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**National Vaccine Advisory Committee (NVAC)**

**February 3-4, 2004 meeting**

[Meeting Overview]{.underline}

The major focus of this meeting was the 2003 influenza epidemic.
Presentations included those by senior personnel of the Centers for
Disease Control and Prevention, and representatives of the vaccine
manufacturers, insurers and the Center for Medicare and Medicaid
Services (CMS). The three subcommittees in their respective meetings
also discussed influenza from their perspectives of immunization
coverage, communication and future vaccines. Dr. Beato requested that
NVAC examine the Nation's influenza system and prepare a report with
recommendations for the Department.

[Committee Members in Attendance]{.underline}

Dr. Georges Peter---*Chair*

Dr. Ann Margaret Arvin

Dr. Jeffrey P. Davis

Dr. Patricia Fast

Dr. Fernando A. Guerra

Dr. Charles M. Helms

Dr. Alan Richard Hinman

Ruth Katz

Dr. Jerome O. Klein

Mary Beth Koslap-Petraco

Dr. Bruce Gellin (Executive Secretary)

*Liaison Representatives*

Dr. Steven Black

Dr. Patricia N. Whitley-Williams

Dr. Donald E. Williamson

Ms. Jackie Noyes - AACV

Dr. Gary D. Overturf -- VRBPAC

*Ex Officio Members*

Dr. Norman Baylor, Microbiologist, Center for Biologics Evaluation and
Research (CBER), Food and Drug Administration (FDA)

Dr. Steve Cochi, Acting Director, National Immunization Program (NIP),
Centers for Disease Control and Prevention (CDC)

Dr. George Curlin, Division of Microbiology and Infectious Diseases,
National Institute of Allergy and Infectious Diseases, NIH

Col. Renata J. M. Engler, Chief, Allergy/Immunology Department, Walter
Reed Medical Center, Department of Defense (DoD)

Dr. Geoffrey Evans, Medical Director, Division of Vaccine Injury
Compensation Program, Health Resources and Services Administration
(HRSA)

Dr. James Randolph Farris, Regional Administrator, Region VI, Centers
for Medicare and Medicaid Services (CMS)

Emily Marcus Levine, Senior Attorney, Office of the General Counsel,
DHHS

*Committee Members Absent*

Neal Brandes, U.S. Agency for International Development (USAID)

Dr. Myron Levin, Chair, Advisory Committee on Immunization Practices
(ACIP)

Dr. William Schaffner, Professor and Chair, Department of Preventive
Medicine, Vanderbilt School of Medicine

**Welcome from Chair**

Dr. Peter welcomed the meeting attendees asked NVAC members to introduce
themselves. He explained that Dr. Schaffner could not attend the meeting
for personal reasons. NVAC has two unfilled positions that Dr. Gellin is
working to fill, but new liaison and ex officio members have joined the
committee, including Dr. Overturf and Dr. Levin. He welcomed Dr. Cochi,
the new Acting Director of NIP, and noted that Dr. Walt Orenstein, the
program's previous director, was also in attendance. He introduced Dr.
Baylor as the new CBER representative and Dr. Farris as the new CMS
representative and noted that Dr. Brandes is the new USAID
representative. Dr. Peter then asked all of the guests in the audience
to introduce themselves.Dr. Peter asked NVAC members to declare
conflicts of interest as they arise, noting that they rarely occur given
the general issues they discuss.

**Welcome from the Acting Assistant Secretary for Health - Dr. Cristina
Beato**

Dr. Beato welcomed meeting attendees and expressed her appreciation for
NVAC. She acknowledged the critical work NVAC does for DHHS and the
nation. She explained that DHHS is the largest department in the federal
government, noting that the budget is over \$120 billion more than the
DOD's.

