessary to capture every possible observation and to be able to address them to the Food and

Drug Administration (FDA) in terms of demonstrated safety, potency, and efficacy.

Demonstrating safety and efficacy is considered a critical part of the cost of doing business. It

demands extensive quality assurance (QA) and quality control (QC) support as well as rigorous

reporting.

Technology drives the early decision to develop a vaccine, forces early emphasis on process

development, and defines the manufacturing process. As a result, options are tested and

evaluated as early as possible. Maximizing product progress is a common industry goal in

reducing risks and costs. Due to the underlying complexity of the technical processes, once a

decision is made to take a vaccine candidate out of discovery and move forward, industry

intensely manages the product stream from discovery through production and licensure and

brings its full corporate resources to bear on the project. Risks are reduced to a manageable level

prior to making the decision to go forward from the S&T base (i.e., discovery), and industry will

shut a project down if it determines there is a problem. The decision to discontinue is normally

based on feasibility — an analysis of technical risk. Such technical risks are mitigated by

maintaining a robust S&T program of alternative constructs for products in development.

Technology base activities typically receive quarterly reviews while developmental testing

activities are more heavily scrutinized. Scientific and technical decisions account for the major

impacts on vaccine development and licensure costs and schedules.

Decision making (responsibility, authority, and accountability) is vested by corporate executives

in the management team overseeing execution of the process; that is, industry delegates decision

making to the management team collocated with the discovery and development project teams.

A generic representation of the industry model is shown in Figure 1. The management teams are

multidisciplinary, typically led by a scientist with in-depth expertise and experience, and many

establish written agreements or “contracts” with each of the project teams executing the different

components of the overall process. Industry emphasis on individual performance and

accountability is reflected in compensation reviews that commonly incorporate consideration of

both team and individual performance and accomplishment.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 4

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Figure 1. Generic Industry Organizational Model for Managing Vaccines

The management philosophy and approach used by industry, as summarized in Table 2, gives the

management team and project teams maximum flexibility (applying the right people, skills, and

resources during and at any time in the process) and accountability for success. This approach

has proven highly effective and efficient within the industry.

Table 2. Industry Management Benchmarks

 Goal is quality product

 Scientific expertise at every level

 Problem focus for continuing improvement

– Rapid assessment and decisions

 Mitigate risk at every stage

 Commitment to development and production follows successful

discovery phase

 Empowered and accountable management teams

VP Quality

Systems

Directors

S&E

VP Technology

Manager

Project

Directors

S&E

VP Clinical

Studies

Directors

S&E

VP Regulatory

Affairs

Project

Directors

S&E

Board of Directors

CEO and President

VP Vaccines

DIR Operations

Plant Manager

Area Manager

Supervisors

Operators
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 5

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Another of the keys to industry’s success is effective integration of all vaccine life cycle

activities as outlined in Table 3.

Table 3. Successful Vaccine Acquisition

Industry Best Practices effectively integrate:

 Policy

 Product life cycle components

– Research

– Development

– Production

– Licensure

– Sustainment

 Resources

 Management

The generic elements of vaccine development (discovery through production and licensure) used

in industry are depicted in Table 4 and shown in a time-phased manner in Appendix B.

Although specific steps may be carried out or be titled differently, this table provides a succinct

overview of activities in the process. Due to the high technical risks associated with biologicals,

industry generally does not consider transitioning a candidate vaccine from discovery (i.e., the

industry phase corresponding to DoD’s S&T phase) to product development until:

• The candidate has successfully passed Phase 2 clinical trials, and

• Solid progress has been made in the manufacturing process.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 6

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Table 4. Elements of Vaccine Development

Capacity Function Comments

Discovery Research Determine mechanisms of

immunity

Define immunization technologies

In and out of house

Develops pipeline

Vaccine Development

Laboratory Research

Preclinical evaluation of

immunization technology

Refinement of technology

In house: requires state-of-the-art, broadly

based science capability

Vaccine Manufacture

Process Development

Establish technology based

manufacturing process

Optimize process

Produce research lots

Integration of research, manufacturing, and

process engineering

Phase 1 Clinical Trials Determine initial safety and

biologic activity

Intense clinical research program in a

confined environment

Phase 2 Clinical Trials Determine safety and biologic

activity (immunogenicity) in

modest size study group

Established clinical research program in field

site clinic programs

Phase 3 Clinical Trials: A Definitive efficacy, extended

safety

Established clinical research programs,

multiple sites, where disease is prevalent

Manufacturing process

and assay validation

Ensure accuracy of manufacturing

process and product testing

Interactions between quality control, quality

management, research, and manufacturing

programs

Ongoing process and

assay development

Address problems arising in

clinical trials, manufacturing, and

testing

Consistent ongoing dimension of vaccine

development; requires application of state-ofthe-art research capability to problem solving

Facility development Construction and operation of

facility for scaled up manufacture

May occur before consistency lot

manufacture, or for postlicensure change

Process scale up Enhance manufacturing to

commercial levels

Major process engineering issue

Phase 3 Clinical Trials: B Consistency lot evaluation Established clinical research programs in

large field site(s)

Communications with

FDA, Vaccine Advisory

Committee

Define development,

manufacturing, and licensing

requirements

Ongoing throughout development process

Communications with

vaccine recommending

bodies (e.g., AFEB,

ACIP)

Determine potential for vaccine

usage

Determines strategy for clinical trials,

manufacturing scale, and logistics

License application Prepare and submit ~100 volume

document to FDA

Defines in detail every aspect of vaccine

manufacture, testing, preclinical and clinical

evaluation, and the operation of all aspects of

the manufacturing facility; >100FTE, >1yr

Phase 4 Clinical Trials Determine safety of vaccine in

general use

Field epidemiology at site(s) of use

Ongoing process

development

Address issues that arise and

ongoing product quality

Always required to address stability and

related issues, and problems that arise
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 7

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Each vaccine is managed on an individual basis since its associated technologies and processes

tend to be very different from other vaccines. In this regard, a manufacturer would rarely

transition from discovery more than one technology lead for a potential vaccine at a time;

however, every discovery program has multiple backup technologies to fall back on in those

cases where the lead technology may fail. This is true from concept to feasibility analyses

throughout the investigational new drug (IND) process. Further, industry exercises integrated

development production strategies that involve only a limited number of vaccines at any one

time. The major supporting business practices used by industry to maximize the probability of

successfully getting a vaccine to market are identified in Table 5.

Table 5. Business Practices for Product Success

 Product focus, not budget focus

 Funding stability

 Up-front multiyear commitment

 Flexible “reprogramming” authority (dollars and type)

Every vaccine needs a champion and the more champions there are the better the chances of

success. An axiom of the vaccine industry is that success demands that the staff at every level be

“highly” qualified and that they be adequately compensated. Normally there is a discovery

team, not “one inventor” for a product. The discovery team serves in an advisory role during the

manufacturing, testing, and production phase, but they do not lead any of these activities. The

advisory role entails no more than 5% of the discovery team’s time. Industry wants their S&T

discoverers to remain at the bench to the fullest extent possible, as this is where their

contributions will be greatest. Interestingly, industry often allows up to 20% of discoverers’ time

to be spent pursuing independent study and research.

Successful vaccine production is linked clearly with absolute control of the overall process, and

in terms of manufacturing, it is associated with repeating the process over and over – producing

a vaccine on a regular basis. Acquisition strategies that plan production for every third or fourth

year are widely viewed as unrealistic and technically unfeasible. The vaccine manufacturing

process does not lend itself to long breaks in production (i.e., greater than a year) since

manufacturing vaccines entails three interdependent elements – validated process, scientific art,

and team skills. Manufacturing start-up costs can be as high as $20 - $30 million per product

and likely would have to be repeated any time there is a break in production lasting longer than 1

to 2 years. Further, it must be recognized that from an FDA perspective, if vaccines are not

continuously produced so that FDA can inspect at any and all stages of manufacturing, then

compliance and license problems are more likely to occur.

The vaccine industry was among the first to try outsourcing. Companies having the capacity and

capability tried outsourcing manufacturing but have since pulled these operations back in-house.

Unlike outsourced manufacturing of chemical pharmaceuticals, outsourcing of vaccine

manufacturing was found to be fraught with difficulties, inordinate process control risks, and

added overall costs. As a result, the major vaccine producers limit or do not outsource

manufacturing at all. Most do not believe they will be able to operate as virtual companies for

the foreseeable future. Outsourcing for other non-manufacturing activities, such as conduct of

clinical trials, is possible and economically feasible.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 8

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

The pharmaceutical (i.e., drug) industry has had excellent success with outsourcing its

manufacturing processes. This is thought to be due to the straightforward nature of the chemistry

in the manufacturing processes for drugs. The vaccine industry does much in-sourcing (inlicensing), while looking outward for ideas (e.g., buy into patents and collaborative partners).

Some of the small biotechnology companies, by necessity, do outsource steps in their processes,

and this is likely to continue. It is critical that DoD carefully assess the risk associated with any

strategy for the AVP that includes any major element of outsourcing.

Pharmaceuticals (drugs) and biologics (vaccines) are different and the biologics investment and

risk are incompatible with outsourcing as a preferred option. The unique problems associated

with process control during the manufacturing of vaccines provide a basis for industry’s

reluctance to outsource. Industry’s experience in three areas underscores their concern.

• Late changes to the vaccine manufacturing process may require additional clinical trials

for safety and efficacy.

• Taking a validated process from one vaccine facility and trying to replicate it in another

facility is a major undertaking, requiring revalidation of product safety and equivalence.

• Renovating and modernizing an old vaccine facility can take several years and requires

revalidation of product safety and equivalence.

A wide variety of difficult scientific issues need to be addressed in a coordinated and timely

fashion in the course of vaccine development. In general, precedents established previously in

the course of addressing scientific problems associated with development of other vaccines are

of little relevance to development of a new vaccine. In contrast, drug development tends to be

much more standardized.

Industry considers people and process to be the cornerstones of successful vaccine projects. The

benchmark standard of investment in human resources for an 8 product (vaccine) scale is 2,500

people with exceptional and specialized skills. This includes all aspects of the vaccine process

from discovery through production and licensure. Table 6 provides a summary of the industry’s

benchmark investment in human resources. There is a national and international scarcity of

personnel with the requisite skills and expertise needed by the vaccine industry. As a result, the

industry provides extremely attractive compensation packages in their efforts to attract and retain

the most qualified. Recent college graduates can have starting salaries of $40,000 to $50,000

and individuals with process validation experience are attaining salaries in the $100,000 to

$120,000 range. Industry provides continuing education and training programs and expects their

senior technical production personnel to be qualified in several areas of vaccine production (e.g.,

manufacturing, validation, and regulatory affairs).
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 9

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Table 6. Industry Benchmark for Human Investment (8 Product Scale)

 2,500 people

 Exceptional and specialized skills

– Scarce national pool

 Competitive compensation

 Special human resources programs

– Recruit, train, and retain

Industry’s benchmark estimate of costs associated with the major components of a vaccine

program is summarized in Table 7. The estimate covers the major areas [e.g., research and

development (R&D) and capital investment cost for facility] of consideration supporting a

vaccine program. Process and facility improvement, an integral and critical part of industry’s

investment, is estimated at 5%-10% of the operational budget per year. Industry considers this

cost in its market analysis and expects to fully recoup this investment from their sales of

vaccines. The R&D cost estimate of $300M-$400M includes discovery through production and

licensure of a single vaccine. The cost estimate of $370M to build and equip a vaccine facility

includes the required initial production, laboratory, and support suites to produce three to four

vaccines.

Table 7. Industry Benchmark Cost Estimates for Vaccine Programs

Element Cost/Product

R&D ~$300M - $400M

Facility capital costs ~$370M initial*

Additional production, labs, and support ~$75M - $115M**

Manufacturing Operations and Maintenance ~$30M - $35M/year *First 3 vaccines

**For each vaccine beyond initial 3-4

The FDA has changed a great deal over the last 10 years. Personnel from the FDA’s Center for

Biologics Evaluation and Research (CBER) used to conduct pre- and postlicensure inspections.

Due to concerns with the regulatory oversight process, the FDA recently established Team

Biologics, principally consisting of field inspectors, which now conducts biannual compliance

(postlicensure) inspections. In the process of change, it is commonly perceived that the focus

shifted from identifying problems and finding solutions for their resolution to one of establishing

absolute compliance backed up by detailed record keeping. A warning letter that is issued by the

FDA to a facility today is taken very seriously by the industry. In fact, some individuals view

receipt of a warning letter as the potential end of their career. The vaccine industry considers the

regulatory environment to be extremely demanding but a necessary part of business and a part

of their established best business practices.

The research, development, and acquisition (RDA) process for vaccines — regardless of whether

it is practiced by the private sector or DoD — is extraordinarily complex, highly technical and

regulated, and difficult to articulate to those outside the vaccine business in a manner that

enables them to grasp the complexity, interrelationship, and dependencies of the steps in the

process (Figure in Appendix B and Table 4), let alone the overall problems encountered in

getting a potential vaccine from discovery to market. The difference is that vaccines as biologics

are produced by microbial or mammalian cells that require absolute control over the myriad
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 10

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

aspects of production (as compared to the relative ease of control of chemical reactions and

purification of drugs). In the absence of such understanding, it is difficult to fully assess the

magnitude of the impact of regulatory requirements and scientific problems encountered during

the process (e.g., preclinical testing, clinical trials, and scale-up manufacturing) on a program.

Further, it may preclude meaningful interpretation and appreciation of why one vaccine succeeds

and another fails, and hinders informed application of lessons learned in strategic and tactical

decision making.

4.0 DOD ORGANIZATION, MANAGEMENT, AND CAPABILITIES

Although centralized program oversight in DoD is laudable and important, the number of

organizational entities that are directly influencing the biomedical S&T BDP and IDP [U.S.

Army Medical Research and Materiel Command (USAMRMC)] seems unnecessary and

counterproductive (Figure 2). The same is true for the Joint Vaccine Acquisition Program

(JVAP). For example, DoD organizations influencing these programs include DDR&E,

DUSD(S&T), DATSD(CB), Defense Threat Reduction Agency (DTRA), ASD(HA), Joint

Nuclear, Biological, Chemical (JNBC) Defense Board, Joint Services Integration Group (JSIG),

Joint Services Materiel Group (JSMG), The Surgeons General, and Joint Program Office for

Biological Defense (JPO BD). Further, the resultant organization has seemingly fragmented the

DoD vaccine RDA program. It has placed leadership decision making for medical BDP products

largely in organizations that lack the requisite level of medical and technical expertise.

Similarly, leadership decision making for medical ID vaccines is in organizations that are

missing the requisite level of Defense materiel acquisition expertise. Only a very limited number

of offices have effectively integrated expertise in medical and technical matters with the requisite

levels of Defense acquisition expertise. This impacts on the seamless delivery of vaccines in

DoD.

Figure 2. DoD Management Organization for Biomedical Science and Technology BDP

CJCS

CSA

DCSOPS

CG, TRADOC

CG, AMEDD C&S

TSG

MAMP

JROC

ASD(HA)

ASA(MR&A)

TSG

USD(PR)

MRSP

USD(AT)

DAE

DDR&E

Dir, Env & Life Sciences

ATSD(NCB)

Dep, Counterproliferation

ASA(RDA)

AAE

DAS-R&T

CG, USAMRMC

SECDEF

DEPSECDEF

CINCs

JNBC 

Defense Board

JSMG -- JSIG

ASBREM

Committee

JTCGs

JWSTP

DTAP

ASTMP

DAB

MAISRC

ASRC

AMAISRC

MEDSYS

MDA

MARP

AMP

TFSC

Deputy for

Medical 

Systems

CJCS

CSA

DCSOPS

CG, TRADOC

CG, AMEDD C&S

TSG

MAMP

JROC

ASD(HA)

ASA(M&RA)

TSG

USD(PR)

MRSP

REQUIREMENTS

USD(AT&L)

DAE

DDR&E

DUSD(S&T)

ATSD(NCB)

DATSD(CBD)

ASA(ALT)

AAE

DAS-R&T

CG, USAMRMC

SECDEF

DEPSECDEF

CINCs

JNBC 

Defense Board

JSMG -- JSIG

ASBREM

Committee

JTCGs

JWSTP

DTAP

ASTMP

DAB

MAISRC

ASARC

AMAISRC

MEDSYS

MDA

MARP

AMP

TFSC

Deputy for

Medical 

Systems

ACQUISITION
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 11

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

With regard to the organization and management, there is fragmentation of the DoD AVP within

and across the Office of the Secretary of Defense (OSD) and the Services. Examples include:

• BDP. OSD controls the funding for BDP vaccines, and DATSD(CBD) has oversight of

the full life cycle of the BDP, the Army is the Executive Agent for the BDP, the S&T

aspects of the BDP vaccine program are executed in the USAMRMC, advanced

development through production is executed through the JPO BD, and procurement of

resultant products is with Defense-wide procurement dollars. JPO BD authority is

diluted by the oversight structure and has no effective reprogramming authority. The

seemingly complex process for managing BDP funds is depicted in Figure 3. There is

limited biomedical expertise and knowledge in the JPO BD reporting chain, and in the

JSIG, JSMG, and JNBC Defense Board. There is no qualified medical authority over

BDP vaccine decisions.

Figure 3. DoD Funds Management Process for BDP

• IDP. The DUSD(S&T) has oversight of the S&T program for IDP vaccines. There is no

OSD-level assigned responsibility for the program beyond S&T, with resultant

consequences for proponency, oversight, and management of associated development and

acquisition activities. The Army is the Lead Agent and resources the program while

USAMRMC executes the Lead Agent program responsibilities (S&T through production)

through the Services’ biomedical laboratories and contracts. Procurement of resulting

DATSD (CP/CBD)

• Issues BES preparation instructions

• Issues funds suballocation instructions

• Approves BES and Budget Allocation 

Instructions

• Submits BES/PB

• Approves reprogramming actions

• Oversees program execution

• POM/BES/PB

• Funds Distribution Information

• Execution Reports

• Reprogramming 

Recommendations

• BES/PBD Documentation

• Reprogramming Recommendation

• BES/PB Inputs

• Execution Reports

• $ - MIPR/ 

Suballocations

• BES/PB

Instructions

DTRA Budgeting

• Suballocates Funds IAW PB 

(DTRA/FM)

• Coordinates/Approves 

reprogramming actions (DTRA/CB)

• Monitors program execution

Operating Agencies

• Distribute Funds to performers

• Participate in POM/BES/PB 

preparation

• Report program execution

• Reprogram within Service allocation

• Request reprogramming authority

Performers

• Execute programs

• Report execution status

• Prepare BES/PB inputs

JSMG

• Distributes POM/BES/PB guidance

• Consolidates POM/BES/PB inputs and resolves 

Issues

• Prepares/updates POM/BES/PB documentation

• Coordinates funding adjustments

• Makes reprogramming recommendations

• Maintains supporting database

JNBCDB Secretariat

• Prepares BES/PB in coord with JSMG

• Reviews and analyzes program execution

• Prepares funds distribution information

• Makes reprogramming recommendations

• Reports execution status to DATSD 

(CP/CBD)

• Updates database

JSMG Hand Book of Standard Operating Procedures, Fig IV-I, Page 19 

Database Updates

BES/PB Submission

• Budget Suballocation 

Instructions

• Reprogramming 

Instructions

$ - Appropriation

$ - Funding Document

$ - PBAS Execution Reports

Execution Reports

BES/PB Instructions

• POM/BES/PB

• Reprogramming 

Requests • BES/PB 

Instructions

POM/BES/PB

Instructions

Congress

OSD Comptroller

...

DATSD (CP/CBD)

• Issues BES preparation instructions

• Issues funds suballocation instructions

• Approves BES and Budget Allocation 

Instructions

• Submits BES/PB

• Approves reprogramming actions

• Oversees program execution

• POM/BES/PB

• Funds Distribution Information

• Execution Reports

• Reprogramming 

Recommendations

• BES/PBD Documentation

• Reprogramming Recommendation

• BES/PB Inputs

• Execution Reports

• $ - MIPR/ 

Suballocations

• BES/PB

Instructions

DTRA Budgeting

• Suballocates Funds IAW PB 

(DTRA/FM)

• Coordinates/Approves 

reprogramming actions (DTRA/CB)

• Monitors program execution

Operating Agencies

• Distribute Funds to performers

• Participate in POM/BES/PB 

preparation

• Report program execution

• Reprogram within Service allocation

• Request reprogramming authority

Performers

• Execute programs

• Report execution status

• Prepare BES/PB inputs

JSMG

• Distributes POM/BES/PB guidance

• Consolidates POM/BES/PB inputs and resolves 

Issues

• Prepares/updates POM/BES/PB documentation

• Coordinates funding adjustments

• Makes reprogramming recommendations

• Maintains supporting database

JNBCDB Secretariat

• Prepares BES/PB in coord with JSMG

• Reviews and analyzes program execution

• Prepares funds distribution information

• Makes reprogramming recommendations

• Reports execution status to DATSD 

(CP/CBD)

• Updates database

JSMG Hand Book of Standard Operating Procedures, Fig IV-I, Page 19 

Database Updates

BES/PB Submission

• Budget Suballocation 

Instructions

• Reprogramming 

Instructions

$ - Appropriation

$ - Funding Document

$ - PBAS Execution Reports

Execution Reports

BES/PB Instructions

• POM/BES/PB

• Reprogramming 

Requests • BES/PB 

Instructions

POM/BES/PB

Instructions

Congress

OSD Comptroller

...
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 12

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

products is made with Operations and Maintenance, Army (OMA) dollars to fulfill Army

requirements. Each service specifies its own vaccine requirements for protection against

infectious diseases and is responsible for their vaccine procurements. The USAMRMC

provides biomedical matrix support to the Joint Vaccine Acquisition Program, Project

Management Office (JVAP PMO).

• The BDP is managed under Defense Acquisition Board oversight as an acquisition

category (ACAT) I program while the IDP is managed as an ACAT IV non-major

program.

Within DoD, the varying degrees of experience, multiple organizations with program

responsibilities, associated levels of oversight [e.g., Congress, OSD, Services, and Major

Commands (MACOMs)], decision making, reporting requirements, and PPB structure and

system do not lend themselves easily to the streamlined process and flexibility used by industry in

taking a candidate vaccine from discovery to market. Hence, there is high risk in DoD’s current

approach to vaccine acquisition. Further, the scope of the BDP AVP and associated schedule of

vaccine procurement raised questions of practical feasibility. The investment strategy is not one

that is consistent with industry best practices and raises questions about whether the risks

associated with such a strategy were fully explored or understood, and if so, how they were

mitigated. Given industry’s success with extremely short oversight and decision-making chains

of responsibility and accountability, the DoD must reexamine its diversity in structure for

overseeing, managing, and executing its vaccine program.

The threat issues and associated problems identified during and following the Gulf War deserved

congressional and OSD scrutiny. There have been many valuable lessons learned as a direct

result of this scrutiny. It appears, however, that the organization put in place by DoD to “fix” the

BDP AVP issues may in fact have become an impediment to efficient and effective vaccine

program management, execution, and success. There is an identified threat list to support the

BDP, and the IDP would benefit from a similar threat list. Since disease threats, regardless of

source (e.g., BW and ID), can have catastrophic impact on military operations, an integrated list

of BW and ID threats deserves consideration in planning, proposing, and budgeting for the most

urgent medical vaccine needs.