*[Budget Overview]{.underline}*

Dr. Beato provided an overview of the President's budget for FY 2005 for
vaccines and immunizations. The President has requested \$1.5 billion
for the Vaccines for Children (VFC) program and a series of improvements
in financing childhood vaccines. The proposed budget would improve
access to VFC vaccines for uninsured children entitled to these vaccines
and enable underinsured children to be vaccinated at state and local
public health departments. All VFC children would have record access to
all new and improved vaccines. Access to pneumococcal conjugate vaccine
for these children has been unsteady. The proposed budget restores
tetanus and diphtheria toxoid vaccines to the VFC program and repeals
the price caps that have excluded them from the program. The private
sector price is \$7.91 and VFC is capped at \$.32 per dose. DHHS is
building a national stockpile of childhood vaccines in preparation for
part of the Bioterrorism Program in Public Health Preparedness. An
investment of \$751 million will be made between FY03 and FY06 to build
a vendor-managed, 6-month supply of all childhood vaccines by 2006. Dr.
Beato highlighted the inclusion of approximately \$73 million for the
influenza vaccine in the VFC Program. There is a routine purchase of
\$33 million for children at high risk for complications of influenza:
children aged 6 to 23 months and aged 2 to 18 years with medical
conditions that put them at risk for influenza complications. The
proposal also includes \$40 million for the 2004--2005 influenza season
and \$40 million for the 2005--2006 season. Vaccines would be stockpiled
to meet exceptional demand for each season. Furthermore, DHHS is seeking
to increase the \$50 million investment in 2004 with a \$100 million
investment in 2005 to enhance our capacity to respond to an influenza
pandemic. These funds would accelerate the development of cell culture
influenza vaccine and provide year round availability of raw materials
needed to produce egg-based vaccines until the cell culture technology
is ready. She noted that the President is very committed and that the
Secretary has been in the forefront of influenza preparation issues.

*[Request for NVAC Assessment of Influenza System]{.underline}*

Dr. Beato asked that NVAC take a step back and critically look at the
current national influenza program as a whole to see if it is still on
track. She noted that the current system is very complex and every day a
new facet comes up. The meeting agenda allows NVAC to hear from DHHS
agencies, vaccine manufacturers, and other key stakeholders. She asked
the committee to consult with NVPO, the agencies within DHHS, and their
advisory committees, as appropriate, to thoroughly review the national
influenza program and report their insights and recommendations. She
acknowledged that this is a big task and requires assistance from the
national principal advisory committee.

**Overview of NVPO - Dr. Gellin**

Dr. Gellin then provided a "preface" to today's meeting. He noted that
the message is finally out about the seriousness of influenza as a
disease. The season started early this year, and the media highlighted
children's deaths, which helped reinforce the concern about influenza
and what it is. Headlines about vaccine shortages appeared around the
release of the CDC influenza-like illnesses study. He noted however that
when we look the entire population of 185 million, we still fall short
in broad coverage; the US demand is only about 50% to 60% of this number
every year.

As Dr. Beato discussed, Dr. Gellin explained the need to look at how the
situation can be improved. With regard to the budget, from his
perspective, Dr. Gellin wanted to underscore the issue of pandemic
influenza preparedness and exploring other approaches to producing
influenza vaccines, noting that two pre-solicitations had been announced
on FedBizOpps

Influenza 2003--2004: Review and Lessons Learned for Next Year and the
Future

T**he Current Season: Virus/Disease/Vaccine and Efficacy - Dr. Nancy
Cox**

Dr. Cox discussed the influenza disease that occurred last year by
examining national morbidity and mortality data, the disease compared
with other influenza seasons, mortality in children, and the circulating
viruses. Influenza received a lot of attention in the 2003--2004 season
from the media and others. This attention was caused by four factors:

Sustained increases in influenza activity were reported unusually early.

Influenza-related pediatric deaths were prominently reported by the
national media.

Vaccine manufacturers had sold all vaccines by mid-December as demand
continued.

A less than optimal match between the predominant circulating viruses
(A/Fujian/411/02-like) and the corresponding vaccine component
(A/Panama/2007/99).

She provided an overview of the season's virologic surveillance, which
is based on the number of isolates collected by collaborating
laboratories. The majority of the viruses were influenza A viruses, and
for those that were subtyped, 99% were Influenza A H3N2 viruses. She
then showed a graph representing the percentage of respiratory specimens
testing positive for influenza by week. She compared the 2003--2004
season data to the 1999--2000 and 2002--2003 seasons to show how much
earlier it occurred. The 1999--2000 season was the last large influenza
A H3N2 epidemic in the U.S., and 2002--2003 season was a relatively
milder season. Dr. Cox reviewed the percentage of visits from
influenza-like illness for the same seasons based on reports by sentinel
providers. The 2003--2004 season began early, had a rapid rise, and
peaked and finished earlier than the 1999--2000 and 2002--2003 seasons.
Again, she noted how much milder the 2002--2003 season was in comparison
to the H3N2 seasons. Dr. Cox showed the pneumonia and influenza
mortality data for 122 U.S. cities from 2000 to the week ending January
24, 2004. There was a substantial peak in mortality this season, which
is now declining. This peak, however, was not as high as the 1999--2000
season, which reached approximately 11.3% of deaths. In addition, she
noted that influenza death rates first rose above the "epidemic
threshold" during week 51 and remained there for five consecutive weeks;
the highest influenza-like illness attack rates were among children and
young adults.

Dr. Cox then discussed influenza-associated deaths among children under
18 years of age. To date, there have been 121 lab-confirmed,
influenza-associated deaths reported to CDC. The age of these children
ranged from 2 weeks to 17 years, with a median age of 3.8 years. Of
these children, 72 (60%) were under 5 years old, and 33 (27%) were aged
6 to 23 months. There were 26 (21%) children who had underlying medical
conditions. Although the CDC does not have complete vaccination records
for these children, for the 57 children with available records, only two
were vaccinated according to recommendations. She noted that the
estimates of vaccine effectiveness for the 2003--2004 season are still
unknown. NIP/CDC conducted a study among healthcare workers in a Denver,
Colorado hospital, but the endpoint to the study was vaccine
effectiveness against influenza-like illness---not against the more
specific endpoint of laboratory-confirmed influenza. The endpoint was
also not vaccine effectiveness against more serious outcomes, such as
hospitalization or death, which would have been too rare in this
population. This study was unable to demonstrate vaccine effectiveness.
Other studies are being undertaken in the U.S. and will be announced
when the results become available. Though she has not reviewed the
methodology, there was a study reported in France that estimated that
vaccine effectiveness was 60% for this past season.

**Vaccine Strain Selection Process and Regulatory Issues - Dr. Jerry P.
Weir**

Dr. Weir reviewed the influenza vaccines that are licensed in the U.S.:

A trivalent inactivated influenza vaccine produced by Aventis Pasteur,
Inc. and Evans Vaccines Ltd. For the 2003--2004 season, production is
estimated at 83 million doses.

A live attenuated influenza vaccine produced by MedImmune Vaccines Inc.
was licensed in June 2003. This is a cold-adapted, intranasal vaccine,
and approximately 4 million doses were produced for the 2003--2004
season.

Dr. Weir then shared a schematic of the timeline for vaccine production
and use. The Northern hemisphere vaccine is issued in the fall from
September to late December or early January. The support and the
preparation work for the vaccine, however, occur throughout the year.
Surveillance is done globally year round, and they monitor for new and
predominant strains. There are constantly new reference strains and
reagents that are being updated. He added that the recommendations are
made at different times of the year for the Northern and Southern
Hemispheres and that recommendations would be made over the next several
weeks for the 2004--2005 season.

Dr. Weir then reviewed the strain selection process. He explained that
vaccine efficacy depends on the vaccine's immunogenicity (potency) and
the match of vaccine with wild-type viruses that are in circulation.
Strain selection is necessary because the antigenic shift of influenza A
and B viruses is continuous. Dr. Weir explained that there are questions
that everyone involved must ask every year for strain selection. These
questions are generally examined in January and February of each year,
are:

Are new (drifted or shifted) influenza viruses present?

Are these new viruses spreading in people?

Do current vaccines induce antibodies against the new viruses (with a
focus on HA)?

Are strains suitable for vaccines available?