DoD’s practices for managing its vaccine programs contrast sharply with industry’s best

practices (Section 3, Table 2) and pose some inherently high risks to success. Factors

contributing to the high risk nature of the DoD approach are summarized in Table 8. It is

contrary to the vaccine industry’s well-established business success model that ensures a single

empowered and accountable individual (project manager) in charge of program, focused (nondiffuse) cross-functional management, and a clear picture of the medical need. DoD practices

diffuse management, making it difficult to establish clear lines of responsibility, authority, and

accountability. In addition, the DoD lacks the level and depth of scientific oversight and talent

needed to manage and execute the vaccine programs. This is exacerbated by a relatively scarce

national pool of exceptional and specialized expertise and DoD’s noncompetitive compensation

packages.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 13

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

The DoD BDP vaccine acquisition strategy, utilizing a prime systems contractor (PSC) with

outsourcing for components of the manufacturing process via multiple subcontracts, differs from

that normally followed in the vaccine industry. It does not mean, however, that this strategy

won’t work. Rather, it may experience considerable delays and must have more intense

technical oversight if it is to be successful. Simply stated, the DoD BDP vaccine acquisition

strategy is considered a high-risk approach.

Table 8. Reasons Why DoD AVP Program Is at Risk of Failure

 Approach is contrary to business success model

– No one in charge

– Diffuse management

– Fragmented program

 Lack of integration from discovery through licensure

 Lack of essential scientific oversight and talent

 Insufficient capture of industrial base

 Goals and dollars do not match

The expertise within DoD to address DoD’s vaccine needs appears to have become fragmented

and difficult to sustain, with the preponderance of expertise resident within the Army and Navy

biomedical research communities. The uniformed biomedical scientist has historically been a

major participant and contributor in the DoD vaccine research, development, test, and evaluation

(RDT&E) process (e.g., leadership, management, and program execution). This seems to have

changed with abolishment of the draft, and the military downsizing (1980s and 1990s) wherein

priority has been placed on warfighter and health care delivery personnel authorizations.

Uniformed biomedical scientists now routinely leave the services to sustain their professional

growth and opportunities or take on a diversity of nonbench and non-RDA assignments to

remain competitive from a promotion perspective. During the past 10 years, not a single military

biomedical scientist has been promoted to the rank of a Flag Officer. This reflects fewer

opportunities for biomedical scientists to reach senior leadership positions where their expertise

and experience can benefit DoD, and is another disincentive for remaining in the military.

Further, the civilian biomedical S&T workforce is relatively stagnant with long years of service,

and recruitment and retention of replacements with the competencies needed to address DoD’s

vaccine RDA needs are extremely challenging. The DoD compensation and benefits package for

civilians is not competitive with industry. The national pool of required biomedical S&T

expertise is limited and extremely expensive. While some companies have had success in

recruiting qualified personnel for the vaccine industry, DoD in many cases, simply cannot

compete with the biotechnology firms, biopharmaceutical industry, or academia for the very best

talent under existing compensation constraints and career opportunity. The DoD is experiencing

difficulty recruiting and retaining required military and civilian biomedical scientists, and has

lost a critical mass of senior uniformed scientists that were well founded in the DoD biomedical

RDA process.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 14

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

There is a general lack of integration in and across the DoD vaccine programs, from discovery

through licensure. The USAMRMC has a pilot plant at Walter Reed Army Institute of Research

(WRAIR) that supports the military infectious disease vaccine effort and the JVAP uses the PSC

to satisfy its biological defense pilot plant vaccine production needs. Additionally, the JVAP and

U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) have used the

National Cancer Institute (NCI) pilot lot production facility located at Fort Detrick, Maryland,

and the National Institute of Allergy and Infectious Diseases (NIAID) has used the pilot

production facility at WRAIR. While this may seem curious, it underscores the technical

necessity of integrating the discovery and development phases and the importance of proximity

to these processes. Both WRAIR and USAMRIID have strong S&T programs supporting the

IDP and BDP, respectively. Industry best practices for success mandate integration of policy, all

elements of a product’s life cycle, resources, and management as summarized in Table 3.

It is clear that the DoD has not had a successful strategy or commitment to effectively capture

the vaccine industrial base. The key existing impediments to industry taking on DoD’s vaccine

needs are summarized in Table 9.

Table 9. DoD AVP Impediments to Industry

 Size & scope of program

 Industrial base at full capacity

 Idle manufacturing

 Risk to industry

– Efficacy risk

– Program stability

– Perceptions

– Political

 Defense procurement practices

Finally, the DoD’s goals for the AVP do not match the programmed and budgeted resources.

Industry maintains a robust discovery base and commits itself to full and stable resources when it

transitions a lead candidate from discovery to development and production. Benchmark costs

associated with vaccine discovery, production, facilities, and maintenance in industry were

discussed in Section 3 and summarized in Table 7.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 15

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

A best business assessment model was used to evaluate the degree of DoD’s compliance with

industry’s best practices for managing and executing vaccine programs (Figure 4). The rationale

for the assessment of DoD’s compliance is provided in the figure.

Figure 4. Business Model for Assessing DoD’s Compliance with Industry Best Practices

5.0 INTEGRATION OF DOD AND INDUSTRY VACCINE OBJECTIVES

Partnering with DoD to produce vaccines is considered a high-risk venture by industry. Some

of the reasons for this industry perspective are identified in Table 10. Industry’s existing and

projected vaccine streams are considered to be strong and growing, with few exceptions. If

industry takes on development and production of a DoD vaccine, it will have to displace

medically needed, competitive and profitable products – an industrial base vaccine capacity issue

– that market analysis demonstrates will satisfy a public health need, grow and provide a

reasonable return on investment. In this regard, DoD will need to fulfill industry’s needs and

expectations. Vaccine manufacturing companies have to grow and growth is more predictable

and easier to manage as a Company initiative than one in support of a DoD vaccine initiative.

Industry Best Practices Assessment of DoD Rationale for Assessment

Integrated-Discovery

Through Licensure Piecemeal process

Scientific Talent Good S&T, inadequate development and production

Technical Qualifications of

Management Vaccine Acquisition ≠ Weapons System Acquisition

Management Focus and

Accountability Fragmented and Multilayered below DEPSECDEF

Funding Stability Annual allocation and frequent decrement drills

Funding Commitment Development/Acquisition not funded following

discovery

Flexible Reprogramming Limited by Congress

Focus on Product Quality Goal ; Execution

R

R

Y G R

R

R/Y

R/Y

R/Y

R

G

Y

R/Y

= Green - Full Compliance

= Yellow - Moderate Compliance

= Red/Yellow - Low Compliance

= Red - No Compliance (High Risk)

Y
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 16

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Table 10. Reasons Why DoD AVP Is Considered High Risk by Industry

 Instability of DoD programs, associated resources, and commitment

 DoD acquisition model and resource system PPB, as well as associated

categories of funds, do not align with industry’s best practices for vaccine

discovery and production

 Industry’s experience with DoD’s unwillingness to resource infrastructure

and process sustainment costs associated with vaccines unique to DoD

 DoD’s episodic capacity requirements and associated risks in maintaining

capability

 DoD acquisition process that seems to emphasize budget, not quality

 Difficulties with and shortcomings of Defense procurement practices

 Proposal preparation and submission costs and processes

 Government regulations [e.g., cost accounting and National

Environmental Policy Act (NEPA)]

 Public perceptions (e.g., mistrust) of DoD

The DoD must acknowledge industry practices and factors that motivate industry, capture

industry interest and incentives, and invest its own corporate resources in the process if it has any

hope of involving the major and successful industrial vaccine manufacturers in solving its

vaccine requirements. The Panel is confident that many leaders in the vaccine industry are

willing to help DoD and will not be opposed to DoD building its own vaccine production facility

once they are familiar with DoD’s requirements and AVP program rationale. With regard to

capturing industry’s interest and willingness to address DoD’s vaccine requirements, the

following resource and policy-related topics that impact potential incentives are offered for

consideration. They represent a critical aspect of an integrated strategy to resolve DoD’s vaccine

requirements.

5.1 Resources

5.1.1 Market Needs

It is important for DoD to market to the public health needs that industry views as important

whenever possible. The industry would likely have interest in vaccines to prevent diseases of

high public health impact [e.g., malaria, Human Immunodeficiency Virus (HIV), and perhaps

hepatitis E and smallpox]. A single manufacturer probably would not want to take on more than

one of these vaccine needs at a time. They already have an existing and projected stream of

scheduled vaccines to meet customer needs and company goals. Further, the staffing and

production capacity support their planned vaccine schedules, and would not generally support

vaccine needs beyond this capability. If the medical need were perceived as important enough to

industry, they might partner with DoD to accommodate a DoD vaccine requirement. There may

also be specific vaccine-related technologies that would capture the interest of industry.

Regardless, the DoD would need to carefully market their specific needs to industry. In this

regard, previous DoD Requests for Proposals (RFPs) have not worked well in the vaccine

industry – because they go in at the wrong level or have an approach that is inconsistent with

industry’s experience for success. For example, the JVAP solicitation was considered by many

in industry to be “way too big” – it had too many products being scheduled over too short a
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 17

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

timeframe. The number of products and schedule were simply viewed as very “high” risk and

did not capture industry interest.

5.1.2 Size and Scope of DoD Vaccine Requirement

The scope of the DoD vaccine requirement is very substantial by any measure. The BDP

requires new vaccines to protect against 10 or more BW threat agents and at least 5 new vaccines

are needed to protect against endemic diseases of military importance. Considering that vaccines

are licensed in the U.S. to protect against about 20 different diseases, the DoD requirement for

approximately 15 new vaccines represents a staggering technological undertaking. The overall

requirement by comparison is larger than that of the vaccine operations of Merck & Co. Inc.,

which produces 9 vaccines. The Panel used a scale of 8 vaccines for estimating the resources

needed for the DoD vaccine program. The DoD program operating at this scale requires about

$3.2B in R&D funds. The assumptions for these rough-order-of magnitude estimates are shown

in Table 11. Given that industry has virtually no excess capacity, it is clear that the size and

scope of the DoD vaccine program itself preclude even major manufacturers as a single source of

DoD vaccines.

Table 11. Industry R&D Funding Benchmark Estimates (8 Product Scale)

 R&D Funds − $3.2B

− ~8 successful vaccines (7-12 years each)*

− ~$300 - $400M/product R&D to licensure

− ~2 products/year to start

− ~4 products/year at year 4

− ~8 products/year when mature

*BD and MIDRP require >8 vaccines total; study scale was 8 vaccines

5.1.3 Capital Investment

The vaccine industrial base is operating at near full capacity and the major manufacturers have

no reason to invest in expanding that capacity beyond that needed to support their vaccine

schedule. Adding capacity requires significant capital investment and it can take 3 to 5 years to

get new or modernized facilities operational and processes validated for facility and product

licensure. The financial cost of failure and rewards for success are great and industry invests its

capital accordingly.

The DoD has a need for many vaccines that have limited potential for marketability elsewhere.

Each of these vaccines will need a dedicated production capability. It is possible that products

that use similar production technologies can be manufactured in the same facility; however, most

products will require unique production technologies and a dedicated production suite and/or

facility.

In the vaccine industrial environment, incentives are needed for successful partnering between

DoD and a vaccine manufacturer. Such incentives include creative capitalization and

guaranteed product demand and revenue streams. If DoD demonstrates a long-term
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 18

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

commitment to making a capital investment to expand the industrial base vaccine capacity,

industry will likely respond. For example, DoD could target selected expansion of industry’s

capacity by providing the fiscal resources, under competitive contracting, for major

manufacturers to design, build, and equip a modular-type facility on their premises for the

production of certain vaccines to meet a DoD requirement. This is one of the least intrusive

approaches and has the advantage of drawing on the manufacturer’s resident expertise for

managing and producing vaccines and would minimally affect the investment concerns of

company shareholders. Some of the important elements of incentive-based contracts that would

facilitate industry interest in participating in DoD’s AVP are summarized in Table 12.

Table 12. Contracting to Capture Industry Interest in DoD AVP

 Longest multiyear contract possible

 Government-provided facility

 Incentive-based contracts

– Award fee

– Industrial R&D

– Intellectual property to contractor

– Third-party sales

5.1.4 Infrastructure Maintenance

The DoD cannot expect industry to invest its resources to maintain the infrastructure (e.g.,

facilities, equipment, and personnel) or modernize its facilities in order to meet DoD vaccine

needs. Lessons learned demonstrate that such expectations inevitably lead to a loss of capability

and source of vaccines. For example, Wyeth Laboratories manufactured Adenovirus Vaccines

(Types 4 and 7) for DoD, the sole customer for the vaccines. When DoD determined it would

not make the investment in renovations of the outdated facility necessary to continue production,

Wyeth Laboratories made a decision in 1995 to discontinue manufacturing. As a direct result,

the vaccine supply ran out, the DoD has not found an alternative supplier, and there has been a

resurgence of acute respiratory disease epidemics in military (Air Force, Army and Navy) and

Coast Guard trainees due to adenoviruses. Unfortunately, the prospects of remedying this force

health protection problem in the near to mid-term are not good.

The requirement to sustain a vaccine facility infrastructure and provide for facility modifications

(e.g., to meet regulatory compliance requirements) should not be underestimated. Failure to

fully plan for continuing these activities will be disastrous for the DoD vaccine program, with a

loss of production capability and years to get a process revalidated and a facility licensed by the

FDA. Hence, infrastructure and modernization planning and resourcing must be integral parts of

the overall DoD vaccine acquisition strategy.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 19

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

5.1.5 Adoption of Vaccine Industry Product Development Process

It may well be to DoD’s benefit to carefully consider industry’s successful approach to vaccine

development and not, therefore, place burdensome constraints on their process. The vaccine

industry uses a process that reduces S&T-related and manufacturing process risks early, before

a decision is made to take a candidate forward for development, manufacturing, and marketing.

Decision making is vested with the management team charged with overseeing the process to get

the product manufactured, licensed, and to market. Once a decision is made to take a product

forward, the management team intensely manages the project teams working the various steps in

the process (e.g., manufacturing, clinical trials, and regulatory) and plans on achieving licensure

of the product within 3-6 years. INDs for vaccine candidates have a success rate of 20% or less

and the resources required to carry a product to market are enormous. Estimates for the

discovery, development, manufacturing, and testing required to achieve licensure of a single safe

and efficacious vaccine are estimated at $300 - $400 million over 7 to 12 years. Rarely would

industry consider transitioning a candidate vaccine out of discovery (i.e., the industry phase

corresponding to DoD’s S&T phase) before it has successfully passed Phase 2 clinical trials and

solid progress has been made in the manufacturing process. The technical risks are otherwise

considered too high. The DoD should be aware of the critical nature of the integrated life cycle

development approach to vaccines. This approach involves a commitment to long-term

development of a vaccine, once a candidate transitions from discovery to development and

production.

5.1.6 Multiyear Contract Awards

A key strategic incentive for industry is the guarantee from DoD of a continued product

production requirement and associated revenues through provisions utilizing multiyear contract

awards. This may take statutory relief but is absolutely necessary in order for industry to

maintain the manufacturing proficiency, personnel, and level of expertise needed to manage and

produce a particular vaccine. The vaccine manufacturing control process does not lend itself to

extended breaks in production since the process involves three interdependent elements –

validated process, scientific art, and team skills and proficiency. If the acquisition strategy for a

vaccine results in extended breaks in vaccine production, the art, technical skills, and proficiency

required for a validated process will be compromised, if not altogether lost.

5.1.7 Commercial Sales of Vaccines

Vaccines are currently the most effective and practical way of protecting an at-risk population

from a BW or ID threat. From a readiness perspective, vaccines are an enabler of force

projection. Accordingly, there is a high probability that foreign military forces will want to

acquire DoD-developed vaccines.

With regard to vaccines that generally have unique utility (e.g., biological defense) to the DoD,

there may be some policy (e.g., DoD and State Department) limitations on the global sales of

such vaccines. In terms of DoD, this most likely would be associated with vaccines that are

developed and manufactured with DoD’s RDA resources. The DoD does consider potential

vaccine requirements for joint operations with U.S. allies; however, it does not incorporate the

total vaccine requirement of its allies in its acquisition strategy. This does not preclude
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 20

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

consideration of such requirements where the sale of vaccines to military allies is contemplated.

Depending on U.S. national policy for defense preparedness requirements of its home front, there

may be a rather large market requirement for biological defense vaccines. The spectrum of BW

threats for which vaccines are needed is represented in Table 13.

Table 13. BW Threats

 Smallpox

 Anthrax (existing product)

 Anthrax (next generation product is desired)

 Plague

 Venezuelan Equine Encephalitis (VEE), Western Equine Encephalitis

(WEE), and Eastern Equine Encephalitis (EEE) combined

 Coxiella burnetii (Q fever)

 Tularemia

 Botulinum toxin A, B, C, E, F

 Staphylococcal Enterotoxin B (SEB)

 Ricin

 Brucella

 Others

The ID threat to the military force depends on the diseases endemic to the particular area of

deployment. History has shown that when troops are deployed to new geographic areas the

probability of disease outbreaks is high, with high risk to decisive military operations. Vaccines

that are developed by DoD to protect U.S. Forces from endemic infectious diseases during

deployments throughout the world may also have a potential commercial sales market,

depending on the fiscal strength of the country involved. Further, the United Nations

International Children’s Emergency Fund (UNICEF) and other humanitarian support efforts may

want to purchase such vaccines when they become available. The IDP needs vaccines to protect

against a wide spectrum of threats such as those shown in Table 14.

Table 14. Infectious Diseases of Military Importance

 Malaria

 Shigellosis (and other enteric bacterial infections)

 Dengue fever

 HIV

 Hepatitis E

 Others

With few exceptions, there are only very limited worldwide public health requirements for those

vaccines that are most needed by the BDP and IDP. Generally, those countries that might have

the greatest need are also those least able to afford large vaccine procurements. For example, a
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 21

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

plague vaccine developed for the BDP might be effective against endemic plague outbreaks such

as occurred recently in India. In such an instance, the U.S might be asked to provide the vaccine

as a humanitarian initiative. As noted above, it is also likely that as vaccines are licensed by the

DoD, both foreign military sales and sales for protection of indigenous populations and

dependents of military service men and women will become an area of increased potential for

commercial sales. Realization of such potential is confronted by both the relatively small size

and non-recurring nature of foreign military vaccine requirements. Additionally, DoD would not

normally conduct clinical trials to support product use by non-DoD personnel, people outside of

the age range of 18-50 years. The absence of such data could be expected to restrict the

commercial sales potential of DoD vaccines.

DoD should clarify its policy on industry rights to foreign military sales of BDP and IDP

vaccines, domestic civilian use of BDP and IDP vaccines, and international and domestic

commercial sales of IDP vaccines. In this way, industry can estimate potential market size in

reaching a decision whether or not to develop a DoD vaccine.

5.1.8 Personnel Requirements in Vaccine Discovery and Production

The importance industry places on having the right people, the right technical skills, the right

depth of expertise, and the right compensation packages to optimize success is reflected in one

major manufacturer’s workforce consisting of approximately 2,500 individuals dedicated to the

management, discovery, process development, manufacturing, testing, production, and related

regulatory support of an average of eight products. That number exceeds the total authorized

personnel strength of USAMRMC in support of its biomedical RDT&E program activities for

IDP, BDP, Military Operational Medicine, Medical Chemical Defense, Combat Casualty Care,

and Congressionally Directed Medical Research Programs and probably exceeds the total

number of DoD civilians performing medical RDA activities. The biomedical RDA expertise for

vaccines is extremely limited, expensive, and draws largely from academia and industry. The

starting salary for recent college graduates entering the vaccine industry is reported to be in the

range of $40,000 - $50,000 per year. Individuals with sufficient experience to qualify for

process validation positions may start at $100,000 - $120,000 per year. If DoD’s vaccine

requirements were to be met internally, DoD will need to implement compensation policy

changes and provide the resources needed to capture and retain the best talent, with particular

emphasis on manufacturing, testing, clinical trials, and regulatory compliance. The Panel does

not believe that DoD can recruit, retain and manage the skilled personnel needed in advanced

development of vaccines and recommends that development be effected by a combination of

industry and GOCO.

5.1.9 GOCO Facility

In view of the size of DoD’s vaccine program, the limited available industrial vaccine capacity

and the limited industry interest in most DoD vaccines, it is likely that DoD will need to develop

committed vaccine production facilities. The Panel was informed that the DoD has programmed

resources for a proposed GOCO vaccine production facility. The proposed GOCO was viewed

as an essential, partial remedy for DoD. However, it also raised a question about how the

JVAP’s PSC fits with, or would be linked with a GOCO. There was no immediate linkage
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 22

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

defined. With regard to the PSC, the contract base is for three products. All other vaccines are

options under the contract. Currently the three base products on the contract along with two

product options are being developed.

Several of the salient considerations in locating, designing, building, and operating a GOCO

facility to produce vaccines are summarized in Table 15. Programming a vaccine production

facility is considered the easiest part of establishing the overall capability for vaccine

development, manufacturing, and supply. What goes in the facility and how the facility is

managed are considered the most difficult and critical components of the process. It is

important that planned processes drive the design of the facility.

Table 15. Factors in Planning for a GOCO Vaccine Production Facility

 Shell/buildout to process and manufacturing scale

 Expandable

 3 to 4 products/processes capacity

 Pilot production/scale-up

– 2 products at one time

 Inherent clinical, regulatory, QC & QA elements, applied research laboratory capability

 University/industry corridor location is essential − Northeast coast lowest risk

Staffing a GOCO vaccine production facility with the level and depth of expertise needed to

manage and manufacture (process teams) vaccines was thought to be an extremely difficult

challenge for DoD, let alone the vaccine industry. The Panel believes that the DoD must attract,

train, and retain a technically competent cadre of vaccine expertise. In this regard, it is likely

that a greater than normal number of DoD staff will need to fill key positions in the GOCO as a

part of this initiative. The needed expertise is in very short supply and the DoD would have to

compete very aggressively with industry for those limited assets.

With regard to having the right mix and depth of expertise, it is clear that both technical and

management skills are critical to the success of any vaccine R&D program including a GOCO.

Scientific training does not necessarily enhance one’s acquisition management skills and, most

assuredly, acquisition training does not add to one’s scientific acumen. Further, with the

exception of project management skills, the scientific and management skills and experience

needed to operate a successful vaccine program are decidedly different from those needed to run

a weapon systems program. Even within the biomedical disciplines, few are appropriate to

vaccine production. Vaccines (i.e., biologicals) are different from weapon (i.e., hardware)

systems and should not be forced-fit into or equated with such acquisition programs. These

points become critical in terms of staffing and operating a DoD GOCO vaccine facility for

success.

It is also important to keep in mind that project leaders and managers in the biopharmaceutical

industry identify and surface issues immediately upon identification. Success (e.g., cost,

schedule, and performance) is based on timely resolution of problems. Industry’s approach of

having the decision maker on site facilitates this process, as does the culture that rewards the

practice of not hiding risks and technical, process, and regulatory problems. Further, the

constant turnover of DoD Program Managers (PMs) (i.e., continuity of leadership issue) in a
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 23

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

program creates its own impediments to achieving cost, schedule, and performance objectives.

Turnover of PMs may contribute to an environment of deferring problem resolution. In general,

in the vaccine industry, the same team sees a product through the equivalent of DoD’s

development and manufacturing (production) acquisition phases. From the foregoing

perspectives, management (e.g., DoD project management office) of a DoD GOCO vaccine

facility would benefit from alignment with the vaccine industry’s management culture, processes,

and best practices.

Industry does not build a facility for a specific vaccine until clinical trials have proven safety and

proof of concept and process issues have been resolved. When industry builds a new facility,

they plan 3 to 6 years for getting the first vaccine produced and another 12 to 18 months to get

the product licensed. Typically, it costs an additional 20%-30% per year for the first year or two

to get a manufacturing process up and running. Thus, for a $100 million dollar facility, a

manufacturer might expect to expend $20 – $30 million a year to get a process operational

during the first couple of years. During this period, 20%-25% of the product will be discarded

due to product variability. During normal operations, about 5%-10% of the product may be

discarded due to variability from lot to lot. This loss is higher than that experienced (1%-2%) in

the pharmaceutical drug manufacturing process. It is important to realize that discarded product

is lost revenue to the manufacturer. Typical capital investment costs associated with vaccine

facilities are provided in Table 16.