Based on these questions, Dr. Weir described the context for strain
selection for the 2003--2004 season. There were no new strains present
for influenza A/H1N1 or for influenza B. He noted that there were new
strains for influenza A/H3N2, although the HA of most strains were
similar to the current vaccine strain. However, a proportion of the
strain, approximately 10% to 20% , was antigenically different. He noted
that these virus isolates had signature amino acid changes that
suggested a potential emerging variant cluster. New influenza A/H3N2
viruses were spreading. New variants, now termed A/Fujian-like, were
found in Asia, Europe, and North America. They were first identified in
late January and late February 2003. For the third question, influenza
A/H3N2 viruses were only partially inhibited by the current vaccines.
The majority of the strains was A/Panama/2007/99-like and well
inhibited; for the A/Fujian-like strains, some were well inhibited while
others were poorly inhibited. These data did not provide a clear picture
of what to do with strain selection.

For the final strain selection question, there were no suitable strains
available for manufacture last winter, because of timing. The first H3N2
variants were identified in February 2003, and there were no H3N2
variant egg isolates until April 2003. High growth reassortants were not
available in June 2003. Dr. Weir noted that manufacturing depends on the
egg-adapted strain and the selected virus strain must grow well for
production.

The vaccine composition for the 2003--2004 season was based on data
available in early March 2003. Both WHO and VRBPAC recommended that the
strains selected for the previous year be used again: A/New
Caledonian/20/99, B/Hong Kong/330/01-like, and A/Moscow/10/199
(H3N2)-like.

As the season started in Northern Hemisphere and a new variant H3N2
began to predominate, however, reports of associated morbidity
significantly increased demand. Effectiveness of the vaccine to provide
protection against A/Fujian-like H3N2 became an important issue.

Dr. Weir then discussed what they are looking at for the 2004--2005
season. Global surveillance remains ongoing, and the spread of Avian
H5/N1 is being watched carefully. WHO recommendations for strain
selection will be made on February 11 to 13, and the VRBPAC
recommendations will be made at their meeting the following week on
February 18 to 19. VRBPAC recommendations will depend on the current
surveillance, and their meeting will also include discussions of
effectiveness studies and strategies for use of non-egg virus isolates
as reference strains for manufacturing. In summary, Dr. Weir explained
that changes in vaccines generally occur yearly to remain current with
circulating viruses. Though the timelines are somewhat inflexible, they
have already been streamlined as much as possible to accommodate
surveillance, timing of influenza appearance, and manufacturing.

**Public Perception of Influenza/Influenza Vaccine - Dr. Glen Nowak**

Dr. Nowak provided findings from studies on public perception and
influenza. He discussed several influenza vaccination communication
studies. The studies were the HealthStyles panel survey, the
RoperASW/NFID telephone survey, the HealthStyles Recontact Panel survey,
the Associated Pres-Ipsos Poll, the Harvard telephone surveys, and the
Harris Interactive/Wall Street Journal online surveys. Most of the
studies were conducted in December (AP poll, Harvard telephone surveys,
Harris interactive studies) as the season was unfolding and, with the
exception of the second Harris study, before there were reports about
the actual efficacy of the vaccine.

Findings from these studies are counter to expectations that experts
have assumed about the public and influenza. These assumptions have
typically been: most people over 65 are not well informed; most
Americans are not aware that flu can be prevented with vaccination; most
Americans do not believe that flu can be a very serious illness; most
Americans think that the vaccine protects against a wide variety of
illnesses and germs; and it is relatively easy to persuade more
Americans to get vaccinated by using the word "influenza" instead of
"flu" by telling them that it is a serious disease, or by getting
celebrities to tell people to get vaccinated. Data from the influenza
studies challenge many of these assumptions.

Key findings of the RoperASW study showed that 84% of respondents said
they were aware that the flu could be prevented by vaccination and 82%
of those over 65 get the vaccination. The studies also showed that
respondents were generally well-informed about influenza: 94% were aware
that flu can lead to hospitalization and possibly death; 77% of people
are aware that healthy people should get vaccinated; 75% were aware that
December was not too late to get a flu shot; and only 1% said that SARS
is a reason to get the flu vaccination. The findings also showed that
42% believed that someone in their home would catch the flu, so people
were aware that this could be a real threat to their health or their
family's health. People, however, did generally underestimate the number
who would suffer serious complications from influenza---they estimated
that about 5,000 people per year die versus the actual 36,000. About 90%
of people said they wash their hands, dress warmly, ate healthy, and
took vitamins to help prevent the flu.