Table 16. Industry Capital Investment and O&M Funding

Benchmark Estimates (8 Product Scale)

 Capital funds >$370M

− ~$300M construction for manufacturing

− ~$70M construction for labs

− ~$75-$115M for each additional vaccine after the initial 3-4

− ~5%-10% infrastructure maintenance/year at year 8

 Operations and Maintenance funds

− ~$300M/year for 8 vaccines

Importantly, the Panel agrees with the concept and scope of the proposed DoD GOCO. In

general, a modular approach (i.e., using identical modules to duplicate a capability as the means

to increase production capacity) is recommended in building a vaccine production facility.

Dedicated manufacturing is preferred to multiple product suites. Ideally, the strategy would

include limiting production−as opposed to development−to one or two (maximum) initial

products. It is extremely important to gain experience and demonstrate success with one product

before taking on others. The level and depth of expertise necessary to achieve success should

not be underestimated. It would be prudent to focus on a single technology, and a related

technology if two products are envisioned at the outset.

Involving the facility and process operators in the design, building, and equipping of a new

facility (e.g., GOCO) is critical to the operational success of any vaccine production venture.

As occurs in industry, infrastructure and modernization must also be integral parts of the budget

supporting any DoD GOCO vaccine production facility. The requirements for sustaining a
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 24

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

vaccine facility infrastructure and facility modifications (e.g., to meet regulatory compliance

requirements) should not be underestimated.

There are a number of risks that must be managed in a DoD GOCO vaccine production facility.

These include factors such as facility design and construction, dedicated versus multi-use

facility, past performance of contractor, technical maturity, process validation, performance

requirement, cost, and schedule. A risk assessment process and plan are needed to effectively

oversee, manage, and mitigate them. A GOCO should only be one part of the DoD strategy for

AVP. However, the Panel considers a GOCO as an essential element in DoD vaccine

procurement.

5.2 Policies

5.2.1 Confidentiality

Industrial vaccine manufacturers hold certain pieces of critical technical and business

information as trade secrets. These secrets largely derive their value from the fact that they are

not known to others who could disclose or use them for their own benefit. Therefore, the holders

of this information are extremely sensitive to the release of this information to any others,

especially if they are unsure whether confidentiality will be maintained. For these reasons

vaccine manufacturers insist that any recipients of confidential trade secret information sign

nondisclosure statements that specifically lay out and create the confidentiality obligations of the

recipients. It is also important to note that any government employee who discloses confidential

information received as part their official duties are subject to criminal prosecution under 18

USC 1905.

5.2.2 Management of BW Perceptions and Treaty Compliance Issues

In addressing DoD vaccine requirements to protect against BW threats, an upfront and agreed

upon public affairs plan is essential in overcoming any negative perceptions (e.g., risk to

population in the area of vaccine production) about DoD’s BDP. Further, the industry does not

want to be wrongly tainted by any suggestion it might be producing BW agents for DoD and it is

opposed to any potential inspections imposed by BW conventions under the pretext that they

might be producing BW agents instead of manufacturing vaccines to protect against such agents.

If such inspections are or will be required, industry would be seriously concerned from both the

perspective of potentially losing proprietary/trade secret manufacturing information, and the

potential perception of being involved in an offensive instead of defensive program. Hence, such

inspection activities would have an adverse impact on the industry’s image and growth and

would not have the support of their shareholders.

5.2.3 Use of Non-U.S. Owned or Based Manufacturers

It is essential that DoD is clear on its position regarding the country of ownership of a vaccine

manufacturer, as well as non-U.S. manufactured vaccines that comply with FDA licensure

requirements. Two of the four major vaccine manufacturers, SmithKline Beecham and Aventis,

are non-U.S. companies. This becomes important in terms of potential implications for DoD

vaccine supplies where a foreign-based owner of a U.S. company may, for whatever reason,
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 25

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

unilaterally end production of DoD’s vaccine. Similarly, political and corporate considerations

could end abruptly DoD’s access to vaccine supplies contracted through non-U.S. based vaccine

manufacturing facilities even if U.S. owned.

5.2.4 User Acceptance of Vaccine

The question of user acceptance of a BDP vaccine was raised, particularly with respect to the

Department’s experience with the anthrax vaccine. The data from longitudinal studies of

vaccines used by the DoD in immunizing its force do not suggest there has been a problem with

regard to adverse events or health care problems. The incidence and type of adverse reactions

(e.g., sore arm or slight swelling at the site of injection) associated with the administration of the

anthrax vaccine appear to have been similar to those experienced with other vaccines. The

primary concern to DoD is not having safe, licensed vaccines to protect its forces from both the

BW and ID threats.

Despite the scientific and health care data that support the fact that there is no unusual risk

associated with the immunization of individuals with the anthrax vaccine, it is felt that gaining

user acceptance could be a potential problem with each BDP vaccine. The public seems to

question the reasonableness of DoD’s mandatory immunization policy for anthrax, and this has

been reflected during Congressional hearings. Further, the public has little basis for appreciating

the impact of infectious disease epidemics on military operations and health care delivery. All

this seems to underscore the importance of having a risk mitigation plan that clearly

communicates to the user (military recipients and commanders at every level), as well as the

public in general, the benefits, immunization rationale, and potential risks of each new vaccine.

It is also important that the DoD establish a policy for when and how all the vaccines in their

portfolio will be administered. Figure 5 summarizes the current vaccines licensed in the U.S.,

including those administered to U.S. Forces. Adding to this list, the vaccines identified as

required for force health protection against BW and endemic disease threats will generate a

seemingly overwhelming number of potential vaccines that might be administered to individual

members of the Armed Forces. Clearly, an immunization policy that stipulates the procedures

(e.g., number of inoculations and routes of administration, and booster requirements) and

phasing of vaccine administration is required.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

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This document reflects the independent opinions of the Vaccine Study Panel

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Current U.S. Licensed Vaccines

Childhood Vaccines Deployment Readiness Additional

• Diphtheria Pertussis Tetanus

• Measles-Mumps-Rubella

• Polio-Salk and Sabin

• Hepatitis B

• H. influenza B

• Pneumococcus

• Varicella

• Hepatitis A

• Cholera

• Japanese encephalitis

• Typhoid

• Yellow Fever

• Influenza

• BCG

• Rabies

Basic-Training Biological Defense

• Meningococcus

• Adenovirus

• Anthrax

• Vaccinia

Figure 5. Current U.S. Licensed Vaccines

5.2.5 Use of IND Vaccines

The DoD has previously relied on using some BDP vaccines under IND status where safety and

efficacy have been established in laboratory models, and safety, but not necessarily efficacy, has

been ascertained in man. The use of such investigational vaccines requires Presidential approval.

This is a difficult issue and one that is fraught with potential problems (e.g., logistical and

political). In overcoming this issue (i.e., perception of a service member as a guinea pig) of

vaccine use under an IND, the DoD must place increased program emphasis on identifying and

demonstrating surrogate markers of immunity (i.e., protection) in man that are acceptable to the

FDA and work with the FDA to achieve sufficient human safety and immunogenicity data, as

well as efficacy data in animal models, to provide licensure of all DoD vaccines.

5.2.6 Vaccine Liability and Indemnification

It is generally true that potential liability is a concern to industry in addressing DoD’s vaccine

needs, particularly as it relates to a product for which efficacy cannot be demonstrated in man;

that is, where surrogate markers and/or surrogate models must be used to provide presumptive

evidence of efficacy; and where there is no way to quantify exposure risk in terms directly

related to a vaccine’s claims of efficacy, as is the case with BW threats. This problem is

associated almost exclusively with the BDP where the BW threat agent is not typically

associated with an endemic disease in a population, as is often the case with those diseases of

concern in the IDP.

Litigation cases involving vaccines, however, have historically been associated with adverse

outcomes, not matters of efficacy. This does not in any way lessen industry’s concerns over

potential litigation where there may be no reasonable way to quantify the risk (e.g., the potential

exposure levels that might be experienced in BW attack) in terms that are directly related to a

vaccine’s claims of efficacy.

Given the experience with BDP immunizations during the Gulf War, there are implications for

policy in terms of removing immunizations from the context of conflict that might also lessen

industry’s concern. The adverse effects of immunizations during basic training and during

mobilization prior to deployment are viewed just as that – adverse reactions. They do not get
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

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This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

complicated by other factors (e.g., stress, exposure to environmental contaminants, and

illnesses).

Since indemnification is available, albeit on a case-by-case basis, it makes sense for companies

to ask and expect to receive it from the government. Indemnification should be a guarantee for

any vaccine manufacturer that is contracted to develop and produce a vaccine to meet DoD’s

unique requirements. Indemnification, limited to that for military use and not commercial sales,

coupled with sound contract provisions, must mitigate industry’s concern in this area.

5.2.7 Vaccine License Holder

Historically, the FDA regulatory process necessitated that the holder of a biological license be

responsible for all submissions to the FDA, manufacturing, clinical trials, and production of the

vaccine. Recent changes in industry practices that are related to the emergence of small

biotechnology companies have led to new FDA guidance for industry and associated cooperative

manufacturing agreements. As a result, a sponsor may now hold a biological license but not

conduct any of the actual steps in the process (e.g., manufacturing and clinical trials).

Although the concept of a virtual company is seen within the pharmaceutical industry, it is

currently viewed as difficult to implement and has not gained widespread support. This

difficulty is due to the intense management and control needed to effectively and efficiently take

a vaccine from discovery to market. A major contributing factor accounting for this difficulty is

the need for integration of multiple, state-of-the-art, developmental research efforts to address

complex scientific issues unique to each vaccine throughout the course of development. The

complexity of the vaccine manufacturing process is also a critical issue. Although there are

validated technological processes for controlling the manufacturing process for a vaccine,

repetition of the process and an element of art in the underlying S&T seem crucial to success.

This problem is evidenced by the vaccine industry’s troublesome experience with replicating the

same product results with the same process in another manufacturing facility or difficulty during

start-up in their own new facilities.

In the absence of the depth of expertise and experience needed to oversee a virtual vaccine

operation and inherent problems with outsourcing aspects of the overall process, such operations

have enormous attendant risks for failure. The risks to DoD in not holding the biological license

for a product are probably minimal except in the case where it may become necessary to have

another manufacturer produce the vaccine. It is felt that well thought out and tight contract

provisions, along with enforcement, could largely mitigate the risk associated with this single

exception.

6.0 FINDINGS AND RECOMMENDATIONS

DoD must adopt industry practices, capture industry interest, and invest its own corporate

resources in the management and execution of the AVP program if it has any hope of solving its

vaccine requirements. This may well require changes in DoD policy and organization,

legislation, and statutory commitments. The issues of U.S. national preparedness and the

potential use of DoD vaccine stockpiles to meet national needs were discussed; however, it was
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

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This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

not considered to be within the scope of the Panel’s charge to include this in the overall

recommendations for DoD’s AVP. Nevertheless, the Panel hoped that its recommendations and

DoD’s planning tools would have practical utility and application to other agencies involved

with national preparedness.

A combination of industry, government, and an integrated approach from discovery through

production and sustainment are essential to the success of DoD’s vaccine programs. The critical

elements of a combined integrated approach to DoD’s AVP strategy are summarized in Table 17.

Table 17. Elements of a Combined Integrated Approach to DoD AVP

 Management/development skills of industry

 Acquisition skills of DoD

 Scientists from Federal, academic/industry labs

 Exploit industry development/manufacture where possible

 GOCO for development/manufacture of remaining products

This strategy should include the vaccine industry’s involvement as well as that of DoD and other

government agencies. It is also important not to inadvertently lose any capability in the process

of implementing any new vaccine acquisition strategy. A balanced strategy is quintessential to

success and should include a multipronged approach. The Panel’s goal in recommending the

following management structure was to make it consistent with current DoD acquisition

management structure, (but lean and responsive!) and to invest management with the strong

technical expertise and advice essential for success in vaccine development. The Panel considers

that the principal weaknesses of the current DoD AVP program are the current diffuse

management structure and the lack of technical expertise in management beyond the S&T phase.

Specific recommendations include:

• Mainstream BDP and IDP vaccine programs as integrated ACAT I programs to ensure

visibility, competitiveness with other programs, and that warfighter needs are satisfied in a

timely manner (Table 18).

Table 18. Industry-Based Management Model for DoD AVP

 Tailored Acquisition Model

– OSD VAE

– Oversight (ACAT I)—technically qualified

– Strategic Vaccine Board advises VAE

 Vaccine Acquisition Review Council (VARC) and Defense Medical

Requirements Council (DMRC)

 Joint Program Executive Officer (PEO)

– VAE and PEO with scientific and acquisition skills
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

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This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

• Implement an organizational alignment that mirrors the vaccine industry’s short chain of

command and decision making at the level of the project manager, with requisite technical

expertise in the chain of command, project management, and execution level (Figure 6).

Figure 6. Industry-Based Management Organization for DoD AVP

• Establish a Vaccine Acquisition Executive (VAE) as full life-cycle advocate for all DoD

vaccine programs (Table 18, Figure 6).

• Establish a Strategic Board to review the DoD AVP and advise the VAE (Table 18, Figure

6). This Strategic Board staff consists of industry executives and health care professionals

having a working expertise in clinical infectious diseases, international health, or vaccine

research, development, clinical testing, operations and quality systems. It should review

programs strategically at least twice a year.

• Establish a VARC to advise and support milestone decisions by the VAE (Table 18, Figure

6). Members of the VARC should mirror for DoD the capabilities, experience, and technical

skills of the Strategic Board; however, the VARC must be empowered to perform inherently

government functions.

• Charter a technically qualified Joint PEO for the AVP program that is accountable to the

VAE (Table 18, Figure 6). The PEO must have authority over the entire vaccine life cycle

from discovery through post-licensure activities.

• Establish a Technical Board to review the DoD AVP program that meets quarterly and advise

the PEO. This technical board staff consists of working experts with tactical “hands on”

experience in the major elements of vaccine development−discovery, manufacturing, clinical

development, regulatory affairs, quality control and assurance, and assay development. It

would principally be derived from industry and would meet quarterly to review tactical plans

and progress of the program (including the GOCO) and advise the PEO.

• Adopt an industry-based management philosophy for DoD AVP (Table 19).

PM PM

Strategic Board VARC DMRC

Technical Board

Performers Labs GOCO

PM

Industry

Universities

USD(AT&L)

PEO

VAE
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

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This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Table 19. Industry-Based Management Philosophy for DoD AVP

 Scientific & technical advisors on tactical operations to PEO

– Periodic (scheduled) review

– All process/product candidates

– Pharmaceutical executives

– Senior scientists/physicians

 Breaches in approved program baseline reviewed by VAE

 PEO responsible for sponsoring ($) S&T/relevant infrastructure and

exploits DoD laboratory capability

 No dual hats

• Adopt a tailored life-cycle management model that mirrors that used by the vaccine industry

wherein decisions to transition candidates from discovery (S&T) to development and

manufacturing only occur when risks have been reduced to an acceptable level [e.g., after

Phase 2 clinical trials and development and manufacturing schedules allow for completion

within 3 to 6 years].

• Estimating that 8 DoD vaccines would reach licensure in 7 to 12 years, the estimated cost of

the AVP program is $3.2 billion.

• Develop a sound investment strategy for the DoD AVP portfolio (Tables 13 and 14). A

major initial goal of the VAE and PEO should be review of the entire AVP program vaccine

candidates for feasibility and status in the vaccine life cycle.

• Use an integrated strategy that includes; GOCO (see Tables 15 and 16), PSC, DoD

biomedical laboratories, and DoD partnerships with commercial companies (including

appropriate incentives), National Institutes of Health, Public Health Service, and academia.

• Develop an integrated plan, including checks and balances (i.e., QA and QC) for managing

the functions and responsibilities associated with the contracts, administration, operation and

long-term sustainment of the DoD vaccine program (e.g., partnerships with industry and

academia, GOCO vaccine facility, PSC, DoD biomedical laboratories, as well as oversight

and management staffs).

• Promote a robust S&T strategic plan with increased emphasis on surrogate markers of

immunity (protection) in man.

• Exploit special contract provisions, as well as Other Transaction Authority (OTA), that allow

maximum flexibility in meeting vaccine program needs, and special incentives for success.

• Establish a unified process for identifying and prioritizing threats and requirements.

• Establish AVP plans

− Core personnel incentive, recruitment, retention, and staffing plan (Table 6)

− Facility infrastructure sustainment and modernization plan

− Surge capacity plans (including conversion of existing plants)

− Strategic inventory plan

− Contract management plan with assistance from Defense Contract Management

Agency

− National public affairs plan that informs the public of DoD’s vaccine plan, including

rationale and benefits (e.g., combat capability, readiness, deterrence, and national

preparedness).
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

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This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Finally, the current DoD AVP program has extremely limited input from the vaccine industry.

Therefore, the major source of invaluable expertise and experience is missing from the Program.

The Panel recommends that DoD, at a very senior level, meet with the Chief of Executive

Officers or Chief Operating Officers of the principal vaccine manufacturers. (This could be done

through the Pharmaceutical Research and Manufacturers Association and BIO). The agenda

should be:

• Outline the threat and requirements of the DoD program.

• Seek advice as to whether industry would contribute to development of all required DoD

vaccines or to selected DoD vaccines.

• Seek support for the GOCO strategy to develop vaccines of limited interest to industry.

• Seek industry participation as advisors on the strategic advisory board to the VAE and on the

technical advisory board to the PEO.

The Panel is confident that such high-level exposure to the DoD AVP program will enhance the

possibility of industry involvement in development of certain DoD vaccines and at the very least,

obtain industry support for the DoD program and GOCO and for the availability of

pharmaceutical executives and industry vaccine development personnel to serve as critical

advisors to the program.

The Panel’s findings and recommendations are presented below so as to respond to the four

specific areas of focus that the DEPSECDEF requested the independent panel of experts to

address. A summary of findings and recommendations for each of the DEPSECDEF focus areas

is provided in Table 20.
DoD Acquisition of Vaccine Production Report to the De

by the Inde

1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Table 20. Summary of Findings and Recommendations by DEPSECDEF Focus Area

Focus Area Findings Recomm

1 - Vaccines to protect Service members

against BW threats as well asinfectious diseases.

Vaccines for BW defense and protectionagainst endemic diseases are essentialenablers of force projection.

Combine programs from d

2 - A comparison of current Department

efforts with best business practices inthe biologics industry, and if/how theDepartment can leverage the bestaspects of the private sector programsfrom industry.

Current Department efforts do not meetindustry best practices: Diffuse management and fragmented

lines of responsibility

 Inadequate scientific oversight Inadequate program integration from

discovery through licensure

 Inadequate resources to meet goals

Adopt integrated approach  Management and devel Accountable, lean DoD  Strong technical guidan GOCO

3 - A determination of whether the DoD

program requires acquisition processesunique from normal departmentalacquisition procedures.

Vaccine acquisition processes are different

from weapons system acquisitionprocesses and success requires differentprocedures.

 Strong technical input 

− Workforce− Management

 Stable, long-range fund Reprogramming author

4 - The development of recommendations

for how the Department should bestdevelop and oversee a vaccineacquisition production program.

DoD AVP management practices aregenerally contrary to industry bestpractices.

 Combined, integrated in Focused and streamline Segregated, OSD-spons Incentivized industry in DoD, Executive Branch

support to remove impenecessary incentives
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

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This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

A-1

APPENDIX A

Conduct of the Study of Department of Defense Acquisition of Vaccine Production

By memorandum dated July 20, 2000 (Attachment I) the Deputy Secretary of Defense directed

the Director, Defense Research and Engineering (DDR&E) and the Assistant Secretary of

Defense (Health Affairs) [ASD(HA)] to “...jointly contract with a private organization or panel

of experts to conduct a comprehensive study of the Department of Defense’s (DoD’s)

procurement of vaccine production. The experts involved in the study should have expertise in

the scientific, regulatory and industrial aspects of vaccine production. The study should focus on

review of the following areas:

a. Vaccines to protect Service members against biological warfare threats as well as

infectious diseases.

b. A comparison of current Department efforts with best business practices in the

biologics industry, and if/how the Department can leverage the best aspects of the

private sector programs from industry.

c. A determination whether the DoD program requires acquisition processes unique

from normal departmental acquisition procedures.

d. The development of recommendations for how the Department should best develop

and oversee a vaccine production program.”

The DDR&E was directed to fund this study and the Director, Bio Systems, Office of the DUSD

(S&T), ODDR&E, assigned the study support task to Science Applications International

Corporation (SAIC) using an existing delivery order under SAIC contract N00600-96-D-2109.

At that time the DoD was sponsoring or conducting a number of other assessments related to

vaccines for force protection. These included:

a. Defense Science Board Summer Study 2000, Task Force on Defense against

Biological Weapons that considered the vaccine supply chain for Defense needs.

b. Assessment by the Principal Deputy Under Secretary of Defense for Acquisition,

Technology and Logistics [PDUSD(AT&L)] of BioPort Corporation production of

the Food and Drug Administration (FDA) licensed, anthrax vaccine adsorbed.

c. A cost and operational analysis of a government-owned and contractor-operated

(GOCO) vaccine production facility for biological defense vaccines sponsored by the

Deputy Assistant to the Secretary of Defense (Chemical/Biological Defense

[DATSD(CBD)] through the Joint Program Office for Biological Defense (JPO BD)

and executed by the Joint Vaccine Acquisition Program, Project Management Office

(JVAP PMO).
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A-2

d. An assessment of the Military Infectious Diseases Research Programs (MIDRP) by

the National Academy of Sciences, Institute of Medicine (IOM) for the Commanding

General, U.S. Army Medical Research and Materiel Command (USAMRMC) who

executes the Secretary of the Army lead agent responsibility for the military

infectious diseases research, development, test and evaluation programs.

Supported by SAIC, the DATSD(CBD) and Director, Bio Systems recommended a Panel

(Attachment II with resumes at Attachment III) and study plan to the DDR&E and ASD(HA).

These were approved by memorandum on August 17, 2000 signed by the DDR&E and

ASD(HA) (Attachment IV). This memorandum jointly requested Defense Components involved

in AVP to provide briefings and narrative back-up concerning the topic. The approach the Panel

Chair approved was for SAIC staff to review and critique the briefings with the intent to both

highlight information for the Panel members’ consideration and to identify areas that might

require clarification for elaboration in follow-on presentations by Defense Component personnel.

SAIC also established a secure web site for Panel members to access DoD Directives,

Instructions, and related information concerning DoD acquisition of vaccine procurement.

Throughout their deliberations the Panel was supported by the DATSD(CBD), Director, Bio

Systems, and SAIC staff who provided information and assisted the Panel members’

understanding of DoD organizations, practices and procedures. It should be understood that the

Panel Chair was fully responsible for and directed this effort. DoD and SAIC staff provided

support and assistance as requested.

The first meeting of the Panel was held September 25 and 26, 2000 (Attachment V). During this

meeting the Panel received the Formal Charge from Dr. Mark, DDR&E and Dr. Clinton,

ASD(HA) who also discussed background information and their perspectives on the problem

with Panel members. During this meeting, SAIC staff presented and supported Panel discussions

of briefings received in response to the DDR&E and ASD(HA) request, as well as related

background information such as FDA regulatory considerations that directly influence the

problem, Defense Acquisition Workforce reform initiatives, and DoD-specific regulatory

considerations. Additionally, Mr. Steve McManus provided a briefing on vaccine management

by the Defense Support Center Philadelphia, Defense Logistics Agency (DLA). Copies of all

presentations are included in Volume II of this report.

The Panel Chair determined that the next step was for the Panel members to conduct interviews

with specific DoD personnel involved in Defense AVP. These interviews were conducted during

the second meeting conducted October 11, 12 and 13, 2000 (Attachment VI). The morning of

the first day focused on Defense procurement with a briefing by the Director, Defense Contract

Management Agency followed by a discussion of procurement and contracting support to

GOCOs in general and related matters led by Mr. Robert Scott, past Deputy Director, DLA. The

second day focused on Defense acquisition practices and procedures and DoD research,

development and acquisition matters as they relate to vaccines. The Panel interviewed the

following individuals on the second day:

• Lieutenant General Paul Kern, U.S. Army, Military Deputy to the Assistant Secretary of

the Army (Acquisition, Logistics and Technology) [ASA(ALT)] and Director, Army

Acquisition Career Management.
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by the Independent Panel of Experts

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• Major General John Parker, M.D., U.S. Army, Deputy for Medical Systems,

OASA(ALT) and Commanding General, USAMRMC.

• Mrs. Vicky Armbruster, Joint Program Manager for Biological Defense.

• Colonel Charles Hoke, M.D., U.S. Army, Director, MIDRP, Headquarters, USAMRMC.

• Colonel David Danley, Ph.D., U.S. Army, Project Manager, JVAP.

Throughout the second (October 11-13, 2000) and third meeting (November 8 and 9, 2000), the

Panel members assessed Defense efforts and acquisition processes against industry best

practices. These assessments largely drew on the Panel members’ expert opinion and experience

of what does and does not work in the private sector. Within the industry considerations,

distinctions were made between the large vaccine manufactures and smaller biotechnology firms

and how their practices contrasted and compared with the DoD efforts. These assessments

served as the basis for recommendations that were initiated during the second meeting and

concluded during the third meeting.
INTENTIONALLY BLANK.
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and should not be construed as the official position of the DoD.

ATTACHMENT I

Review of the Department’s Acquisition of Vaccine Production Memorandum
INTENTIONALLY BLANK.

INTENTIONALLY BLANK.
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ATTACHMENT II

Deputy Secretary of Defense’s Independent Panel of Experts

Acquisition of Vaccine Production
INTENTIONALLY BLANK.
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by the Independent Panel of Experts

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1

Franklin H. Top, Jr., M.D.—Panel Chair

Executive Vice President and Medical Director

MedImmune, Inc.

35 West Watkins Mill Road

Gaithersburg, MD 20878

topf@medimmune.com

Phone: 301-527-4251

Fax: 301-527-4201

John J. Dingerdissen

Senior Director, Viral Vaccine Manufacturing

Merck Manufacturing Division

Merck & Co., Inc.

P.O. Box 4, WP28-79

West Point, PA 19486-0004

john_dingerdissen@merck.com

Phone: 215-652-4460

Fax: 215-652-4775

William H. Habig, Ph.D.

Director

R&D Quality Assurance and Compliance

Centocor, Inc.

200 Great Valley Parkway

Malvern, PA 19355-1307

Phone: 610 889-4405

Email: Habigw@Centocor.com

Gerald V. Quinnan, Jr., M.D.

Professor

Preventive Medicine, Medicine, and Microbiology

Uniformed Services University of the Health Sciences

4301 Jones Bridge Road

Bethesda, MD 20814

Phone: 301-295-3734

Fax: 301-295-1971

Email: gquinnan@usuhs.mil
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

2

Rita L. Wells, Ph.D.

Deputy Executive Director

Committee for Purchase from People

 Who are Blind or Severely Disabled

1421 Jefferson Davis Highway

Jefferson Plaza 2, Suite 10800

Arlington, VA 22202-3259

Phone: 703-603-0657

Fax: 703-603-0655

Email: rwells@jwod.gov

Technical Advisors − Government

Primary:

Anna Johnson-Winegar, Ph.D.

Deputy Assistant to the Secretary of Defense for Chemical/Biological Defense

Programs

3050 Defense Pentagon, Room 3C257

Washington DC 20301-3050

Phone: 703-693-9410

Fax: 703-695-0476

Email: johnsoad@acq.osd.mil

Robert E. Foster, Ph.D.

Director, Bio Systems

Office of the Deputy Under Secretary of Defense (Science and Technology)

3080 Defense Pentagon, Room 3D129

Washington, DC 20301-3080

Phone: 703-697-8714

Fax: 703-693-7042

Email: fosterre@acq.osd.mil

Other:

Steve McManus

Director, Pharmaceuticals Group

Defense Supply Center, Philadelphia

Defense Logistics Agency

DSCP-MG (Bldg 6A)

700 Robbins Avenue

Philadelphia, PA 19111

Phone: 215-737-2801

Email: smcmanus@dscp.dla.mil
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

3

Thomas C. Fileccia 

Branch Chief,

Depot, Managed Care, Direct Vendor Delivery Sections

Defense Supply Center, Philadelphia

Medical Directorate (DSCP-MG)

700 Robbins Avenue

Philadelphia, PA 19111-5092

Phone: 215-737-2839

Fax: 215-737-3127

Email: tfileccia@dscp.dla.mil

Technical Advisors/Analysts – Contract

Daniel L. Rickett, Ph.D. – Lead Analyst

Vice President and Manager

Biomedical Technology Division

Science Applications International Corporation

William H. Bancroft, M.D.

Senior Medical Scientist

Biomedical Technology Division

Science Applications International Corporation

Donna L. Bareis, Ph.D.

Corporate Vice President and Deputy Group Manager

Biomedical Sciences Group

Science Applications International Corporation

Mark R. Brunswick, Ph.D.

Expert Biologist/Senior Regulatory Scientist

Biomedical Technology Division

Science Applications International Corporation

Joseph C. Denniston, V.M.D., Ph.D.

Senior Biomedical Scientist

Biomedical Technology Division

Science Applications International Corporation

Thurman D. Gardner, C.C.E/A.

Medical Acquisition Analyst

Science Applications International Corporation
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

4

James M. Miller, Esq.

Senior Program/Policy Analyst

Science Applications International Corporation

George T. Singley, III

President, Hicks Associates, Inc.

1710 SAIC Drive

P.O. Box 1303

Mail Stop: 1-13-7

McLean, VA 22102

Phone: 703-676-5958

Fax: 703-676-5813

Email: george.t.singley.iii@saic.com

Joseph F. Soukup, Ph.D.

Group Senior Vice President and Manager

Biomedical Sciences Group

Science Applications International Corporation

Phone: 703 744-7500

Fax: 703 288-5404

Email: Joseph.F.Soukup@saic.com
1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

ATTACHMENT III

Panel Member Resumes
INTENTIONALLY BLANK.
CURRICULUM VITAE

Franklin H. Top, Jr., M.D.

EDUCATION

University of Minnesota, Pediatric Infectious Disease Fellowship, 1964 -1966

University of Minnesota, Pediatric Residency, 1962 - 1964

University of Minnesota, Pediatric Internship, 1961 - 1962

Yale University, M.D. cum laude, 1961

Yale University, B.S. in Biochemistry, 1957

PROFESSIONAL EXPERIENCE

MEDIMMUNE, INC.

1988 - Present

Executive Vice President, Medical Director, and Director

Responsible for planning and execution of clinical studies of MedImmune products. Member,

Board of Directors.

PRAXIS BIOLOGICS

1987 - 1988

Senior Vice President, Clinical Research and Medical and Regulatory Affairs

Responsible for planning and execution of all clinical research involving Praxis’ vaccines.

Responsible for medical affairs and for corporate liaison with the FDA, Center for Biological

Evaluation and Research . As additional duty, served as Executive Vice President and acting

Chief Executive Office of the company.

WALTER REED ARMY INSTITUTE OF RESEARCH

1983 - 1987

Director and Commandant

Commander and scientific leader of the Department of Defense’s largest medical research

laboratory (and five overseas satellite laboratories) with research interests in infectious diseases,

drug and vaccine development, military occupational health hazards, military stress and

neuropsychiatry. Responsible for staff of over 1,000 employees and an annual budget of $45

million.

UNITED STATES ARMY MEDICAL RESEARCH

INSTITUTE OF CHEMICAL DEFENSE

1981 - 1983

Commander

Commander and scientific leader of the Army’s lead laboratory for medical defense against

chemical warfare. Developed and implemented new programs in drug development. Responsible

for a staff of 200 people, an annual budget of $13 million, and $20 million contract program.
Franklin H. Top, Jr., M.D. - Page 2

WALTER REED ARMY INSTITUTE OF RESEARCH

1979 - 1981

Deputy Director

Responsible for daily operations of the Department of Defense’s largest medical research

laboratory.

UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES

1978 - 1987

Professor of Pediatrics

Participated in Pediatric Infectious Diseases rounds, conferences, and attended on Pediatric

Infectious Disease service at Walter Reed Army Medical Center.

WALTER REED ARMY INSTITUTE OF RESEARCH

1976 - 1978

Director, Division of Communicable Diseases and Immunology

Directed and supervised all Walter Reed Army Institute of Research research on vaccines and

infectious diseases.

1973 - 1976

Chief, Department of Virus Diseases

Directed and supervised a virus laboratory of 40 employees with research interests in viral

respiratory diseases, dengue virus and hepatitis virus. Served as Department of Defense working

liaison with other federal agencies - Center for Disease Control, National Institute of Allergy and

Infectious Diseases, and the Bureau of Biologics, Food and Drug Administration - in the National

Influenza Vaccine Program.

SOUTHEAST ASIA TREATY ORGANIZATION

MEDICAL RESEARCH LABORATORY

1970 - 1973

Chief, Department of Virology

Directed and supervised a virus research laboratory with 40 employees. Coordinated WHO

sponsored studies of the immunopathogenesis of dengue hemorrhagic fever with Scripp’s Clinic

and Research Foundation, Ramathibodi Medical School, and various other hospitals. Supervised

the training of the Army’s Pediatric Infectious Disease fellows tour at Bangkok Children’s

Hospital.

WALTER REED ARMY INSTITUTE OF RESEARCH

1966 - 1970

Assistant Chief, Department of Virus Diseases

Internist, Department of Virus Diseases

Internist then Assistant Chief, Department of Virus Diseases. Designed and conducted clinical

studies of safety and immunogenicity and later efficacy trials of live oral adenovirus type 4 and 7

vaccines for prevention of Acute Respiratory Disease in military recruits.
Franklin H. Top, Jr., M.D. - Page 3

MEMBERSHIPS

Alpha Omega Alpha Medical Honor Society, 1960

American Academy of Pediatrics, Fellow

American Medical Association

American Association for the Advancement of Science

American Association of Immunologists

American Board of Pediatrics, 1966

Society for Pediatric Research

American Society of Tropical Medicine and Hygiene

Infectious Disease Society of America

Microbial & Infectious Disease Advisory Committee, National Institute of

 Allergy and Infectious Diseases, NIH, 1976 - 1980

HONORS

Colonel, U.S. Army (retired)

Legion of Merit with Two Oak Leaf Clusters

Meritorious Service Medal

SELECTED PUBLICATIONS

1. The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus

monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in

high-risk infants. Pediatrics, in press.

2. The PREVENT Study Group. Reduction of RSV hospitalization among premature

infants and infants with bronchopulmonary dysplasia using Respiratory Syncytial Virus

Immune Globulin. Pediatrics, 99: 93-99, 1997.

3. Bancroft, W.H., Top, F.H. Jr., Eckels, K.H., Anderson, J.H. Jr., McCown, J.M. and

Russell, P.K. Dengue-2 vaccine: Virological, immunological and clinical responses of six

yellow fever-immune recipients. Inf & Immun 31: 698-703, 1981.

4. Takafuji, E.T., Gaydos, J.C., Allen, R.G. and Top, F.H. Jr. Simultaneous administration

of live enteric-coated adenovirus types 4, 7 and 21 vaccines; Safety and Immunogenicity.

J Inf Dis 140: 48-53, 1979.

5. Wise, T.G., Dolin, R., Mazur, M.H., Top, F.H. Jr., Edelman, R. and Ennis, F.A.

Serological responses and systemic reactions in adults following vaccination with

bivalent A/Victoria-A/New Jersey and monovalent B/Hong Kong influenza vaccines. J

Inf Dis 136: S507-S517, 1977.

6. Top, F.H. Jr., and Russell, P.K. Influenza A/Swine at Fort Dix, New Jersey (JanuaryFebruary 1976). IV. Summary and speculation. J Inf Dis 136: S376-S380, 1977.
Franklin H. Top, Jr., M.D. - Page 4

7. Hodder, R.A., Gaydos, J.C., Allen, R.G., Top, F.H. Jr., Nowosiwksy, T. and Russell, P.K.

Influenza A/Swine at Fort Dix, New Jersey (January-February 1976). III. Extent of spread

and duration of the outbreak. J Inf Dis 136: S363-S368, 1977.

8. Gaydos, J.C., Hodder, R.A., Top, F.H. Jr., Allen, R.G., Soden, V.J., Nowosiwsky, T. and

Russell, P.K. Influenza A/Swine at Fort Dix, New Jersey (January-February 1976). II.

Transmission and morbidity in units of cases. J Inf Dis 136: S363-S368, 1977.

9. Gaydos, J.C., Hodder, R.A., Top, F.H. Jr., Soden, V.J., Allen, R.G., Bartley, J.D., Zabkar,

J.H., Nowosiwsky, T. and Russell, P.K. Influenza A/Swine at Fort Dix, New Jersey

(January -February 1976). I. Case finding and clinical study of cases. J Inf Dis 136: S356-

362, 1977.

10. Parkman, P.D., Galasso, G.J., Top, F.H. Jr. and Noble, G.R. Summary of clinical trials of

influenza vaccines. J Inf Dis 134: 100-107, 1976.

11. Benenson, M.W., Top, F.H. Jr., Gresso, W., Ames, C.W. and Altstatt, L.B. The virulence

to humans of Japanese encephalitis virus in Thailand. Am J Trop Med Hyg 24: 974-980,

1975.

12. Top, F.H. Jr. Control of adenovirus acute respiratory disease in U.S. Army trainees. Yale

J Biol Med 48: 185-195, 1975.

13. Bokisch, V.A., Top, F.H. Jr., Russell, P.K., Dixon, F.J. and Muller-Eberhard, H.J. The

potential pathogenetic role of complement in dengue hemorrhagic shock syndrome.

NEJM 289: 996-1001, 1973.

14. Pathogenetic mechanisms in dengue hemorrhagic fever: Report of an international

collaborative study. Bull. WHO 48: 117-133, 1973.

15. Dudding, B.A., Top, F.H. Jr. , Scott, R.M., Russell, P.K. and Buescher, E.L. An analysis

of hospitalizations for acute respiratory disease in recruits immunized with adenovirus

type 4 and 7 vaccines. Am J Epidem 95: 140-147, 1972.

16. Top, F.H. Jr., Dudding, B.A., Russell, P.K. and Buescher, E.L. Control of respiratory

disease in recruits with type 4 and 7 adenovirus vaccines. Am J Epid 94: 142-146, 1971.

17. Top, F.H. Jr., Buescher, E.L., Bancroft, W.H. and Russell, P.K. Immunization with live

types 7 and 4 adenovirus vaccines: II. Antibody response and protective effect against

acute respiratory disease due to adenovirus Type 7. J Inf Dis 124: 155-160, 1971.

18. Top, F.H. Jr., Grossman, R.A., Bartelloni, P.J., Segal, H.G., Dudding, B.A., Russell, P.K.,

and Buescher, E.L. Immunization by selective intestinal infection with adenovirus type 7:

Tests for safety, infectivity, antigenicity and potency in volunteers. J Inf Dis 124: 239-

248, 1970.
Franklin H. Top, Jr., M.D. - Page 5

19. Top, F.H. Jr. and Wannamaker, L.W. The serum opacity reaction of Streptococcus

pyogenes: The demonstration of multiple, strain-specific lipoproteinase antigens. J Exp

Med 127: 1013-1034, 1968.

20. Top, F.H. Jr., Wannamaker, L.W., Maxted, W.R. and Anthony, B.F. M antigens among

group A streptococci isolated from skin lesions. J Exp Med 126: 667-635, 1967.
INTENTIONALLY BLANK.
JOHN J. DINGERDISSEN

825 Bainbridge Drive

West Chester, PA 19382

(215) 652-4460 (W) (610) 399-3772 (H)

PERSONAL HISTORY

Birth Date: November 10, 1949

Citizenship: USA

Marital Status: Married, three children

PROFESSIONAL EXPERIENCE

Merck Manufacturing Division

Viral Vaccine Manufacturing, Senior Director: 1997-Present

• Responsible for a staff of ~45 professionals and ~160 union employees involved in the manufacture of

Varivax®, M-M-R® II, Vaqta®.

• Responsible for the strategic capacity planning for the Poultry Area, Rotavirus and Varivax®.

• Responsible for the start-up of the new Rotavirus manufacturing facility.

• Responsible for Vaccine Operations’ representation on the Company negotiation committee with the PACE

union.

• Directs the organization in establishing production, cGMP, safety and environmental initiatives.

• Responsible for a budget of ~$40 MM, producing ~$600 MM worth of bulk vaccine product.

Merck Manufacturing Division

Biological Manufacturing, Senior Director: 1994-1997

• Responsible for a staff of ~75 professionals and 250 union employees involved in the manufacture of M-M-R

II, RECOMBIVAX HB, Elspar, Varivax and Vaqta.

• Responsible for the supply of launch materials for three new products: Varivax, Vaqta and COMVAX®.

• Responsible for Vaccine Operations’ representation on the Company negotiation committee with the OCAW

union.

• Responsible as point person for all major labor relations issues.

• Directs the organization in establishing production, cGMP, safety and environmental initiatives.

• Responsible for a budget of ~$40-50 MM.

Merck Manufacturing Division

Biotechnology, Director: 1990-1994

• Responsible for the Biological Technical Services and Biological Process Engineering departments. The focus

of these groups is to provide for technical implementation of new processes as well as process improvement and

technology enhancement in Biological Manufacturing. In addition, a third area of responsibility includes the

design and implementation of the Biotechnology Manufacturing Complex, a $170 MM production facility.
John J. Dingerdissen Page 2

• Direct the development and organization of ~50 staff scientists including cell biologists, microbiologists,

virologists, biochemists, chemical engineers, biochemical engineers, and mechanical engineers.

• Manage a $5.5+ MM budget.

• Direct the strategic objectives for the Biotechnology organization. Develop and lead the implementation of the

vision for the Biotechnology area.

• Establish the objectives, productivity initiatives, and direction for each of the technical departments.

• Direct the cohesive partnership with Merck Research Laboratories on the process optimization and

implementation of new products and processes.

• Responsible for creating an environment of risk-taking and empowerment to help the scientists/engineers to

solve taxing and extremely difficult technical production problems.

E. I. DuPont de Nemours & Company

Biotechnology Development Group, Senior Research Supervisor: 1988-1990

• Responsible for the fermentation/Protein Purification Process Development, GMP Scale-Up groups and the

Analytical and Fermentation research support groups. Group included 32 scientists and support personnel.

• Chaired the 1L-1 Development Subcommittee.

• Primary responsibility for the preparation of recombinant proteins and polypeptides to support all phases of

clinical development through product licensing for therapeutic and diagnostic business groups.

• Responsible for the production for bulk antigen for support of commercial European sales of an AIDS test kit.

• Responsible for the development of a raw materials management system for the production of GMP clinical

supplies.

• Responsible for the process development and production of multigram quantities of PAI for research studies in

animals.

• Managed the development and supervision of 3 Ph.D. scientists, 5 M.S./B.S. scientists, and 24 B.S. technicians.

• Responsible for the development of state-of-the-art capability in cell harvesting using UF.

SmithKline & French Laboratories

Biopharmaceutical R&D

Scientific Coordination Biotechnology Research, Senior Investigator: 1987-1988

• Coordinate and facilitate scientific and technical aspects of research programs and feasibility studies in

Biopharmaceutical R&D.

• Reporting directly to the V.P. of Biopharmaceutical R&D, manage interactions and serve as scientific liaison

between Biopharmaceutical R&D and other areas of SK&F and SKB regarding coordination of research efforts.

• Coordinate AIDS diagnostic and vaccine development programs in collaboration with SK-Bioscience and SKBiologicals.

• Associate Project Leader for the Malaria Vaccine Development Project.
John J. Dingerdissen Page 3

• Scientific Program Coordinator for the AIDS Antiviral Research Program and the Third Generation

Fibrinolytics Research Program.

• Coordinate and facilitate research efforts in collaboration with outside academic and industrial partners.

• Recommend priorities for research programs and feasibility studies within Biopharmaceutical R&D.

• Represent V.P. of Biopharmaceutical R&D on safety, facilities, and GMP committees internally and I.B.A. and

P.M.A. committees externally.

SmithKline & French Laboratories

Protein Biochemistry/Natural Products

Pharmacology Depts., Associate Investigator: 1984-1986

• Completed formal management training at the Wharton School of Business, University of Pennsylvania.

• Implemented the use of Project Scheduling Network software for planning clinical production campaigns.

• Responsible for the institution of GMP procedures and compliance testing for large scale protein purification.

• Interacted with appropriate scientists (molecular genetics, fermentation, cell culture, and pharmaceutics) and

support functions (site services, regulatory compliance, engineering, etc.) in order to assure quality of clinical

batches.

• Responsible for the supervision of the isolation/purification of clinical supplies of protein from rDNA sources.

• Responsible for writing the Manufacturing Control Instructions and Standard Operating Procedures according to

GLP/GMP guidelines.

• Contributed to the design and completion of the purification scheme used to produce 75 grams of tissue

plasminogen activator for pre-clinical Path/Tox studies, Phase I and II clinical trials.

• Responsible for the development of a raw materials management system for GMP production supplies.

• Assumed a major role in the successful completion of the preparation of two bulk malaria vaccines for clinical

trials by planning and directing the actual process runs.

• Contributed to the preparation of three INDs.

• Increased the scientific capability of the group with personnel changes and equipment acquisitions.

• Proposed and implemented the acquisitions of high-tech robotics equipment for automation of tedious assays.

• Contributed to the design and completion of the purification scheme used in the production of Hepatitis B

antigen and malaria antigen.

• Developed new rapid approaches to antibiotic discrimination.

• Participated on the R&D Chemical Health and Safety Committee as a member representing the Vice President

of Biological R&D.

• Contributed to the design of the downstream protein purification facility in a Biopharmaceutical GMP Pilot

Plant.

SmithKline & French Laboratories

Natural Products Pharmacology Dept., Senior Scientist: 1982-1983
John J. Dingerdissen Page 4

• Assumed responsibility for the Recovery Group in Natural Products Pharmacology.

• Responsibilities included planning, scheduling, and reporting all experiments: interacted with four research

program heads in the establishment and completion of objectives; supervision of five technicians; chairman of

the Lead Evaluation Subcommittee.

• Designed the downstream processing facilities in a temporary pilot plant.

• Member of the Career Development Study Group.

• Developed straight forward approaches to antibiotic discrimination with a technological breakthrough.

• Introduced HPLC technology into the research group.

• Implemented the use of a computer data file for research data.

SmithKline & French Laboratories

Medicinal Chemistry Dept., Senior Medicinal Chemist: 1980-1982

• Responsible for the planning and scheduling of research in the antibiotic recovery area.

• Developed new techniques to aid in t he early research stages of current AHP development project.

• Managed the development and supervision of 25 technicians/associates.

SmithKline & French Laboratories

Medicinal Chemistry Dept., Medicinal Chemist: 1977-1980

• Responsible for research in antibiotic discovery, purification and structure determination.

• Developed mini-resin screen for methods development: saves time and money.

• Supervision and development of two technicians.

SmithKline & French Laboratories

Medicinal Chemistry Dept., Associate Medicinal Chemist: 1973-1977

• Responsible for research in antibiotic discovery, purification and structure determination.

Purdue University

School of Pharmacy

Dept. of Medicinal Chemistry & Pharmacognosy, Research Assistant: 1972-1973

• Responsible for independent laboratory experimentation.

Purdue University

Graduate Teaching Assistant: 1971-1972

• Responsible for setting up and teaching laboratory classes in medicinal chemistry and pharmacognosy.