Dr. Nowak then discussed the HealthStyles Fall Survey done in October.
Key findings showed that overall, 48% indicated that they had already
received a flu vaccination or planned to get one. Most respondents said
they were "well-informed" about who should receive an annual flu
vaccination and about the vaccine's benefits and risks. About two-thirds
(63%) said they had recently read or heard something about flu shots or
vaccine in the media. The study also showed that about 47% were
vaccinated at a doctor's office or HMO, which is consistent with other
studies.

People who did not receive the flu shot were asked the primary reasons
why they did not get one, and most people gave more than one reason.
These reasons were that 26% said they did not need it; 24% cited
allergic or other reactions; 23% said that no health professional had
recommended one; 22% did not believe they were likely to get the flu;
18% did not think the illness caused by the flu was serious enough to
get vaccinated; 15% did not believe the flu vaccine was effective; and,
9% were not sure if they needed it.

Dr. Nowak then discussed the first of the two Harvard studies. Again,
results show that a large percentage of people aged 65 years and older
(71%) indicated that they received a flu shot this season. However, 47%
of people with chronic illnesses said they did not get a flu
vaccination. The study also looked at people who chose not to get the
flu shot (about 50% of respondents). Although many had more than one
reason for not getting vaccinated, there were three primary reasons: 54%
did not believe they were at risk of getting a serious case of the flu;
45% did not believe the vaccine was effective in preventing them from
getting the flu; and, 42% were concerned about the side effects or
reactions to the flu shot.

Dr. Nowak noted that there is evidence from the studies that the
collective efforts of CDC, healthcare professionals, and other partners,
through education and outreach, appear to have made a significant
impact. For example, a large majority of the public is well informed
about influenza vaccination and has a relatively accurate understanding
of influenza illness, especially people aged 65 years and older, and
many can recall the key messages. Furthermore, more people appear to
have received or sought a flu vaccination this year than in previous
years, up to a 10% increase.

The studies also suggest, along with the experience in the last couple
of months, that realities and perceptions regarding disease/virus
prevalence and severity do matter and that they quickly and strongly
affect interest, motivation, and behavior regarding to vaccination. For
people who choose not to be vaccinated, the perception that they will
not experience severe complications from the flu is strong, and for the
most part, this is in line with experienced and statistical realities.
For the vast majority, influenza is not life threatening. Furthermore,
people know from experience and experts that some seasons/strains of
influenza are more virulent and harmful than others, and interest and
demand will vary annually based on how severe the season appears to be.
The variance could be significant even as we try to convince more people
to get an annual vaccination.

In conclusion, Dr. Nowak noted that generating additional significant
increases in consumer demand for the influenza vaccine will be
challenging. Barriers, such as doubts about the efficacy or value of the
vaccine, will need to be addressed. Furthermore, it will require
persuading and motivating people other than those aged 65 years and
older, particularly parents, people aged 50 to 64 years, and people with
chronic illnesses that place them at risk of serious complications.

**Perspectives of Influenza Vaccine Manufacturer, Aventis Pasteur - Ms.
Christine Grant**

Ms. Grant thanked Dr. Gellin, Dr. Beato, and Dr. Peter for inviting the
manufacturers to the meeting, which she believes is a best practice. She
explained that she would discuss lessons learned about vaccine supply
and demand, the experience in this past season, and some
recommendations. Ms. Grant emphasized that from a manufacturer's
perspective with 30 years of experience, demand has driven the doubling
of supply and will continue to drive increases in the future.

Aventis Pasteur accounts for 50% of the world's influenza vaccine
supply. Their plant in Swiftwater, PA produces 50% of influenza vaccines
sold in the U.S. The company has plans for additional manufacturing and
is well on its way on increasing its filling and packaging capacity. She
announced a new partnership with the Crucell Organization after
extensive research on an optimal cell culture/cell line approach. They
looked at characteristics such as potential yield and the fact that cell
line can be grown in suspension. She cautioned that Aventis Pasteur
believes that while they are hopeful for innovative technology, it will
be a multi-year project before a product that meets everyone's
expectations, including licensing requirements, can be brought into the
U.S. and commercialized in Europe.