Schering Corporation

Antibiotic Isolation Dept., Laboratory Assistant: 1970-1971

• Responsible for carrying out independent laboratory experiments in the antibiotic isolation/ recovery group.
John J. Dingerdissen Page 5

EDUCATION

Certificate in Business Administration University of Pennsylvania

(MBA Core Courses) Wharton Management Program

Philadelphia, PA

1983-1985

Advanced Graduate Courses Villanova University

(Organic, analytical, and biochemistry) Villanova, PA

1979-1980

Business Management Courses Temple University

Philadelphia, PA

1976-1977

M.S. Purdue University

West Lafayette, IN

Medicinal Chemistry & Pharmacognosy

Thesis: “Alkaloids of the Cactus Genus

Dolichothele”

1971-9173

B.S. Jersey City State College

Jersey City, NJ

Biology (Major) and Chemistry

1967-1971

TRAINING

Harvard University Executive Business Program, 2000

Diversity Training, 1998

Covey Leadership Training, 1994

Seven Habits of Highly Effective People, 1993

Principle Centered Leadership, 1993

Advanced Management Seminar I, 1991

MPMD Management Meeting, 1990

Leadership Conference, DuPont Pharmaceuticals, 1990

Anatomy of Persuasion, Aubuchon & Associates, 1989

How to Supervise Better, Padgett/Thompson, 1988

Multimate Word Processing Course, SK&F, 1987

Lewis Allen Management Course, Lewis Allen Association, 1987

IBM PC Course, SK&F, 1986

Lotus 1-2-3 Course, SK&F, 1986

Good Manufacturing Practice for the Pharmaceutical & Allied Health Industries, Center for Professional

Advancement, 1986

Zymark Robotics Training Course, Zymark Corp., 1985

Burger Writing Course, SK&F, 1978

Supervisory Training Course, SK&F, 1977

High Pressure Liquid Chromatography, American Chemical Society, 1977
John J. Dingerdissen Page 6

SOCIETIES & AFFILIATIONS

American Chemical Society (General and Microbial & Biochemical Technology Division)

Sigma Xi

Delaware Valley Chromatography Forum

Delaware Valley Robotics Interest Group (Vice Chairman, 1985-1986)

Pharmaceutical Manufacturers Association, Biological Section, Biotechnology Division

Committee on Product Isolation and Purification - Vice Chairman (1987-1989)

Committee on Process Development and Manufacturing - Vice Chairman (1989-1990)

Biological and Biotechnology Section - Steering Committee (1990-Present)

Pennsylvania Biotechnology Association

Board of Directors (1992-1993)

President (1994-1995)

Governor Ridge’s Network 21 - Biotechnology Task Force (1996)

PhRMA Adhoc Committee on Biological Weapons Convention (1996-Present)

International Society for Vaccines (1997)

Bioprocessing Resource Center, Inc., Board of Directors, (1997)

AWARDS

Cum laude graduate, Jersey City State College, 1971

Who’s Who in American Colleges and Universities, 1971

Graduate Teaching Assistantship, Purdue University, 1971

Research Assistantship, Purdue University, 1972

SYMPOSIA CHAIRED/ORGANIZED

PMA Biological Section Spring Meeting, “Problems in Bioprocessing,” Amelia Island, FL, May 1-3, 1989.

Biotech USA, “Production Scale Protein Purification,” San Francisco, CA, October 2-4, 1989.

PMA Biological Section Fall Meeting, “Microheterogeneity of Recombinant Protein Products,” Baltimore, MD,

September 23-26, 1990.

PMA Biological and Biotechnology Section Spring Meeting, San Francisco, CA, May 5-8, 1991.

PMA Biological and Biotechnology Section Fall Meeting, “Regulation of Recombinant Products,” Washington, DC,

September 15-18, 1991.

PMA Biological and Biotechnology Section Spring Meeting, “Experiences with the EEC Approval Process,”

Orlando, FL, May 3-6, 1992.

PMA PERI Course Instructor, Biotechnology Quality Control, “Principles of Protein Isolation and Purification,”

1992-1993.

PMA Biological and Biotechnology Section Spring Meeting, “Workshop on Multiproduct Facility Drugs,” May 10,

1994.

BIO ‘96 Biotechnology Industry Organization International Meeting, “Planning for Biotech Manufacturing,” June,

1996.

PUBLICATIONS

Sitrin, R. D., Chan, G., Dingerdissen, J. J., DeBrosse, C., Mehta, R., Roberts, G., Rottschaefer, S., Staiger, D.,

Valenta, J., Snader, K., and Hoover, J. R. 1988. Isolation and Structure Determination of Pacybasium Cerebrosides

which Potentiate the Antifungal Activity of Aculeacin. J. Antibiotics, 41, 469-480.

Dingerdissen, J. J., Sitrin, R. D., DePhillips, P. A., Giovenella, A. J., Grappel, S. F., Meta, R. J., Oh, Y. K., Pan, C.

H., Roberts, G. D., Shearer, M. C., and Nisbet, L. J. 1987. Actinoidin A2, A Novel Glycopeptide: Production,

Preparative HPLC Separation and Characterization. J. Antibiotics, 40, 165-172.
John J. Dingerdissen Page 7

Sitrin, R. D., DePhillips, P. A., and Dingerdissen, J. J. 1987. Preparative Reversed-phase HPLC of Polar

Fermentation Products. J. Ind. Microbiology, 27, 65-75.

Sitrin, R. D., Dingerdissen, J. J., DePhillips, P., Erhard, K., and Filan, J. 1986. Preparative Liquid Chromatography:

A Strategic Approach. June LC/GC Magazine.

Folena-Wassermann, G., Poehland, B., Yeung, W-K., Staiger, D., Killmer, K. D., Snader, K., Dingerdissen, J. J., and

Jeffs, P. 1986. Kibdelins (AAD-609) Novel Glycopeptide Antibiotics. II. Isolation, Purification and Structure. J.

Antibiotics, 39:1395.

Sitrin, R. D., Dingerdissen, J. J., DePhillips, P., Erhard, K., and Filan J. 1985. Recent Advances in the Preparative

Chromatography of Low Molecular Weight Substances, Application of Liquid Chromatography to the Development

of Pharmaceuticals, I. W. Wainer, Aster Publishing Corp.

Sitrin, R. D., Chan, G., DeBrosse, C., Dingerdissen, J. J., Hoover, J., Jeffs, P., Roberts, G., Rottschaefer, S., Valenta,

J., and Snader, K. 1985. Aridicins, Novel Glycopeptide Antibiotics: Isolation and Chemical Characterization. J.

Antibiotics, 38, 561-571.

Chan, J. A., Shultis, E. A., Dingerdissen, J. J., DeBrosse, C. W., Roberts, G. D., and Snader, K. M. 1984.

Chlorocardicin, A Monocyclic B-lactam from a Streptomyces Sp.: Isolation, Physiochemical Properties and

Structure Determination. J. Antibiotics, 38, 133-138.

Sitrin, R. D., DePhillips, P. A., Chan, G. W., Dingerdissen, J. J., and Snader, K. M. 1984. Practical Aspects of

Preparative Reverse Phase HPLC. Eighth International Symposium on Column Liquid Chromatography. (May 20-

25)

Sitrin, R. D., Chang, G. W., DePhillips, P. A., Dingerdissen, J. J., Valenta, J. R., and Snader, K. M. 1983.

Preparative Reversed Phase HPLC as a Recovery and Purification Process for Non-Extractable Polar Antibiotics.

ACS National Meeting, Division of Microbial and Biochemical Technology. Symposium on Recovery and

Purification of Fermentation Products, ACS Symposium Series, ACS Publishing.

Dingerdissen, J. J. and McLaughin, J. L. 1973. Cactus Alkaloids. XXII. Dolichothele surculose and Other

Dolichothele Species. Lloydia 36.419.

Dingerdissen, J. J. and McLaughlin, J. L. 1973. Cactus Alkaloids. XXI. B-Phenethylamines from Dolichothele

spaerica. Lloydia 36.419.

PRESENTATIONS

Dingerdissen, J. J., 1994. Pennsylvania Biotechnology Association 4th Annual Symposium, President’s Address:

“Reengineering the Bioenterprise,” April 26, 1994, Philadelphia, PA.

Dingerdissen, J. J., 1990. PMA Biotechnology Quality Control Training Course, Principles of Protein Isolation and

Purification.

Hayman, A. C., Reilly, T. M., Walton, H. L., Wagner, L. W., Sowa, P. C., Yates, R. A., Seetharam, R., Lischwe, M.

A., Breth, L. A., Dingerdissen, J. J., 1990. Economical multi-gram preparation of biologically active recombinant

Plasminogen Activator Inhibitor-1 from Escherichia coli. 10th International Congress of Fibrinolysis, Indianapolis,

IN.

Dingerdissen, J. J. and Rosenberg, M. 1988. The Role of Biotechnology in Pharmaceutical R&D. HPLC 88,

Washington, DC.

Folena-Wasserman, G., Inacker, R., Cohen-Silverman, C., Rosenbloom, J., Sitrin, R., DePhillips, P., Dingerdissen, J.

J. 1987. Purification strategy for recombinant DNA malaria antigens expressed in E. coli. American Society for

Biological Chemistry, Philadelphia, PA.
John J. Dingerdissen Page 8

Sitrin, R., DePhillips, P., DiPaolo, M., Dingerdissen, J. J., Inacker, R., Folena-Wasserman, G. 1987. Preparative

HPLC and biotechnology. 194th ACS National Meeting, Division of Microbial and Biochemical Technology,

Symposium in Bioseparations: Processes and Unit Operations, New Orleans, LA.

Folena-Wasserman, G., Inacker, R., Cohen-Silverman, C., Rosenbloom, J., Sitrin, R., DePhillips, P., and

Dingerdissen, J. J. 1987. Purification strategy for recombinant DNA malaria antigens expressed in E. coli.

American Society of Biological Chemists, Philadelphia, PA. Abstract No. 2037.

Del Tito, B. and Dingerdissen, J. J. 1986. Lowry assay for the measurement of total protein using robotics. Fourth

International Symposium on Laboratory Robotics, Boston, MA.

Dingerdissen, J. J., Sitrin, R., DePhillips, P., Folena-Wasserman, G., and Zabriskie, D. 1986. Malaria Vaccine:

Purification scale up strategies. Poster Session, Division of Microbial and Biochemical Technology, ACS 192nd

National Meeting, Anaheim, CA.

Folena-Wasserman, G., Inacker, R., Rosenbloom, J., Sitrin, R., DePhillips, P., Dingerdissen, J. J., Strickler, J.,

Gross, M., and Young, J. 1986. Purification of rDNA sporozoite malaria vaccine expressed in E. coli. Division of

Microbial and Biochemical Technology, ACS 192nd National Meeting, Anaheim, CA.

Nisbet, L. J., Shearer, M. C., Rake, J. B., Dingerdissen, J. J., DiPaolo, M. J., Sitrin, R. D., Allaudeen, H. S.,

Giovenella, A. J., Grappel, S. F., Carr, S. A., Heald, S. L., Roberts, G. D., Christensen, S. B., and Jeffs, P. W. 1986.

Discovery, comparative antibacterial activity, and structure elucidation of AAJ-271. A novel group of

glycopeptides. Poster Session, Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans,

LA.

Sitrin, R., DePhillips, P., and Dingerdissen, J. J. 1986. Preparative reversed-phase high performance liquid

chromatography. Biotechnology Interface Seminar, Deerfield Beach, FL.

Folena-Wasserman, G., Inacker, R., Rosenbloom, J., and Strickler, J. 1986. Use of high performance liquid

chromatography for assay, purification, and characterization of recombinant malaria vaccine candidate. 10th

International Symposium on Column Liquid Chromatography, San Francisco, CA. Abstract No. 0218.

Dingerdissen, J. J., DePhillips, P., Burke, M., DiPaolo, M., and Sitrin, R. 1986. Scaling up of difficult reversedphase HPLC separations using 150-20 micron packing. Symposium on Preparative Liquid Chromatography,

Washington, DC.

Dingerdissen, J. J., DePhillips, P., and Sitrin, R. 1986. Scaling up of difficult reversed-phase HPLC separations

using 15-20 micron packing. Second Preparative Liquid Chromatography Symposium, Washington, DC.

Chan, J. A., Simolike, G. S., Bartus, H. F., Hoffman, G. A., Johnson, R. K., Mirabelli, C. K., Dingerdissen, J. J.,

Sitrin, R. D., and Crooke, S. T. 1985. Initial biological and chemical characterization of a novel macromolecular

antitumor antibiotic AAC-345. Poster Session, Interscience Conference on Antimicrobial Agents and

Chemotherapy, Minneapolis, MN.

Dingerdissen, J. J., DePhillips, P. A., and Sitrin, R. D. 1985. Recent advances in preparative liquid chromatography

instrumentation. Preparative Scale Liquid Chromatography Symposium, Washington, DC.

Dingerdissen, J. J., King, R. T., LaDuca, S., Mehta, R. J., Phelan, C. G., Rake, J. B., Valenta, J. R., and Nisbet, L. J.

1985. Prescreens for cell wall active antibiotics and the development of effective discrimination systems for

selecting novel compounds. Poster Session, Interscience Conference on Antimicrobial Agents and Chemotherapy,

Minneapolis, MN.

Wasserman, G., Poehland, B. L., Killmer, L. B., Yeung, W. K., Jeffs, P. W., Dingerdissen, J. J., Shearer, M. C.,

Grappel, S. F., Pan, C. H., and Nisbet, L. J. 1985. Affinity isolation and characterization of new glycopeptide

antibiotics from SK&F AAD-609. Poster Session, Interscience Conference on Antimicrobial Agents and

Chemotherapy, Minneapolis, MN.
John J. Dingerdissen Page 9

Sitrin, R., DePhillips, P., Dingerdissen, J. J., and DiPaolo, M. 1985. Preparative reversed-phase chromatography of

natural products. Eastern Analytical Symposium, New York, NY.

Dingerdissen, J. J. 1983. Preparative large scale liquid chromatography. Gordon Conference on Separation and

Purification.

PATENTS

1987 - J. J. Dingerdissen, R. Mehta, M. C. Shearer, G. F. Wasserman. Kibdelosporangium aridum SKF AAD-609.

No. 4, 694,069.

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INTENTIONALLY BLANK.
CURRICULUM VITAE

June 10, 1999

Name: Gerald V. Quinnan, Jr., M.D.

Birth: September 7, 1947; Boston, Massachusetts

Spouse and Children: Married to Leigh A. Sawyer; five children

Date of Birth: September 7, 1947

Education:

1965 - 1969 Bachelor of Arts, Chemistry, College of Holy Cross, Worcester, MA 

1969 - 1973 M.D., Cum Laude, Saint Louis University, School of Medicine, Saint Louis, MO

Graduate Training: 

1973 - 1974 Internship, Straight Medicine, University Hospital, Boston University Medical 

Center, Boston, MA 

1974 - 1975 Residency, Internal Medicine, Boston University Medical Center, Boston, MA

1975 - 1977 Fellowship, Adult Infectious Diseases, Boston University Medical Center, 

Boston, MA

1977 - 1978 Research Associate, Division of Virology, Bureau of Biologics, Food and Drug

Administration (FDA),USPHS, Bethesda, MD

APPOINTMENTS:

Academic

1975 - 1977 Teaching Fellow in Medicine, Boston University Medical Center, Boston, MA

1978 - 1980 Medical Officer, Division of Virology, Bureau of Biologics, FDA

1978 - 1982 Senior Attending Physician, Infectious Disease Service, Clinical Center, National 

Institutes of Health (NIH), Bethesda, MD

1978 - 1979 Lecturer, Second Year Course on Infectious Diseases, George Washington 

University Medical Center, Washington, DC

1979 - 1985 Lecturer, FAES Course in Internal Medicine, NIH, Bethesda, MD

1980 - 1981 Director, Herpesvirus Branch, Division of Virology, Bureau of Biologics, FDA

1980 - 1981 Deputy Director (Acting), Division of Virology, Bureau of Biologics, FDA

1981 - 1988 Director, Division of Virology, Office of Biologics Research and Review, Center 

for Drugs and Biologics, FDA

1988 - 1993 Deputy Director, Center for Biologics Evaluation and Research (CBER), FDA

1990 - 1992 Acting Director, CBER, FDA

1993 Acting Director, Office of Blood Research and Review, CBER, FDA

1993 -present Professor of Preventive Medicine, Medicine and Microbiology, Department of 

Preventive Medicine and Biometrics, Uniformed Services University of the 

Health Sciences

Certification and Licensure:

Medical License: Massachusetts, Maryland, Virginia (inactive)

National Board of Medical Examiners, 1974

American Board of Internal Medicine, 1976
Scientific Societies: Alpha Omega Alpha, 1972

American Association for the Advancement of Science

American Federation for Medical Research

American Society for Clinical Investigation (1985; 37 years of age)

American Society for Microbiology

Infectious Diseases Society of America (Fellow)

Sigma Xi, 1992

Editorial Activities:

Editorial Board: Journal of Biological Standardization (1992-1997)

AIDS Research and Human Retroviruses (1985-1998)

Reviewer: New England Journal of Medicine

Annals of Internal Medicine

Journal of the American Medical Association

Journal of Clinical Investigation

The Journal of Infectious Diseases

Clinical Infectious Diseases

Journal of Virology

Journal of Immunology

Journal of AIDS

Uniformed Service:

1977 - 1980 Lieutenant Commander (0-4), USPHS

1980 - 1982 Commander(0-5), USPHS

1982 - 1992 Captain(0-6), USPHS

1992 - 1993 Rear Admiral(0-7), USPHS

1993 -present Captain(0-6), USPHS

Other Professional Activities:

1974 - 1977 Emergency Medicine, Needham Emergency Medical Corporation, Glover 

Memorial Hospital, Needham, MA

1974 - 1976 Emergency Medicine, Waltham Hospital, Waltham, MA

1974 - 1977 Consultant, Massachusetts Department of Public Health

1977 - 1978 FDA Influenza A/USSR Virus Vaccine Task Force,

1979 Panel Member US-USSR Agreement on Vaccine Research and Development

1980 - 1983 President, Parish Council, Saint Patrick's Church, Rockville, MD

1980 - 1993 Temporary Advisor, World Health Organization

1980 - 1993 USPHS Interagency Group on Vaccine Development and Availability

1981 - 1982 FDA Reye Syndrome Working Group

1981 - 1983 Consultant, Infectious Disease Associates, Fairfax, VA

1982 - 1985 USPHS Reye Syndrome Task Force, 

1981 - 1984 USPHS AIDS Executive Committee

1982 - 1988 Director, Athletic Program, Saint Patrick's Church, Rockville, MD

1984 - 1992 USPHS Executive Task Force on AIDS, Vaccine Development Subcommittee

1988 - 1993 USPHS Executive Task Force on AIDS, Blood Subcommittee

1992 - 1993 USPHS Interagency Group on Blood Safety, Chair
1993 - 1994 Chair, USAID Technical Advisory Group on Rinderpest Vaccine Development

1994 - Consultant, FDA Vaccines and Related Biologics Advisory Committee

1995 - Member Scientific Advisory Board, Aviron Corporation

1995- Ad Hoc Member, AIDS Related Research Study Section, NIH, 1995

Previous Ad Hoc Consultations for the U. S. Public Health Service Advisory Committee on 

Immunization Practices, Pan American Health Organization, Infectious Diseases 

Committee of the American Academy of Pediatrics, and for special study sections of the

National Institute of Allergy and Infectious Diseases, National Cancer 

Institute, National Institute of Neurological and Communicative Disorders and 

Stroke, and National Institute on Drug Abuse 

Participated on steering committees, program committees, and organizing committees of 

numerous national and international meetings.

Study Sections (recent):

AIDS Related Research-A, ad hoc reviewer, 1996-present.

National Cooperative Vaccine Development for AIDS, 1997

AIDS Related Research-VACC, member, 1998-present

Awards, Honors:

Elected to Alpha Omega Alpha, 1973

M.D. Degree, Cum Laude

Diplomate, American Board of Internal Medicine, 1976

Eligible, Infectious Disease Subspecialty Board, 1977

FDA Commendable Service Award, 1979

USPHS Unit Commendation, 1983

USPHS Meritorious Service Medal, 1984

Elected to American Society for Clinical Investigation, 1985

Elected to Fellow in the Infectious Disease Society of America, 1986

USPHS Outstanding Unit Citation, 1987

USPHS Unit Commendation, 1989

USPHS Citation, 1989

USPHS Distinguished Service Medal, 1990

USPHS Commendation Medal, 1991

Elected to Membership, Sigma Xi, 1992

Surgeon General's Medal for Exemplary Service, 1993

USPHS Unit Commendation, 1993

USPHS Outstanding Unit Citation, 1993

USPHS Commendation Medal, 1993

Distinguished Career Service Award, Center for Biologics Evaluation and Research, 1993

Funded Grants:

1994 - present: Uniformed Services University of the Health Sciences grant #RO87EZ, 

"Mechanisms of Neutralization Resistance of HIV-1," Principal Investigator

1995 - present: National Institutes of Health grant RO1 AI37438-01A1, "Neutralization 

Resistance of HIV-1,” Principal Investigator

1997 - present: National Institutes of Health/Fogarty International Center Grant,

#D43TW-96001, “International Training in Emerging Infectious Diseases,”
CoDirector

1998 - present: National Institutes of Health grant R21 AI42645, “Broad Neutralizing Response

to HIV/VEE Replicons,” Principal Investigator

1998 - present: USUHS Grant #87JZ01, ”Cohort Study of HTLV-1 and

Strongyloides Pathogenesis,” Coinvestigator.

Patent Applications:

1. Quinnan, GV and Zhang PF: Expression and characterization of HIV-1 envelope

protein associated with a broadly reactive neutralizing antibody response. Submitted. 1998.

Bibliography:

Publications

1. Quinnan G, Thomas E., Sussman H and Kerzner L: Prostatic carcinoma presenting as pericardial

tamponade. Cancer Treatment Reports 61:60, 1977.

2. Echeverria P, Ho MT, Blacklow N, Quinnan G, Portnoy B, Olson JG, Conklin R, DuPont HL, and

Cross JH: Relative importance of viruses and bacteria in the etiology of pediatric diarrhea in

Taiwan. J. Infect Dis 136:383-390, 1977.

3. Quinnan G, Manischewitz J and Ennis F: Cytotoxic T lymphocyte response to murine

cytomegalovirus infection. Nature 273:541-543, 1978.

4. Quinnan G and McCabe W: Erythromycin ototoxicity. Lancet 1:1160, 1978.

5. Wise T, Manischewitz J, Quinnan G, Aulakh G and Ennis F: Latent cytomegalovirus infection of

BALB/c mouse spleens detected by an explant culture technique. J Gen Virol 44:551-556, 1979.

6. Quinnan GV and Manischewitz JE: The role of natural killer cells and antibody dependent

cell-mediated cytotoxicity during murine cytomegalovirus infection. J Exp Med 150:1549-1554,

1979.

7. Kirmani N, Quinnan GV, Albrecht P and Burns W: Comparison of enzyme linked immunoassay

complement fixation, neutralizing antibody, and enhanced neutralization test for evaluation of risk

from cytomegalovirus infection in bone marrow transplant recipients. Current Chemotherapy and

Infect Dis 2:1318-1319, 1979.

8. McLaren C, Grubbs GE, Staton E, Barthlow W, Quinnan G and Ennis FA: Comparative antigenicity

and immunogenicity of A/USSR/77 influenza vaccines in normal and primed mice. Infect Immun

28:171-177, 1980.

9. Quinnan G, Manischewitz J and Ennis FA: Role of cytotoxic T lymphocytes in murine

cytomegalovirus infection. J Gen Virol 47:503-508, 1980.

10. Quinnan G, Ennis FA, Tuazon C, Wells M, Butchko G, Armstrong R, McLaren C, Manischewitz J

and Kiley S: Cytotoxic lymphocytes and antibody dependent complement-mediated cytotoxicity

induced by administration of influenza vaccine. Infect Immun 30:362-369, 1980.

11. Manischewitz JE and Quinnan GV: Antivirus antibody-dependent cell mediated cytotoxicity during

murine cytomegalovirus infection. Infect Immun 29:1050-1054, 1980.

12. Quinnan G and Ennis FA: Cell mediated immunity in cytomegalovirus infections--a review. Comp

Immun Microbiol and Infect Dis 3:283-290, 1981.

13. Quinnan GV, Kirmani N, Esber E, Saral R, Manischewitz J, Rogers J, Rook AH, Santos G and

Burns WH: Cytotoxic lymphocyte responses to cytomegalovirus infection: HLA restricted cytotoxic

T lymphocyte and non-thymic cytotoxic lymphocyte activity during cytomegalovirus infection of

bone marrow transplant recipients. J Immunol 126:2036-2041, 1981.
14. Kirmani N, Ginn RK, Mittal KK, Manischewitz JF and Quinnan GV: Cytomegalovirus specific

cytotoxicity mediated by non-T lymphocytes from peripheral blood of normal volunteers. Infect

Immun 34:441-447, 1981.

15. Quinnan GV, Manischewitz JF and Kirmani N: Involvement of natural killer cells in the

pathogenesis of murine cytomegalovirus interstitial pneumonitis and the immune reponse to

infection. J Gen Virol 58:173-180, 1982.

16. Quinnan GV, Kirmani N, Rook AH, Manischewitz JF, Jackson L, Moreschi G, Santos G, Saral R

and Burns W: Cytotoxic T cells in cytomegalovirus infection HLA-restricted T-lymphocyte and

non-T lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in

bone marrow transplant recipients. N Engl J Med 307:7-13, 1982.

17. Iltis J, Castellano GA, Gerber P, Le C, Vujcic LK and Quinnan GV: Comparison of the Raji cell line

fluorescent antibody to membrane antigen test and the enzyme linked immunosorbent assay for

determination of immunity to varicella-zoster virus. J Clin Microbiol 16(5):878-884, 1982.

18. Rook AH, Tsokos GC, Quinnan GV, Balow JE, Ramsey KM, Stocks N, Phelan MA and Djeu JY:

Cytotoxic antibodies to natural killer cells in systemic lupus erythematosus. Clin Immunol

Immunopath 24:179-185, 1982.

19. Gross PA, Quinnan GV, Gaerlan PF, Denning CR, Davis A, Lazicki M and Bernius M: Potential for

single high-dose influenza immunization in unprimed children. Pediatrics 70:982-986, 1982.

20. Brown AE, Quesada O, Steinherz PG, Miller DR, Kellick MG, Armstrong D, Gross PA, Lazicki

ME, Davis AE and Quinnan GV: Immunization against influenza in children with cancer: Results

of a three-dose trial. J Infect Dis 145:126, 1982.

21. Quinnan GV, Schooley R, Dolin R, Ennis FA, Gross P and Gwaltney JM: Serologic responses and

systemic reactions in adults after vaccination with monovalent A/USSR/77 and trivalent

A/USSR/77, A/Texas/77, B/Hong Kong/72 influenza vaccines. Rev Infect Dis 5:748-757, 1983.

22. La Montagne J, Noble G, Quinnan GV, Curlin GT, Blackwelder WE, Smith JI, Ennis FA and

Bozeman M: Summary of clinical trials of inactivated influenza vaccine-1978. Rev Infect Dis

5:723-736, 1983.

23. Gross PA, Quinnan GV, Gaerlon PF, Denning CR, Lazicki M, Davis A and Bernius M: Influenza

vaccines in children: comparison of new cetyltrimethyl ammonium bromide (CTAB) and standard

ether-treated (ET) vaccines. Amer J Dis Child 137:26-28, 1983.

24. Asano Y, Albrecht P, Vujcic L, Quinnan GV and Takahashi M: Evaluation of humoral immunity to

varicella-zoster virus by an enhanced neutralization test and by the fluorescent antibody to membrane

antigen test. Arch Virol 75:225-228, 1983.

25. Asano Y, Albrecht P, Vujcic L, Quinnan GV, Kawakami K and Takahashi M: Five-year follow up of

recipients of live varicella vaccine using enhanced Nt and FAMA assays. Pediatrics 72:291-294,

1983.

26. Rook AH, Masur H, Lane HC, Frederick W, Kasahara T, Macher AM, Djeu JY, Manischewitz J,

Jackson L, Fauci A and Quinnan GV: Interleukin-2 enhances the depressed natural killer and

cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune

deficiency syndrome. J Clin Invest 72:398-403, 1983.

27. Macher A, Reichert C, Straus S, Longo D, Parrillo J, Lane C, Fauci AS, Rook AH, Manischewitz J

and Quinnan GV: Death in the AIDS patient: role of cytomegalovirus. N Engl J Med 309:1454,

1984 (letter).

28. Quinnan GV, Burns WH, Kirmani N, Rook AH, Manischewitz JF, Jackson L, Santos GW and Saral

R: HLA-restricted cytotoxic T lymphocytes are an early immune response and important defense

mechanism in cytomegalovirus infections. Rev of Infect Dis 6:156-163, 1984.
29. Burlington DB, Djeu JY, Wells MA, Kiley SC and Quinnan GV: Large granular lymphocytes

provide an accessory function in the in vitro development of influenza A virus-specific cytotoxic T

cells. J Immunol 132-3154-3158, 1984.

30. Grimley PM, Kang Y-H, Frederick W, Rook AH, Kostianovsky M, Sonnabend JA, Macher AM,

Quinnan GV, Friedman RM and Masur H: Interferon-related leukocyte inclusions in acquired

immunodeficiency syndrome: localization in T-cells. Am J Clin Path 81:147-155, 1984.

31. Quinnan GV, Delery M, Rook AH, Frederick WR, Epstein J, Manischewitz J, Jackson L, Ramsey K,

Mittal K, Plotkin SA and Hilleman M: Comparative virulence and immunogenicity of the Towne

strain and a nonattenuated strain of cytomegalovirus. Ann of Intern Med 101:478-483, 1984.

32. Quinnan GV, Masur H, Rook AH, Armstrong G, Frederick WR, Epstein J, Manischewitz JF, Macher

AM, Jackson L, Ames J, Smith HA, Parker M, Pearson G, Parrillo J, Mitchell C and Straus SE:

Herpesvirus infections in the acquired immune deficiency syndrome. JAMA 252:72-77, 1984.

33. Rook AH, Quinnan GV, Frederick WJ, Manischewitz JF, Kirmani N, Dantzler TJ, Lee BB and

Currier CB: Importance of cytotoxic lymphocytes during cytomegalovirus infection in renal

transplant recipients. Amer J Med 76:385-392, 1984.

34. Siegel JP, Rook AH, Djeu JY and Quinnan GV: Interleukin-2 therapy in infectious diseases:

rationale and prospects. Infection (12)4:298-302, 1984.

35. Lane HC, Siegel J, Rook AH, Masur H, Galmann EP, Quinnan GV and Fauci AS: Use of

interleukin-2 in patients with acquired immunodeficiency syndrome. J Biol Resp Mod 3:512-516,

1984.

36. Lane HC, Masur H, Longo DL, Klein HG, Rook AH, Quinnan, GV, Steis RG, Macher A, Whalen G,

Edgar LC and Fauci AS: Partial immune reconstitution in a patient with the acquired

immunodeficiency syndrome. N Engl J Med 311:1099-1103, 1984.

37. Frederick WR, Epstein JS, Gelmann EP, Rook AH, Armstrong GR, Djeu JY, Jackson L,

Manischewitz, JF, Enterline J, Jacob J, Masur H and Quinnan GV: Viral infections and

cell-mediated immunity in immunodeficient homosexual men with Kaposi's Sarcoma treated with

human lymphoblastoid interferon. J Infect Dis 153:162-170, 1985.

38. Siegel J, Djeu J, Stocks N, Masur H, Gelmann J and Quinnan G: Sera from patients with the

acquired immunodeficiency syndrome inhibit production of interleukin-2 by normal lymphocytes. J

Clin Invest 75:1957-1964, 1985.

39. Rook AH, Hooks JJ, Quinnan GV, Lane HC, Manischewitz JF, Macher AM, Masur H, Fauci AS and

Djeu JY: Interleukin-2 enhances the natural killer cell activity of acquired immunodeficiency

syndrome patients through a gamma-interferon-independent mechanism. J Immunol 134:1503-1507,

1985.

40. Epstein JS, Frederick WR, Rook AH, Jackson L, Manischewitz JF, Mayner RE, Masur H, Enterline

JC, Djeu JY and Quinnan GV: Selective defects in cytomegalovirus- and mitogen-induced

lymphocyte proliferation and interferon release in patients with the acquired immunodeficiency

syndrome. J Infect Dis 152:727-733, 1985.

41. Rook AH, Manischewitz JF, Frederick WR, Epstein JS, Jackson L, Gelmann E, Steis R, Masur H

and Quinnan GV: Deficient, HLA-restricted cytomegalovirus-specific cytotoxic T cells and natural

killer cells in patients with the acquired immunodeficiency syndrome. J Infect Dis 152(3):627-630,

1985.

42. Siegel JP, Lane HC, Stocks NI, Quinnan GV and Fauci AS: Pharmacokinetics of

lymphocyte-derived and recombinant DNA-derived interleukin-2 after intravenous administration to

patients with the acquired immunodeficiency syndrome. J Biol Resp Mod 4:596-601, 1985.

43. Hurwitz E, Barrett MJ, Bregman D, Gunn WJ, Schonberger LB, Fairweather WR, Drage JS, La

Montagne JR, Kaslow RA, Burlington DB, Quinnan GV, Parker R, Phillips K, Pinsky P, Dayton D
and Dowdle WR: Public Health Service study on reye syndrome and medications: report of the

pilot phase. N Engl J Med 313:849-857, 1985.

44. Preble OT, Rook AH, Steis R, Silverman RH, Krause D, Quinnan, GV, Masur H, Jacob J, Longo D

and Gelmann EP: Interferon-induced 2'-5' oligoadenylate synthetase during interferon-alpha in

homosexual men with Kaposi's sarcoma: marked deficiency in biochemical response to interferon in

patients with acquired immunodeficiency syndrome. J Infect Dis 152:457-465, 1985.

45. Quinnan GV, Siegel JP, Epstein JS, Manischewitz MS, Barnes S and Wells, MA: Mechanisms of

T-cell functional deficiency in the acquired immunodeficiency syndrome. Ann Intern Med

103:710-714, 1985.

46. Petricciani JC, Seto B, Wells M, Quinnan GV, McDougal JS and Bodner A: An analysis of serum

samples positive for HTLV-III antibodies(letter). New Eng J Med 313:47-48, 1985.

47. Saah AJ, Neufeld R, Rodstein M, La Montagne JR, Blackwelder WC, Gross P, Quinnan GV and

Kaslow RA: Influenza vaccine and pneumonia mortality in a nursing home population. Arch Intern

Med 146:2353-2357, 1986.

48. Quinnan GV, Wells MA, Wittek AE, Phelan MA, Mayner RE, Feinstone S, Purcell RH and Epstein

JS: Inactivation of human T lymphotropic virus, type III (HTlV-III) by heat, chemicals and

irradiation. Transfusion 26(5):481-483, 1986.

49. Masur H, Lane HC, Palestein A, Smith PD, Manischewitz J, Stevens G, Fujikawa L, Macher AM,

Nussenblatt R, Baird B, Megill M, Wittek A, Quinnan GV, Parrillo JE, Rook AH, Eron LJ, Poretz

DM, Goldenberg RI, Fauci AS and Gelmann EP: Effect of 9-(1,3 dihydroxy-2-propoxymethyl)

guanine on serious cytomegalovirus disease in eight immunosuppressed homosexual men. Ann

Intern Med 104:41-44, 1986.

50. Wells MA, Wittek AE, Epstein JS, Marcus-Sekura C, Daniel S, Tankersley M, Preston S and

Quinnan GV: Inactivation and partitioning of human T-cell lymphotropic virus, type III, during

ethanol fractionation of plasma. Transfusion 26:210-213, 1986.

51. Palestine AG, Stevens G, Lane C, Masur H, Fujikawa LS, Nussenblatt RB, Rook AH, Manischewitz

J, Baird B, Megill M, Quinnan G, Gelmann E and Fauci AS: Treatment of cytomegalovirus retinitis

with dihydroxy propoxymethyl guanine. Am J Opthalmology 101:95-101, 1986.

52. Wells M, Wittek A, Epstein J, Marcus-Sekura C, Daniel S, Phelan M, Tankersley D, Preston S, Zuck

T and Quinnan G: Reduction of LAV-HTLV-III by the Cohn-Oncley process. Vox Sanguinis

51:256, 1986.

53. Hendry RM, Wells MA, Phelan MA, Schneider AL, Epstein JS and Quinnan GV: Antibodies to

simian immunodeficiency virus in African green monkeys in Africa in 1958-62. Lancet 2:455, 1986.

54. Zuck, T.F., M.S. Preston, D.L. Tankersley, M.A. Wells, A.E. Wittek, J.E. Epstein, S. Daniel, M.

Phelan, and G.V.J. Quinnan. 1986. More on partitioning and inactivation of AIDS virus in immune

globulin preparations [letter]. N Engl J Med 1454-1455.

55. Epstein J, Grimley P, Moffitt A, Manischewitz J and Quinnan G: Prevalence of antibodies to

HTLV-III, herpesviruses, and hepatitis B virus in homosexual men, hemophilia patients, and controls

in Budapest. J Infect Dis 155:134-136, 1987.

56. Quinnan GV and Manischewitz JF: Genetic resistance to murine cytomegalovirus infection is

mediated by interferon-dependent and independent, H2-linked or background genes for intrinsic

cellular resistance to infection. J Virol 61:1875-1881, 1987.

57. Chen KS, Burlington DC and Quinnan GV: Active synthesis of protective hemagglutinin-specific

IgA by lung cells of mice that were immunized intragastrically with inactivated influenza virus

vaccine. J Virol 61:2150-2154, 1987.

58. King JC, Gross PA, Denning CR, Gaerlan PF, Wright PF and Quinnan GV: Comparison of live and

inactivated influenza vaccine in high risk children. Vaccine 5:234-238, 1987.
59. Marcus, CJ, Woerner AW, Shinozuka K, Zon G and Quinnan GV: Comparative inhibition of

chloramphenicol acetyltransferase gene expression by antisense oligonucleotide analogues having

alkyl phosphotriester, methylphosphonate and phosphorothioate linkages. Nucleic Acids Res

60. Gross PA, Weksler MR, Quinnan GV, Douglas RG, Gaerlan PF and Denning CR: Immunization of

elderly people with two doses of influenza vaccine. J Clin Micro 25:1763-1765, 1987.

61. Anderson MC, Baer H, Frazier DJ and Quinnan GV: The role of specific IgE and beta-propiolactone

in reactions resulting from booster doses of human diploid cell rabies vaccine. J Allergy Clin

Immunol 80:861-868, 1987.

62. Hurwitz E, Barrett MJ, Bregman D, Gunn WJ, Pinsky P, Schonberger LB, Drage JS, Kaslow RA,

Burlington DB, Quinnan GV, et al: Public Health Service study of Reye syndrome and medications:

Report of the main study. JAMA 257:1905-1911, 1987.

63. Wittek AE, Phelan MA, Wells MA, Vujcic LK, Epstein JS, Lane HC and Quinnan GV: Detection of

human immunodeficiency virus core protein in plasma by enzyme immunoassay: Association of

antigenemia with symptomatic disease and T-helper cell depletion. Ann of Intern Med 107:286-292,

1987.

64. Krilov LF, Kirmani N, Hendry RM, Wittek AE and Quinnan GV: Longitudinal serologic evaluation

of an infant with acquired immunodeficiency syndrome. Ped Infect Dis J 6:1066-1067, 1987.

65. Gross PA, Quinnan GV, Rodstein M, LaMontagne J, Kaslow RA, Saah AH, Wallenstein S, Neufeld

R and Libow LW: Association of influenza immunization with of reduction mortality in an elderly

population: A prospective study. Ann Intern Med 146:562-565, 1988.

66. Smith PD, Lane HC, Gill VJ, Manischewitz JF, Quinnan GV, Fauci AS and Masur H: Intestinal

infections in patients with the acquired immunodeficiency syndrome (AIDS): Etiology and response

to therapy. Ann Intern Med 108:328-333, 1988.

67. Marcus-Sekura CJ, Woerner AM, Klutch M and Quinnan GV: Reactivity of an HIV gag gene

polypeptide expressed in E coli with sera from AIDS patients and monoclonal antibodies to gag.

Biochimica et Biophysica Acta 949:213-223, 1988.

68. Liang SM, Lee N, Zoon KC, Manischewitz JF, Chollet A, Liang CM and Quinnan GV: Biological

characterization of human-interleukin-2 mutant proteins. J Biol Chem 263:4768-4772, 1988.

69. Albini A, Mitchell CD, Thompson EW, Seeman R, Martin GR, Wittek AE and Quinnan GV:

Invasive activity and chemotactic response to growth factors by Kaposi's sarcoma cells. J Cell

Biochem 36:369-376, 1988.

70. Shepp DH, Daguillard F, Mann D and Quinnan GV: Human class I MHC-restricted cytotoxic

T-lymphocytes specific for human immunodeficiency virus envelope antigens. AIDS 2:113-117,

1988.

71. Katzenstein DA, Sawyer LA and Quinnan GV: Editorial review: Issues in the evaluation of AIDS

vaccines. AIDS 2:151-155, 1988.

72. Gross, PA, Quinnan GV, Weksler ME, Gaerlan PF and Denning CR: Immunization of elderly people

with high doses of influenza vaccine. J Am Ger Soc 36:209-212, 1988.

73. Vujcic LK, Shepp DH, Klutch M, Wells MA, Hendry RN, Wittek AE, Krilov L and Quinnan GV:

Use of a sensitive neutralization assay to measure the prevalence of antibodies to the human

immunodeficiency virus. J Infect Dis 157:1047-1050, 1988.

74. Cooper E, Vujcic L and Quinnan GV: HLA-restricted, cytotoxic T cells responses of adult

lymphocytes to varicella zoster virus in vitro. J Infect Dis 158:780-788, 1988.

75. Gross PA, Rodstein M, LaMontagne J, Kaslow RA, Saah AJ, Wallenstein S, Neufeld R, Denning C,

Gaerlan P and Quinnan GV: Epidemiology of acute respiratory illness during an influenza outbreak

in a nursing home. A prospective study. Arch Int Med 148:599-561, 1988.
76. Shepp DH, Chakrabarti S, Moss B and Quinnan GV: Antibody-dependent cellular cytotoxicity

specific for the envelope antigens of human immunodeficiency virus. J Infect Dis 157:1260-1264,

1988.

77. Chen KS and Quinnan GV: Induction, persistence and strain specificity of hemagglutinin-specific

secretory antibodies in lungs of mice after intragastric administration of inactivated influenza virus

vaccine. J Gen Virol 69:2779-2784, 1988.

78. Baranski B, Armstrong G, Truman JT, Quinnan GV, Straus SE, Young NS: Epstein-Barr virus in the

bone marrow of patients with aplastic anemia. Ann Intern Med 109:695-704, 1988.

79. Lane HC, Feinberg J, Davey V, Deyton L, Baseler M, Manischewitz J, Masur H, Kovacs JA, Herpin

B, Walker R, Metcalf JA, Salzman N, Quinnan G and Fauci AS: Anti-retroviral effects of

interferon-alpha in AIDS-associated Kaposi's sarcoma. Lancet 1218, 1988.

80. Gross PA, Quinnan GV, Rodstein M, LaMontagne JR, Kaslow RA, Saah AJ, Wallenstein S, Neufeld

R, Denning C and Gaerlan P: Association of influenza immunization with reduction in mortality in

an elderly population. Arch Intern Med 148:562-565, 1988.

81. Singer C, Knauert F, Bushar G, Klutch M, Lundquist R and Quinnan GV: Quantitation of poliovirus

antigens in inactivated viral vaccines by enzyme-linked immunosorbent assay using animal sera and

monoclonal antibodies. J Biol Stand 17:137-150, 1989.

82. Gross PA, Quinnan GV, Weksler ME, Usha S, Douglas RG, Jr.: Relation of chronic disease and

immune response to influenza vaccine in the elderly. Vaccine 7:303-308, 1989.

83. Holland HK, Saral R, Rossi JJ, Donnenberg AD, Burns WH, Beschorner WM, Farzadegan H, Jones

RJ, Quinnan GV, Vogelsang GB, Vriesendorp HM, Wingard JR, Zaia JA, Santos GW. Allogeneic

bone marrow transplantation, Zidovudine and human immunodeficiency virus type 1 infection:

Studies in a patient with non-Hodgkin lymphoma. Ann Int Med 111: 973-981, 1989.

84. Chen KS, Quinnan GV. Efficacy of inactivated influenza vaccine delivered by oral administration.

Curr Top Microbiol Immunol 146: 101-6, 1989.

85. Chen, K.S. and G.V.J. Quinnan. 1988. Induction, persistence and strain specificity of

haemagglutinin- specific secretory antibodies in lungs of mice after intragastric administration of

inactivated influenza virus vaccines. J Gen Virol 69:2779-2784.

86. Sawyer LA, Katzenstein DA, Hendry RM, Boone EJ, Vujcic LK, Williams CC, Zeger SL, Saah AJ,

Rinaldo, RR, Jr., Phair JP, Giorgi JV, Quinnan, GV, Jr.: Possible beneficial effects of neutralizing

antibodies and antibody-dependent, cell-mediated cytotoxicity in human immunodeficiency virus

infection. AIDS Res and Human Retrovir 6:341-356, 1990.

87. Vujcic L, Katzenstein D, Martin M, Quinnan GV: International collaborative study to compare

assays for antibodies that neutralize human immunodeficiency virus. AIDS Res and Human Retro

6(7):847-853, 1990.

88. Katzenstein DA, Vujcic, LK, Latif A, Boulos R, Halsey NA, Quinn TC, Rastogi SC, Quinnan, GV:

Human immunodeficiency virus neutralizing antibodies in sera from North America and Africa. J

AIDS 3: 810-816, 1990.

89. Sawyer LA, Metcalf JA, Zoon KC, Boone EJ, Kovacs JA, Lane HC, !uinnan GV. Effects of

interferon-a in paatieonts with AIDS-associeated Kaposi's sarc9oma are related to blood interferon

levels and dose. Cytokine 2: 247-252, 1990.

90. Carrow EM, Vujcic LK, Glass WL, Seamon KB, Rastogi SC, Hendry RM, Boulos R, Nzila N,

Quinnan GV: High prevalence of antibodies to the gp120 V3 region principal neutralizing

determinant of HIV-1MN in sera from Africa and the Americas. AIDS Res and Human Res

7(10):831-838, 1991.

91. Wittek AE, Mitchell CD, Armonstrong GR, Albini A, Martin GR, Seemann R, Levenbook IS,

Wierenga DE, Ridge J, Dunlap RC, Lundquist ML, Steis RG, Longo DL, Muller J and Quinnan GV:
Propagation and properties of Kaposi's sarcoma-derived cell lines obtained from patients with AIDS:

similarity of cultured cells to smooth muscle cells. AIDS 5(12):1485-1493, 1991.

92. Hendry RM, Parks DE, Campos-Mello DLA, Quinnan GV, Galvao-Castro B: Lack of evidence for

Sawyer LA, Carrow E, Snoy PJ, Hewlett IK, Quinnan GV, Anand R: Variable infections with and

serologic responses of rabbits to five different HIV-1 strains, including one neural tissue isolate.

Microbios 71:243-255, 1992.

93. Vujcic L, Quinnan GV: Human sera for use as reference reagents in assays for neutralizing

antibodies against human immunodeficiency virus type 1. AIDS Res and Hum Retrovir 11: 783-787,

1995.