In the 2003--2004 season, Aventis Pasteur shipped approximately 43
million doses of influenza vaccine in the U.S.

Ms. Grant discussed the three phases of the influenza season. They work
very interactively, pre-season and throughout the season, with FDA and
CDC as the vaccine goes through the manufacturing process. Beginning
with the January to May phase, she explained that it is not unusual for
manufacturers to go at risk before the new year starts and the final
strain has been approved. They make a best judgment in consultation with
others (though it is ultimately the manufacturer's choice) to start with
one strain to further compress the timeline, wherever possible. The
first step is seed preparation. The virus is then grown in millions of
fertilized eggs, which are required for the activation process. The next
phase is June to August, when the strains go through a company and FDA
testing process. Each lot is released---based sequentially on good
tests. The vaccine starts to flow into the market in the August to
December timeframe. This year, distribution was completed by November 1.

Ms. Grant presented another perspective on the manufacturing timeline
since people always ask where the timeline can be compressed and what
can be done differently. This perspective shows a 10-week process,
beginning after spring decisions are made and starting with the
preparation of the monovalent concentrate. CBER is periodically involved
and provides a quick turnaround in the review. Aventis Pasteur believes
they manage the process well on their end, considering that the
variables every year depend on yield. The quality assurance process
cannot be compressed since it is a human vaccine.

She then discussed the projected supply to the U.S. market. The industry
estimated capacity for the upcoming year is 83 to 100 million doses of
trivalent vaccine. Since they do not share information with competitors,
they rely heavily on the government projections. The goal is to
distribute vaccine by the first week of November, but this depends on
public announcement, final decisions about the strain, and strain yield.
The vaccine supply in the U.S. has more than doubled in the last 10
years to meet or exceed the market demand. Supply has, over the past 10
years, tended to increase demand---"demand" being the actual vaccine
produced and sold. She noted that the vaccine return policies have
changed over the past years, and it was not unusual for unused vaccines
to be returned. Capacity could expand further, but demand drives the
supply.

Another way to increase supply is to work together to extend the
immunization system, and manufacturers can, in turn, discuss increasing
production.

Ms. Grant moved on to discuss recent trends in the supply/demand
environment. In 2002, 12 million doses intended for the U.S. market were
discarded due to insufficient demand. This is likely an underestimate
since reportedly several million doses of unsold vaccines were not
returned. In 2003, the vaccine orders were down significantly,
indicating that demand would be less than in the prior season. The
company has 30 years of experience with people in the production,
scientific, regulatory, and commercial operations areas. They look at
pre-ordering, which started on December 1 for the upcoming season. They
routinely factor in a cushion in case demand is underestimated, though
they are also concerned with the inefficiencies and costs associated
with wasted vaccines. She noted that in the past year, the boost in
demand occurred after their production had ended. With the influenza
outbreak occurring earlier than usual this year, there was an
end-of-the-season unanticipated demand after production was completed.
In the third quarter, it appeared that there would again be several
millions of doses of unused vaccines. However, they began receiving
several calls from private sector clients who were seeing a surge in
demand based on media reports of outbreaks and pediatric deaths. Aventis
Pasteur proactively notified CDC of the late surge and worked with them
to reserve and allocate any small amounts of unused vaccines for use by
the states (100,000 additional doses of Fluzone and 150,000 doses of
pediatric P-Free influenza vaccine).

Ms. Grant then discussed preparation for the 2004--2005 influenza
season. Pre-orders drive vaccine production, considering that demand
drives supply over time and that this will be the first season
experiencing pediatric recommendations. The pre-order process began on
December 1, 2003, and in general, does not appear overwhelming. Since
they do not see anything unusual, everyone will have to work together to
plan. They are giving a targeted notice to those who plan on ordering
the vaccine (both public and private) to remind them that this
pre-ordering period is the time to think about plans for September and
October, despite the fact that they educate the public in the fall.