94. Gross PA, Denning CR, Gaerlan PF, Bonelli F, Bernius Sr M, Dran S, Monk G, Burwicz M,

Quinnan GV Jr, and Levandowski R: Annual Influenza vaccination: Immune response in patients

over 10 years. Vaccine 14:1280-4, 1996.

95. Park EJ, Vujcic LK, Anand R, Theodore TS, and Quinnan GV,. Mutations in both gp120 and gp41

are responsible for the broad neutralization resistance of HIV-1 MN to antibodies directed at V3 and

non-V3 epitopes. J Virol 72: 7099-7107, 1998.

96. Quinnan, GV, Zhang PF, Fu DW, Dong M, Gao J, and Margolick J. Evolution of Neutralizing

Antibody Response Against HIV Type 1 Virions and Pseudovirions in Multicenter AIDS Cohort

Study Participants. AIDS Res Human Retrovir. 14: 939-949, 1998.

97. Quinnan, G.V., Zhang, P.F., Fu, D.W., Dong, M., Alter, H.J. and international collaborators.

Expression and characterization of HIV-1 envelope protein associated with a broadly reactive

neutralizing antibody response. AIDS Res Human Retrovir, 15, 561-570, 1999.

98. Zhang PF, Chen X, Fu DW, Margolick JB, and Quinnan GV Jr. Primary virus envelope cross

reactivity of the broadening neutralizing antibody response during early chronic HIV-1 infection in

Multicenter AIDS Cohort Study (MACS) participants. J Virol. 73: 5225-30, 1999.

99. Park, E.J., L.K. Vujcic, R. Anand, T.S. Theodore, and G.V. Quinnan. 1998. Mutations in both

gp120 and gp41 are responsible for the broad neutralization resistance of variant human

immunodeficiency virus type 1 MN to antibodies directed at V3 and non-V3 epitopes. J Virol 72:

7099-7107.

100.Park, E.J. and G.V. Quinnan. 1999. Both Neutralization Resistance and High Infectivity

Phenotypes are Caused by Mutations of Interacting Residues in the HIV-1 gp41 Leucine

Zipper and the gp120 Receptor- and Coreceptor-Binding Domains. J Virol 73: 5707-5713.

101. Chabot DJ, Zhang PF, Quinnan GV, and Broder CC. Mutagenesis of CXCR4 identifies

important domains for human immunodeficiency virus type 1 X4 virus envelope mediated

membrane fusion and virus entry and reveals cryptic coreceptor activity for R5 isolates. J

Virol. 1999 73:6598-6609

102. Park EJ, Gorny MK, Zolla-Pazner S, and Quinnan GV. A global neutralization resistance

phenotype of HIV-1 is determined by distinct mechanisms mediating enhanced infectivity and

conformational change of the envelope complex. J. Virol. 74: In press, May, 2000.

103. Zhang PF, Chen X, Park EJ, Margolick JB, Robinson JE, Zolla-Pazner S, Quinnan GV. Immune

response to an unusual conformational epitope in variable region 3 of the HIV-1 envelope

glycoprotein accounts for extensive primary virus cross reactive neutralizing antibodies in a

reference human serum. Submitted for publication.

Abstracts: More than 200 abstracts published

Books Chapters and Non-refereed Publications:
1. Quinnan G and Bozeman M: Production and delivery of influenza vaccines. Proceedings of 14th

Immunization Conference, 1979.

2. Quinnan GV: Regulatory issues with new technology interferon. Am Pharm NS21:21-24, 1981.

3. Daisy JA, Tolpin MD, Quinnan GV, Rook AH, Murphy BR, Mittal K, Clements ML, Mullinix MG,

Kiley SC and Ennis FA: Cytotoxic cellular immune responses during influenza A infection in human

volunteers. In: Bishop DHL and Compans RW, eds. The Replication of Negative Strand Viruses, pp.

443-448, 1981.

4. Rook AH and Quinnan GV: Cytomegalovirus infection and blood transfusion. In: Tabor E, ed.

Infectious Complications of Blood Transfusion. Academic Press, New York pp 45-64, 1982.

5. Rook AH and Quinnan GV: Cell mediated immunity to human cytomegalovirus. In: Ennis FA, ed.

Human Immunity to Viruses. Academic Press. New York pp 241-257, 1982.

6. Rook AH, Frederick WH, Burns WH, Djeu JY, Kirmani N, Jackson L, Manischewitz J, Saral R,

Santos GW and Quinnan GV: Natural killer cell activity and interferon release predict survival from

viral infection in bone marrow transplant recipients. Transpl Proceed 15:1773-1776, 1983.

7. Quinnan GV: AIDS: solutions on the horizon. In: Encyclopedia Britannica, Medical and Health

Annual pp 186-190, 1984.

8. Quinnan GV, Rook AH, Frederick WR, Manischewitz JF, Epstein J, Siegel J, Masur H, Macher AM,

Mitchell C, Armstrong G and Djeu J: Prevalence, clinical manifestations, and immunology of

herpesvirus infections in the acquired immunodeficiency syndrome. Ann NY Acad of Sci 437:200-206,

1984.

9. Quinnan GV: Viral immunology. In: Belshi R, ed. Textbook of Human Virology. PSG Publishing

Company, Inc., Littleton MA pp 103-138; 1984.

10. Quinnan GV and Rook AH: The importance of cytotoxic cellular immunity in the protection from

cytomegalovirus infection. In: Plotkin SA ed. Pathogenesis and Prevention of Cytomegalovirus

Infections. Alan R. Liss, New York pp 245-262, 1984.

11. Epstein JS and Quinnan GV: Prevention of herpes simplex virus diseases in man. Clinics in

Dermatology 2:133-146, 1984.

12. Epstein JS, Frederick WJR, Rook AH, Masur H, Turner W, Manischewitz JF, Ames J, Fauci AS,

Lane HC and Quinnan GV: Cytomegalovirus (CMV)-specific humoral and cellular immune responses

in healthy and immunodeficient homosexual men. In: Plotkin SA ed. Pathogenesis and Prevention of

Cytomegalovirus Infections. Alan R. Liss, New York pp 396-399, 1984.

13. Rook AH, Frederick W, Manischewitz JF, Epstein JS, Jackson L, Lee BB, Currier CB and Quinnan

GV: Correlation of clinical outcome of cytomegalovirus infection and immunosuppression with virus

specific cytotoxic lymphocyte responses in renal transplant recipients. In: Plotkin SA, ed. Pathogenesis

and Prevention of Cytomegalovirus Infections. Alan R. Liss, New York pp 473-475, 1984.

14. Rook AH, Smith WJ, Burdick JF, Manischewitz JF, Frederick W, Siegel JP, Williams GM and

Quinnan GV: Virus-specific cytotoxic lymphocyte responses are predictive of the outcome of

cytomegalovirus infection of renal transplant recipients. Transplant Proc 16:1466-1469, 1984.

15. Preble OT, Rook AH, Quinnan GV, Vilcek J, Friedman RM, Steis R, Gelmann EP and Sonnabend

JA: Role of interferon in AIDS. Ann N Y Acad Sci 437:65-75, 1984.

16. Rook AH, Zorn S, Burns WH, Manischewitz JF, Frederick W, Saral R, Santos GW and Quinnan

GV: Interleukin-2 enhances the antiviral immune responses of bone marrow transplant recipients.

Transplant Proceed 17:480-481, 1985.

17. Quinnan GV: Cell-mediated immunity in cytomegalovirus infections. In: Roizman B and Lopez C

eds. The Herpes Viruses. Plenum Publishing Corp 4:121-145, 1985.

18. Epstein JS, Mayner RE, Phelan MA, Qi Y and Quinnan GV: Approaches for the development of a

vaccine against human cytomegalovirus. In: Lerner RA, Chanock RM and Brown F eds. Vaccines '85:
Molecular and Chemical Basis of Resistance to Parasitic, Bacterial and Viral Diseases. New York:

Cold Spring Harbor Laboratories. pp 291-295, 1985

19. Quinnan GV: Protein contaminants in biologic products derived from cell substrates. In: Hopps

HE and Petricciani JC, eds. Abnormal Cells, New Products and Risk. Tissue Culture Association,

Gaithersburg, MD, pp. 41-47, 1985.

20. Phelan, MJ, Hall JW, Wells M, Kowalski M, Vujcic L, Quinnan GV and Epstein J: HTLV-III/LAV

particle-associated proteins: I. Virus purification, inactivation and basic characterization. In: L'Italien

JJ ed. Recent Advances in Protein Chemistry. Plenum Press, New York, NY, 1986.

21. Wittek A and Quinnan GV: Opportunistic viral infections in the acquired immunodeficiency

syndrome. In: Rondelli EG, ed. AIDS, Piccin, Padova pp 203-232, 1987.

22. Quinnan GV: Current developments and future prospects for AIDS vaccines. Proccedings, Surgeon

General's Conference on Children with HIV Infection and Their Families, pp 44-47, 1987.

23. Katzenstein DA, Sawyer LA and Quinnan GV: Human immunodeficiency virus. In: Plotkin SA

and Mortimer EA, Jr eds. Vaccine. WB Saunders Co., Philadelphia, PA 1988.

24. Sawyer, LA, Katzenstein DA and Quinnan GV: Regulatory concerns regarding AIDS vaccine

development. AIDS and Public Policy J 3:36-45, 1988.

25. Marcus-Sekura CJ and Quinnan GV: Risks and benefits of vaccinia-vectored vaccine use from the

regulatory perspective. 2nd Forum in Virology. Res Virol 140:467-469, 1989.

26. Chen KS and Quinnan GV: Efficacy of inactivated influenza vaccine delivered by ordal

administration. In: Mestecky J and McGhee JR eds. Current Topics in Microbiology and Immunology.

Springer-Verlag Berline, Heidelberg, 146:101-106, 1989.

27. Quinnan, GV: Constraints on development of recombinant vaccinia virus vaccines. In:

Proceedings of the Ninety-Third Annual Meeting of the United States Animal Health Association

Meeting October 28, 1989.

28. Quinnan GV: Immunization against viral diseases. In: Galasso G, Whitley R and Merigan TC, eds.

Antiviral Agents and Viral Diseases of Man, third edition, Raven Press, New York, 727-769, 1990.

29. Wittek AE and Quinnan GV: AIDS Vaccines Regulatory, Scientific, and Ethical Issues. In:

Bolognesi D and Putney S, eds. AIDS Vaccine Research and Clinical Trials, Marcel Dekker, Inc., New

York, 439-468, 1990.

30. Wittek AE and Quinnan GV: Immunology of viral infections. In: Belshe RB ed. Textbook of

Human Virology, sec. ed., Yearbook Publishers 116-155, 1991.

31. Quinnan, G.V.J. 1991. Licensing of allergen patch tests [comment]. Ann Allergy 67:550-551.

32. Quinnan, G.V.J. 1991. FDA's Center for Biologics Evaluation and Research comments on the Report

of the expert panel [letter; comment]. Public Health Rep 106:31

31. Quinnan GV: Interferons and biological response modifiers. In: Gorbach SL, Bartlett JG, and

Blacklow NR, eds. Infectious Diseases, W.B. Saunders, Co., 85-89, 1992.

32. Gross PA, Denning CR, Gaerlan PF, Bonelli J, Bernius M, Dran S, Monk G, Burwicz M, Quinnan

GV, Levandowski R: Benefit of annual influenza vaccination in patients with cystic fibrosis. In,

Hanoun C and Kendall A, Options for the Control of Influenza, Elsevier, New York, 1993, pp 417-421.

33. Quinnan GV: Immunization against viral diseases. In: Galasso G, Whitley R and Merigan TC, eds.

Antiviral Agents and Human Viral Diseases, fourth edition, Raven Press, New York, 1997, pp 791-834.

34. Quinnan GV: Cytokines in the treatment and prevention of infectious diseases. In: Gorbach SL,

Bartlett JG, and Blacklow NR, eds. Infectious Diseases, second edition, Raven Press, 1997, pp 92-100.

Books:

Quinnan, G. V., ed. Vaccinia Viruses as Vectors of Vaccine Antigens. Elsevier, New York, 1985.
RITA LAPPIN WELLS, Ph.D.

Dr. Wells is the Deputy Executive Director and Chief Operating Officer of the Committee

for Purchase from People Who Are Blind or Severely Disabled. The Committee is an independent

Federal agency responsible for managing the Javits-Wagner-O’Day (JWOD) Program, through

which Federal activities purchase goods and services from nonprofit agencies associated with the

National Industries for the Blind (NIB) and NISH, serving people with other severe disabilities. 

JWOD Program procurements provide high quality goods and services needed for the operation

of the federal government, and also provide employment and job skills training for more than

34,000 people who are blind or have other severe disabilities.

Dr. Wells has an extensive background in Federal acquisition and management. She began

her career in a contracting intern program with the Department of Defense (DoD) and went on to

hold various acquisition related positions including as the program manager of a joint DoD-wide

program, a Procuring Contracting Officer (TOMAHAWK Cruise missile program), an

Administrative Contracting Officer for the Defense Logistics Agency, and a contract price analyst

with the Pacific Command of the Air Force. She also was a member of the acquisition

management faculty at both the Industrial College of the Armed Forces (ICAF), and the Air Force

Institute of Technology (AFIT). 

In addition, Dr. Wells teaches business administration and contract management courses for

the University of Virginia. She also is a Faculty Associate at Johns Hopkins University for

graduate courses in leadership and global strategic management. 

She holds a doctorate from The Ohio State University, an MBA from Southern Illinois

University, and a BA from the University of Illinois. Dr. Wells is a graduate of the Industrial

College of the Armed Forces and the Department of Defense Senior Executive Leadership Course.

She is the recipient of many awards including the Hammer Award, the Commander’s

Award for Public Service, and the Meritorious Civilian Service award. Dr. Wells is a National

Contract Management Association (NCMA) Fellow and a Certified Professional Contracts

Manager (CPCM). 

Dr. Wells resides in Falls Church, Virginia with her husband, John H. Wells, Ed.D., and

their children, Martha and David.
INTENTIONALLY BLANK.
1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

ATTACHMENT IV

Review of the Department of Defense’s (DoD) Acquisition of

Vaccine Production Memorandum
INTENTIONALLY BLANK.

Enclosure 2

DEPSECDEF Review of the Department’s Acquisition of Vaccine Production

Approach to be Followed

1. Tasks (from DEPSECDEF memo dated July 20, 2000)

a. Consider vaccines—for which DoD is a major customer—to protect service members

from biological warfare threats as well as infectious diseases.

b. Compare DoD status quo with best business practices and identify if/how DoD can

leverage best aspects of private sector programs from industry.

c. Determine whether the DoD program requires acquisition processes unique from normal

departmental acquisition procedures.1

d. Develop recommendations for how the Department should best develop and oversee a

vaccine production program.

2. Participants

a. DoD personnel may serve as technical advisors to the panel; not as panel members.

b. Panel chair with widely recognized expertise in the commercial vaccine industry is the

preferred choice; however, this is not essential if a creditable one is not available.

c. Execute both a disclosure statement of related activities and plans, as well as nondisclosure statements.

3. Approach

a. SAIC prepares read-ahead material for panel members.

b. SAIC identifies candidate presenters from DoD and from industry and defines the scope

of their presentations to include “must address” items.

c. SAIC conducts a critique of all read-ahead documents, and identifies potential issues and

questions for panel consideration.

d. Panel receives read-ahead presentations from DoD with SAIC critiques, then members

meet to discuss, identify issues and additional questions, and arrange schedules for

interviews.

e. Panel members interview “presenters” in a question and answer format.

f. Slip the meeting schedule start until September and adhere to November 20 due date in

the DEPSECDEF memo.

g. Final product is DEPSECDEF briefing and back-up material.

h. Read-ahead material and proceedings will be organized and catalogued for future

reference.

 

1 Operationally defined as DoD Agency and Component augmentation to and implementation of the DoDD 5000

series policies and Goldwater-Nichols Act.
Enclosure 3

DEPSECDEF Review of the Department’s Acquisition of Vaccine Production

Recommended Presentations

The following table contains recommended topics and points to be presented to the panel

assembled in response to the subject. The respondent organizations are offered the opportunity

to expand upon the mandatory key points to be addressed. Additionally, they are requested to

recommend and justify any special policies or procedures they believe are required to facilitate

DoD oversight of successful vaccine procurement. Responses should be in briefing format with

narrative back-up and source references. These should be due to SAIC to initiate a critique not

later than September 6, 2000.

Topic and Key Points to Address

• User Vaccine Policy

• Roles and Responsibilities: RDA from Milestone I to Procurement

• Vaccine Procurement and Logistics 1

• Vaccine Adverse Event Reporting and Product Recall

• Post-marketing Surveillance

• Clinical Record Keeping

• Industrial Base Experience—capacity (surge), stockpile, diversity

• Federal Regulatory Issues

• Vaccine Product Life Cycle Management 2

• Industrial Base Experience

• DoD and Service-unique (if any) Requirements Definition

• Operational Requirements Definition

• Threat Assessments

• Planning, Programming and Budgeting—Resource Management

• Vaccine Acquisition Strategy and Plans—Rationale

• Intellectual Property Management—DoD and Commercial

• Contracting and CRADA Mechanisms

• Product and Operational Liabilities and Indemnification

• Security

• Geopolitical Issues

 

1

 Supplemented by DSPC Representative

2

 Supplemented by DSMC Representative
INTENTIONALLY BLANK.
1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

ATTACHMENT V

Deputy Secretary of Defense Vaccine Acquisition and Procurement Study Panel

Meeting Agenda, September 25 and 26, 2000
INTENTIONALLY BLANK.
DEPUTY SECRETARY OF DEFENSE

VACCINE ACQUISITION AND PROCUREMENT STUDY PANEL MEETING

September 25 and 26, 2000

Crystal Gateway 4

Sign-In Suite 1500

Conference Room on 12th floor

AGENDA

September 25, 2000

8:00 – 8:15 Administrative announcements Dr. Rickett

8:15 – 8:30 Introductions Members and staff

8:30 – 9:30 Background and related studies Dr. Johnson-Winegar

9:30 – 10:00 Discuss approach Dr. Top

10:00 – 10:15 Break

10:15 – 11:00 Threat Assessment Dr. Bancroft

11:00 – 12:00 Requirements & Acquisition Mgmt Dr. Denniston

12:00 – 13:00 Working Lunch – Discussion Panel

13:00 – 13:30 Formal Charge to the Panel Drs. Mark & Clinton

13:30 – 14:30 Acquisition Life Cycle Dr. Rickett

14:30 – 15:30 DoD Vaccine Acquisition Dr. Bancroft

15:30 – 15:45 Break

15:45 – 16:30 DSCP Vaccine Management Mr. McManus

16:30 – 17:00 Discussion of Next Steps Panel

17:00 Recess until 8:00 a.m., September 26th

September 26, 2000

8:00 – 8:15 Administrative announcements Dr. Rickett

8:15 – 9:15 Discuss DoD Vaccine Acquisition Panel

9:15 – 10:15 Industry Best Practices Mr. Gardner

10:15 – 10:30 Break

10:30 – 11:00 DoD Specific Regulatory Issues Mr. Miller

11:00 – 11:30 FDA Regulatory Considerations Dr. Brunswick

11:30 – 13:00 Working Lunch – Clarification Discussions Panel

13:00 – 15:00 Identify Missing Elements Panel

15:00 – 15:30 Break

15:30 – 17:00 Develop Agenda for next meeting Panel

17:00 Recess until next meeting (October 10th?)
INTENTIONALLY BLANK.
1100003

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

ATTACHMENT VI

Deputy Secretary of Defense Vaccine Acquisition and Procurement Study Panel

Meeting Agenda, October 11, 12, and 13, 2000
INTENTIONALLY BLANK.
1000012.doc

DEPUTY SECRETARY OF DEFENSE

VACCINE ACQUISITION AND PROCUREMENT STUDY PANEL MEETING

October 11, 12 and 13, 2000

Epicenter 4A

SAIC Towers

1710 SAIC Drive

McLean, Virginia 22102

Phone: 703-821-4300

Fax: 703-676-4050

AGENDA

October 11, 2000

8:00 – 8:15 Administrative Announcements Dr. Rickett

 8:15 – 9:45 Recap and Discussion Panel

 9:45 – 10:00 Break

10:00 – 11:00 Defense Contract Management Agency Maj Gen Malishenko, USAF

11:00 – 12:00 Program Office/Contracting Interactions Mr. Scott

12:00 – 13:00 Working Lunch – Discussion Panel

13:00 – 15:00 Develop Approach and Questions for Day 2 Panel

15:00 – 15:15 Break

15:15 – 17:00 Develop Approach and Questions for Day 2 Panel

October 12, 2000

 8:00 – 9:00 Interview LTG Kern, U.S. Army Panel

 9:00 – 10:00 Interview MG Parker, U.S. Army and

 Ms. Armbruster, JPO BD Panel

10:00 – 10:15 Break

10:15 – 11:15 Interview COL Hoke, U.S. Army and

 COL Danley, U.S. Army Panel

11:15 – 12:00 Discussions Panel

12:00 – 13:00 Working Lunch – Discuss Way Forward Panel

13:00 – 15:00 Discussions and Report Development Panel

15:00 – 15:15 Break

15:15 – 17:00 Report Preparation Panel

October 13, 2000

8:00 – 10:00 Report Preparation Panel

10:00 – 10:15 Break

10:15 – 12:00 Report Preparation Panel

12:00 – 13:00 Working Lunch – Discussions Panel

13:00 – 15:00 Report Preparation Panel

15:00 – 15:15 Break

15:15 – 17:00 Report Preparation Panel
INTENTIONALLY BLANK.
DoD Acquisition of Vaccine Production Report to the De

by the Inde

1100003 

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

APPENDIX B

Generic Industry Process for Biologics Product Development

WMA 

Preparation

Proof of Efficacy & 

Manufacturability

Dose & Scale 

Definition

Product & Process 

Definition Proof of Concept Preclinical Development 

WMA Preparation Proof of Efficacy & Manufacturability Dose & Scale Definition Product & Process Definition Proof of Concept Preclinical Development

Identify candidate diseasesAnalyze biology of disease to identify potential antigens for a vaccineIdentify and develop in vitro assays to test for immunityDevelop in vitro system for expression for candidate vaccinesOptimize in vitro expression systemConduct biochemical characterization of the antigenIdentify and develop animal model of the disease (if any)Conduct preclinical testing in the animal model(s)Identify a need for adjuvantsStart analyzing alternatives for formulation (excipients and storage conditions)Start stability program based on formulation and storage conditions

Marketing

Statement of Interest (SOI)

Clinical/Regulatory

SubmitIND

Proof of ConceptClinicals

Product, Process and Formulation Development

ProcessAnalytical Assays

Validate Potency, Safety & Ster. Assay

ID Parameter for POC Clinicals

Anal. & Process Plan

Serology AssaysPackaging & Stability

Early Research Stability Experiments

Facilities

Manufacturing Feasibility Studies

Supply/Production

Prepare LabLots for POCClinicals

Marketing Needs Report

Process Assessment Clinicals

Validate Raw Material, Stability and Release Assay 

Product, Process & Formulation Finalized 

Spec. Strategy & RationaleDevelop & Evaluate High Throughput Serology Assay 

Probe & Clinical Lot Stability Studies

Preliminary Product & Packaging Definition 

Economic Feasibility Assessment

Dose Ranging Studies

Dose DefinedScale Defined

Validate In-Process and Product Characterization Assays

Update Spec. Strategy & Rationale

Kit Vendor Development of Serology Assays Capable of Evaluation PPost-Disease Seroconversion

Pilot Lot Stability Studies

Filling and Packaging Development

Mfg.Strategy

Prepare Prelim. Eng. & Basis of Design

Prepare Pilot Lots for POC Clinicals

Pre-Launch Strategy

Efficacy Studies

Consistency Studies

Transfer Assays

Update Spec. Strategy & Rationale

Final Product & Primary Package Definition

Market Container Stability Studies

Build and Validate Facility

Prepare Phase 3 Quality Lots

Prepare Consistency Lots

Prepare WMA

Update Spec. Strategy & Rationale

Full Scale Lot Stability Studies

Final Product & Packaging Definition

Prepare Launch Quantit

Regulatory Assessment

Detail Design

Proof of Concept Bridging Studies
INTENTIONALLY BLANK.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 C-1

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

APPENDIX C

Several Categories of Consideration for Vaccine Discovery

through the Manufacturing Process

3⁄4 Technologies

- Conventional – live attenuated or inactivated organisms

- DNA

- Recombinant proteins

- Viral or bacterial vector delivery

- Immune stimulators

- Synthetic peptides

- Fermentation

- Cell culture

- Inactivation

- Protein purification

- Polysaccharide purification

- Protein-polysaccharide conjugation

- Adjuvant adsorption

- Lyophilization

3⁄4 Source Materials

- Vendor audits

- Source identifiers

- Lot traceability

- Process control

- Quality control

- Material specifications

- Inspection

- Container testing

3⁄4 Specialized Equipment

- Fermenters

- Robots

- Centrifuges

- Filtration Systems

- Chromatography systems

- Lyophilizers

- Filling systems

- Inspection systems

- Packaging systems

- Automation

3⁄4 Product Characterization

- Capillary zone electrophoresis

- DNA and protein sequencing

- Enzyme immunoassay and radioimmunoassays

- HPLC

- NMR

- Immunochemical rate nephelometry

- Size exclusion chromatography
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 C-2

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

Several Categories of Consideration for Vaccine Discovery

through the Manufacturing Process (cont.)

3⁄4 Personnel Qualifications and Training

- 30%–40% Advanced Degrees in area directly related to job

o Technology (e.g., immunology and virology)

o Process engineering and manufacturing (e.g., biologicals)

o Regulatory (e.g., FDA, Environmental Protection Agency, and

Occupational Safety and Health Administration)

o Business (e.g., management, processes, and cost analysis)

- Training (2–3 weeks per year)

o Cutting edge technology, technology transfer, and analytical

methodologies

o Process specifics and manufacturing support

o current Good Manufacturing Practice, current Good Clinical Practice,

and current Good Laboratory Practice

o Project planning (cost, schedule, and performance)

3⁄4 Quality

- Assurance (e.g., internal audits, regulatory updates, and agency inspections)

- Testing

- Validation (e.g., equipment cleaning, sterilization, and performance)

- Product release [sequential and repeated testing (e.g., raw materials → test

→ culture media → test → bulk intermediates → test → final formulated

bulk → test & CBER release → filled containers → test → packaged items

→ test → release to market) throughout process with detailed documentation

to support release by CBER]. Note: With regard to product release, it

typically takes 7 to 12 months to get bulk material released and 6 to 12

weeks for release approval following filling.

- Licensing

- Environmental monitoring
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 D-1

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

APPENDIX D

Briefing – DoD Acquisition of Vaccine Production (Report to the Deputy Secretary of

Defense by the Independent Panel of Experts), November 29, 2000
INTENTIONALLY BLANK.
DoD Acquisition of Vaccine 

Production

vember 29, 2000

ort to the Deputy Secretary of Defense

y the Independent Panel of Experts
2

Panel

lin H. Top, Jr., M.D. – Chair

ve Vice President and Medical Director

mune, Inc.

J. Dingerdissen

Director, Viral Vaccine Manufacturing

& Co., Inc.

am H. Habig, Ph.D.

, R&D Quality Assurance

r, Inc.

d V. Quinnan, Jr., M.D.

r, Preventive Medicine, Medicine and Microbiology

ed Services University of the Health Sciences

L. Wells, Ph.D.

Executive Director

tee for Purchase from People Who are Blind or Severely Disabled
3

Terms of Reference

uty Secretary of Defense requested that the study by the

endent panel of experts focus on the following areas:

nes to protect Service members against biological warfare threats as 

 infectious diseases.

parison of current Department efforts with best business practices 

biologics industry, and if/how the Department can leverage the best 

s of the private sector programs from industry.

rmination of whether the DoD program requires acquisition 

ses unique from normal departmental acquisition procedures. 

velopment of recommendations for how the Department should

velop and oversee a vaccine acquisition production program.
4

Facts Bearing on the Problem

and endemic diseases are proven, high 

equence threats to military operational 

tiveness

ines are lowest risk, most effective protection

tter than antibiotics or other treatments

able force projection

ent approach is insufficient and will fail

EW APPROACH CAN MAKE THIS PROGRAM

RK
5

hy Will Current Program Fail?

roach is contrary to business success model

o one in charge

iffuse management

agmented program

k of integration from discovery through 

nsure

k of essential scientific oversight and talent 

fficient capture of industrial base

ls and dollars do not match
Industry Best Practices

6
7

uccessful Vaccine Acquisition

ry Best Practices effectively integrate:

cy

duct life cycle

esearch

evelopment

oduction

censure

ustainment

ources 

agement
8

ding stability 

front multiyear commitment

ible “reprogramming” authority ($ and type)

duct focus, not budget focus

Resources

Industry Benchmark

Baseline Schedule Fully Funded
9

D $300M - $400M/product

lity capital investment estimate

oduction, labs, and support -

5M - $115M/product 

rations and Maintenance Estimate

anufacturing $30M - $35M/product/year

DoD Products Underresourced

Resources (cont.)

Industry Benchmark
10

0 people

eptional and specialized skills

ce national pool

mpetitive compensation

cial HR programs necessary

ecruit, train, and retain

People + Process → Vaccines

Human Investment

Industry Benchmark at 8 Product Scale
11

l is quality product 

ntific expertise at every level

lem focus for continuing improvement

apid assessment and decisions

itigate risk at every stage

owered and accountable management 

ms

Management

Industry Benchmark
DoD Practices

12
13

Best Business Assessment

st Practices Assessment of DoD Rationale for Assessment

covery

nsure Piecemeal process

nt Good S&T, inadequate development and production

alifications of

Vaccine Acquisition ≠ Weapons System Acquisition

Focus and

y Fragmented and Multilayered below DEPSECDEF

lity Annual allocation and frequent decrement drills

mitment Development/Acquisition not funded following discovery

ogramming Limited by Congress

duct Quality Goal ; Execution

R

R

G R Y

R

R/YR/Y

R/Y

ull Compliance

Moderate Compliance

ow Compliance

No Compliance (High Risk)

Y
14

Strategic Options

stry

ernment

mbined integrated approach
15

ndustry Option: Impediments

 & scope of program

strial base at full capacity

manufacturing

 to industry

fficacy risk

ogram stability

erceptions

olitical

ense procurement practices
16

vernment Option: Impediments

 - 2,500 personnel

k of personnel experienced in vaccine 

lopment processes

competitive recruitment
17

erred Option: Integrated Approach

bines:

nagement/development skills of industry

quisition skills of DoD

entists from Federal, academic/industry labs

ploit industry development/manufacture where 

sible

CO for development/manufacture of remaining 

ducts

Incentivize Industry
18

posed Management Organization

PM PM

trategic Board VARC DMRC

echnical Board

erformers Labs GOCO

PM

Industry

UniversitiesUSD(AT&L)

PEO

VAE
19

/buildout to process and manufacturing scale

ndable

 product/process capacity

production/scale-up

roducts at one time

ent clinical, regulatory, QC & QA elements, 

ed research lab capability

ersity/industry corridor location is essential--

heast coast lowest risk

GOCO Facilities
20

Resource Estimates

(8 Vaccines*)

D Funds -- $3.2B

al Capital Funding ≥ $370M

5M - $115M for each additional vaccine after 

st 4

% - 10% infrastructure improvement/year

rations and Maintenance ~ $300M/year

0 people

 MIDRP require >8 vaccines total; study scale was 8 vaccines
21

Industry Incentives

rture to industry

ourage industry development of vaccines

ongest multiyear contracts possible

centive-based contracts

overnment-provided facility
22

ndings and Recommendations

cines to protect Service members against 

ogical warfare threats as well as infectious 

ases.

ombine programs from discovery to production
23

indings and Recommendations (cont.)

mparison of current Department efforts with best 

ness practices in the biologics industry, and if/how 

Department can leverage the best aspects of the 

ate sector programs from industry.

urrent Department efforts do not meet industry best practices:

Diffuse management and fragmented lines of responsibilityInadequate scientific oversightInadequate program integration from discovery through licensureInadequate resources to meet goals

dopt integrated approach utilizing:

Management/development skills of industryAccountable, lean DoD management structureStrong technical guidance and personnelGOCO
24

etermination of whether the DoD program 

ires acquisition processes unique from 

mal departmental acquisition procedures.

es, vaccine acquisition is different from weapons 

quisition and success requires different procedures

Strong technical input imperative

– Workforce– Management

Stable, long-range funding for vaccine life cycleReprogramming authority

indings and Recommendations (cont.)
25

e development of recommendations for 

w the Department should best develop and 

ersee a vaccine acquisition production 

gram.

Combined, integrated model

Focused and streamlined organization 

Segregated, OSD-sponsored funding 

Incentivized industry involvement (with GOCO)

DoD, Executive Branch, and Congressional support 

to remove impediments and provide necessary incentives

indings and Recommendations (cont.)
Backup Slides

26
27

onent Example

ch Follow-on candidates

pment Optimal shot regimen

tion Validated process

ure FDA compliance

ment Reliable supply

roduct Life Cycle Integration
28

Success

ntifically competent, empowered management

t integrate

cience & technology

DiscoveryApplied activities

oduct development

anufacturing

oduct licensure

ostlicensure sustainment
29

Management Organization

CJCS

CSA

DCSOPS

CG, TRADOC

CG, AMEDD C&S

TSG

MAMP

JROC

ASD(HA)

ASA(MR&A)

TSG

USD(PR)

MRSP

USD(AT)

DAE

DR&E

 Life Sciences

ATSD(NCB)

Dep, Counterproliferation

ASA(RDA)

AAE

DAS-R&T

CG, USAMRMC

SECDEF

DEPSECDEF

CINCs

JNBC 

Defense Board

JSMG -- JSIG

e

ASTMP

DAB

MAISRC

ASRC

AMAISRC

MEDSYS

MDA

MARP

AMP

TFSC

CJCS

CSA

DCSOPS

CG, TRADOC

CG, AMEDD C&S

TSG

MAMP

JROC

ASD(HA)

ASA(M&RA)

TSG

USD(PR)

MRSP

REQUIREMENTS

USD(AT&L)

DAE

DR&E

SD(S&T)

ATSD(NCB)

DATSD(CBD)

ASA(ALT)

AAE

DAS-R&T

CG, USAMRMC

SECDEF

DEPSECDEF

CINCs

JNBC 

Defense Board

JSMG -- JSIG

e

ASTMP

DAB

MAISRC

ASARC

AMAISRC

MEDSYS

MDA

MARP

AMP

TFSC

ACQUISITION
30

DATSD (CP/CBD)• Issues BES preparation instructions• Issues funds suballocation instructions• Approves BES and Budget Allocation 

Instructions

• Submits BES/PB• Approves reprogramming actions• Oversees program execution

• POM/BES/PB• Funds Distribution Information• Execution Reports• Reprogramming 

Recommendations

• BES/PBD Documentation• Reprogramming Recommendation

• BES/PB Inputs• Execution Reports

MIPR/ 

ballocations

ES/PB

structions

Budgeting

llocates Funds IAW PB 

A/FM)

dinates/Approves 

ogramming actions (DTRA/CB)

tors program execution

g Agencies

bute Funds to performers

pate in POM/BES/PB 

ration

t program execution

gram within Service allocation

st reprogramming authority

ers

ute programs

rt execution status

re BES/PB inputs

JSMG

• Distributes POM/BES/PB guidance• Consolidates POM/BES/PB inputs and resolves 

Issues

• Prepares/updates POM/BES/PB documentation• Coordinates funding adjustments• Makes reprogramming recommendations• Maintains supporting database

JNBCDB Secretariat

• Prepares BES/PB in coord with JSMG• Reviews and analyzes program execution• Prepares funds distribution information• Makes reprogramming recommendations• Reports execution status to DATSD 

(CP/CBD)

• Updates database

JSMG Hand Book of Standard Operating Procedures, Fig IV-I, Page 19 

Database Updates

BES/PB Submission

• Budget Suballocation 

Instructions

• Reprogramming 

Instructions

Appropriation

$ - Funding Document

$ - PBAS Execution Reports

Execution Reports

BES/PB Instructions

• POM/BES/PB• Reprogramming 

Requests

• BES/PB 

Instructions

POM/BES/PBInstructions

gress

D Comptroller

...

mical and Biological Defense Program

Funds Management Process
31

oposed Management Structure

ored Acquisition Model

SD Vaccine Acquisition Executive (VAE)

versight (ACAT I)--technically qualified

rategic Board advises VAE

cine Acquisition Review Council (VARC) 

Defense Medical Requirements Council 

MRC)
32

t Program Executive Officer (PEO)

AE and PEO with scientific and acquisition skills

ntific & technical advisors on tactical 

ations to PEO

eriodic (scheduled) review

 responsible for sponsoring ($) S&T/relevant 

structure and exploits DoD lab capability

dual hats

oposed Management Structure
33

Resource Estimates

D Funds -- $3.2B

successful vaccines (7-12 years each)*

00 - $400M/product R&D to licensure

2 products/year to start4 products/year at year 48 products/year when mature

 MIDRP require >8 vaccines total; study scale was 8 vaccines
34

tal funds >$370M

00M construction for manufacturing

70M construction for labs

5-$115M for each additional vaccine after the 

itial 4

%-10% infrastructure improvements/year at year 8

rations and Maintenance funds

00M/year for 8 vaccines

Resource Estimates (cont.)
35

0 people–exceptional and specialized skills

carce national pool

mpetitive compensation

cial programs necessary

ain to expand the pool

ecruit

etain

ompensate

People + Process → Vaccine

Human Investment Estimate
Vaccine Study Panel

36
37

Panel Sponsors

s Mark, Ph.D.

ctor, Defense Research and Engineering

rrett Clinton, M.D., M.P.H.

ng Assistant Secretary of Defense (Health Affairs)
38

Panel Support

ment of Defense

Johnson-Winegar, Ph.D.

Assistant to the Secretary of Defense (Chemical/Biological Defense)

t E. Foster, Ph.D.

, Bio Systems, Office of the Deputy Under Secretary of Defense (S&T)

McManus

, Pharmaceuticals Group, Defense Supply Center, Philadelphia

ce Applications International Corporation

. Rickett, Ph.D. Joseph C. Denniston, V.M.D., Ph.D. 

 H. Bancroft, M.D. Mark. R. Brunswick, Ph.D.

L. Bareis, Ph.D. James M. Miller, Esq.

n D. Gardner, C.C.E/A. Joseph F. Soukup, Ph.D.

 Associates, Inc.

T. Singley, III
39

Briefings

D(CBD): Background and Related Issues

U.S. and International Vaccine Industrial Base Vaccine Manufacturing Industry Best PracticesFood and Drug Administration ConsiderationsOverview of DoD Requirements Related to VaccineProduction Selected Examples of DoD Experience withAcquisition of Licensed Vaccines Worldwide Biological Warfare Threat

C: Requirements Generation Process and Acquisition Life

Cycle 

C: Defense Acquisition Process Milestones and Phases: 

A Summary of the Revised 5000 Series
40

Briefings (cont.)

 Defense Acquisition Workforce

Vaccine Acquisition Program: Acquisition of Biological 

se Vaccines

Army Medical Research and Materiel Command: Vaccine 

opment and Production Process & Issues

se Supply Center Philadelphia: Vaccine Management

se Advanced Research Projects Agency: Vaccine 

am Overview

quarters, U.S. Navy: Review of DoD Acquisition and 

ction of Vaccines
41

Interviews

nant General Paul Kern, USA, Military Deputy to the 

ant Secretary of the Army (AL&T) and Director, Acquisition

 Management

 General Timothy Malishenko, USAF, Director, Defense 

act Management Agency

obert Scott, Senior Principal, American Management Systems

 General John Parker, M.D., USA, Commanding General, U.S. 

Medical Research and Materiel Command (USAMRMC)

Vicky Armbruster, Joint Program Manager for Biological 

se

el David Danley, Ph.D., USA, Project Manager, Joint Vaccine

sition Program

el Charles Hoke, M.D., USA, Director, Military Infectious 

es Research Program, HQ, USAMRMC
42

Acronyms

cquisition Category

rmy Acquisition Executive

rmy Medical Department Center and School

rmy Modernization Plan

ssistant Secretary of the Army for Acquisition, 

ogistics and Technology

ssistant Secretary of the Army for Manpower 

d Reserve Affairs

rmy Systems Acquisition Review Council

ssistant Secretary Defense for Health Affairs

rmy Science and Technology Master Planssistant to the Secretary of Defense (Nuclear, 

hemical, Biological)

ological Defense

udget Estimate Submission

ological Warfare

ommanding General

ommander in Chief

hairman, Joint Chiefs of Staff

CSA Chief of Staff, ArmyDAB Defense Acquisition BoardDAE Defense Acquisition ExecutiveDATSD(CBD) Deputy Assistant to the Secretary of 

Defense (Chemical/Biological Defense)

DCSOPS Deputy Chief of Staff for Operations

(U.S. Army)

DDR&E Director, Defense Research and 

Engineering

DEPSECDEF Deputy Secretary of DefenseDIA Defense Intelligence AgencyDMRC Defense Medical Requirements CouncilDoD Department of DefenseDTAP Defense Technology Area PlanDTRA Defense Threat Reduction AgencyDUSD(S&T) Deputy Under Secretary of Defense 

(Science and Technology)

FDA Food and Drug AdministrationGOCO Government-Owned, Contractor-Operated
43

Acronyms (cont.)

int Nuclear, Biological, Chemicalint Nuclear, Biological, and Chemical 

efense Board

int Requirements Oversight Councilint Services Integration Groupint Services Materiel Groupint Technology Coordinating Groupint Warfighting Science and Technology Plan

ajor Automated Information System Review 

ouncil

ission Area Materiel Plan

anagement Assessment Review Plan

ilestone Decision Authority

ilitary Infectious Diseases Research Program

ilitary Interagency Purchase Request

edical Readiness Strategic Plan

ffice of Secretary of Defense

esident's Budget

ogram Budget Accounting System

ogram Executive Officer

PM Program ManagerQA Quality AssuranceQC Quality Control R&D Research and DevelopmentRDA Research, Development, and AcquisitionS&T Science & Technology SAIC Science Applications International 

Corporation

SECDEF Secretary of DefenseTFSC Theater Functional Steering CommitteeTRADOC Training and Doctrine CommandTSG The Surgeon GeneralUSAMRMC U.S. Army Medical Research and 

Materiel Command

USD(AT&L) Under Secretary of Defense for 

Acquisition, Technology and Logistics

USD(PR) Under Secretary of Defense for Personnel 

and Readiness

VAE Vaccine Acquisition ExecutiveVARC Vaccine Acquisition Review Council
INTENTIONALLY BLANK.
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 E-1

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

APPENDIX E

Acronyms

ACAT Acquisition Category

AAE Army Acquisition Executive

ACIP Advisory Committee on Immunization Practices

AMAISRC Army Major Automated Information System Review Council

AMEDD C&S Army Medical Department Center and School

AMP Army Modernization Plan

ASA(ALT) Assistant Secretary of the Army for Acquisition, Logistics and Technology

ASA(M&RA) Assistant Secretary of the Army for Manpower and Reserve Affairs

ASARC Army Systems Acquisition Review Council

ASBREM Armed Services Biomedical Research Evaluation and Management (Committee)

ASD(HA) Assistant Secretary Defense for Health Affairs

ASTMP Army Science and Technology Master Plan

ATSD(NCB) Assistant to the Secretary of Defense (Nuclear, Chemical, Biological)

AVA Anthrax Vaccine, Adsorbed

AVP Acquisition of Vaccine Production

BDP Biological Defense Program

BES Budget Estimate Submission

BW Biological Warfare

CBER Center for Biologics Evaluation and Research

CG Commanding General

CINC Commander in Chief

CJCS Chairman, Joint Chiefs of Staff

CSA Chief of Staff, Army

DAB Defense Acquisition Board

DAE Defense Acquisition Executive

DAS-R&T Deputy Assistant Secretary of the Army for Research and Technology

DATSD(CBD) Deputy Assistant to the Secretary of Defense (Chemical/Biological Defense)

DCSOPS Deputy Chief of Staff for Operations (U.S. Army)

DDR&E Director, Defense Research and Engineering

DEPSECDEF Deputy Secretary of Defense

DIA Defense Intelligence Agency

DLA Defense Logistics Agency

DMRC Defense Medical Requirements Council

DNA Deoxyribonucleic Acid

DoD Department of Defense

DTAP Defense Technology Area Plan
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 E-2

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

DTRA Defense Threat Reduction Agency

DUSD(S&T) Deputy Under Secretary of Defense (Science and Technology)

EEE Eastern Equine Encephalitis

FDA Food and Drug Administration

FTE Full-time Equivalent

GOCO Government-Owned, Contractor-Operated

HIV Human Immunodeficiency Virus

IAW In Accordance With

IDP Infectious Disease Program

IND Investigational New Drug

IOM Institute of Medicine

JNBC Joint Nuclear, Biological, Chemical

JNBCDB Joint Nuclear, Biological, and Chemical Defense Board

JPO BD Joint Program Office for Biological Defense

JROC Joint Requirements Oversight Council

JSIG Joint Services Integration Group

JSMG Joint Services Materiel Group

JTCG Joint Technology Coordinating Group

JVAP Joint Vaccine Acquisition Program

JVAP PMO Joint Vaccine Acquisition Program, Project Management Office

JWSTP Joint Warfighting Science and Technology Plan

MACOMs Major Commands

MAISRC Major Automated Information System Review Council

MAMP Mission Area Materiel Plan

MARP Management Assessment Review Plan

MDA Milestone Decision Authority

MIDRP Military Infectious Diseases Research Program

MIPR Military Interagency Purchase Request

MRSP Medical Readiness Strategic Plan

NCI National Cancer Institute

NEPA National Environmental Policy Act

NIAID National Institute of Allergy and Infectious Diseases

O&M Operations and Maintenance

ODDR&E Office of the Director, Defense Research and Engineering

OMA Operations and Maintenance, Army

OSD Office of Secretary of Defense

OTA Other Transaction Authority

PB President’s Budget

PBAS Program Budget Accounting System

PBD Program Budget Decision

PEO Program Executive Officer
DoD Acquisition of Vaccine Production Report to the Deputy Secretary of Defense

by the Independent Panel of Experts

1100003 E-3

This document reflects the independent opinions of the Vaccine Study Panel

and should not be construed as the official position of the DoD.

PMs Program Managers

PPB Planning, Programming, and Budgeting

PSC Prime Systems Contractor

QA Quality Assurance

QC Quality Control

R&D Research and Development

RDA Research, Development, and Acquisition

RDT&E Research, Development, Test, and Evaluation

RFPs Request for Proposals

S&E Scientists & Engineers

S&T Science & Technology

SAIC Science Applications International Corporation

SEB Staphylococcal Enterotoxin B

SECDEF Secretary of Defense

TFSC Theater Functional Steering Committee

TRADOC Training and Doctrine Command

TSG The Surgeon General

UNICEF United Nations International Children’s Emergency Fund

USAMRIID U.S. Army Medical Research Institute of Infectious Diseases

USAMRMC U.S. Army Medical Research and Materiel Command

USD(AT&L) Under Secretary of Defense for Acquisition, Technology and Logistics

USD(PR) Under Secretary of Defense for Personnel and Readiness

VAE Vaccine Acquisition Executive

VARC Vaccine Acquisition Review Council

VEE Venezuelan Equine Encephalitis

WEE Western Equine Encephalitis

WMA Worldwide Marketing Assessment

WRAIR Walter Reed Army Institute of Research
INTENTIONALLY BLANK.

INTENTIONALLY BLANK.