Aventis Pasteur has developed an equitable allocation and distribution
policy in coordination with public health and medical authorities in
discussions of the Flu Summit Group. They make every effort and have
been successful in ensuring that everyone affected (e.g. state, county,
public health clinics, private sector, larger organizations) gets a
share of their orders as the vaccines are distributed, the season
progresses, and until all orders are filled. Most people do not realize
that 85% of influenza vaccine doses sold in the U.S. are actually
distributed and administered in the private sector. Aventis Pasteur
provides about 70% of the remaining 15% of doses that are purchased by
the public sector.

Ms. Grant discussed the influenza vaccine market, which is increasingly
a private purchase system. Private sector demand has double since 1991
but has plateaued over the past few years. She noted that the adult
vaccine system, unlike the children's vaccine system, is very heavily
dependent on the private sector for delivery and administration. Aventis
reinforced the need to promote provider and consumer education on
influenza immunization recommendations and to encourage healthcare
providers to order the vaccine early. Innovative and sustainable
initiatives would help drive demand. Lastly, the medical community needs
to set an example by urging healthcare workers to routinely get
immunized.

She acknowledged the synergy of DHHS agencies and a great opportunity to
forge partnerships among private sector stakeholders and public
agencies. She suggested that CDC gather and publish annual influenza
rates by risk group, since people tend to look at this information state
by state, and noted the importance of CDC's continued work to increase
public confidence. CMS has also worked hard in the last couple of years
to see that reimbursement for physician administration did not decline.
They are sitting on a wealth of access to information for Medicare and
Medicaid providers and have a routine way of communicating with them.
This is an opportunity to remind them that at the front end of the
season is the time to start thinking about their immunization program.
Similarly, CMS has access to information by zip code on who is and is
not being immunized. Aventis Pasteur is confident that CMS will publish
timely reimbursement notices regarding fees since clinicians are clearly
concerned about this. Finally, FDA should continue working to ensure
public confidence on safety and efficacy.

Ms. Grant referred back to her discussion of extending the immunization
season and increasing immunization rates among healthcare professionals.
She suggested that there are also ways that the insurers and managed
caregivers can work on an immunization campaign to cover tens of
millions of Americans.

Ms. Grant discussed what Dr. Beato called "stockpiles," which Aventis
Pasteur refers to as "strategic reserves." Manufacturers understands
that there may be a need for the government, at the front end of season,
to negotiate with manufacturers to ensure that vaccines are available in
the event of unanticipated demand or outbreaks. Aventis Pasteur looks
forward to working with CDC and DHHS on this issue. This does not,
however, substitute for the difficult job of seeing that demand is
increased over time.

In conclusion, the optimal solution to achieve the *Healthy People 2010*
goal and pandemic preparedness is to increase annual immunization rates.
Increased demand will, in turn, increase supply and capacity in a market
that is becoming exciting and competitive. Aventis Pasteur plans to
expand egg-based capacity and is working on innovative cell culture
approaches. They encourage immediate attention to "strategic reserves."
They need to immediately begin planning for shared-risk reserves for
surges to ensure availability for the 2004--2005 season.

**Chiron Vaccines - Dr. Clem Lewin**

Dr. Lewin noted that Chiron is a part of Chiron Corporation, a
biotechnology company located in Emeryville, California. He thanked Dr.
Peter and Dr. Gellin for the opportunity to present to NVAC. He welcomed
this and continued opportunities for dialogue and feedback.

Dr. Lewin explained that his presentation would provide an overview of
Chiron, their 2003 production, a view of the future, lessons learned in
2003, and preliminary recommendations on how the supply shortage can be
addressed in the future.

Chiron Vaccines is the fifth largest vaccine producer in world,
producing both pediatric and adult vaccines. They are one of the leading
producers of the oral polio vaccine and distribute more than 8 million
doses annually. Despite only being 25 years old, Chiron Vaccines has a
rich heritage based on the companies they have acquired, mainly European
vaccine companies that have up to a 100-year history. In July, they
purchased PowderJect, which produces Fluvirin, and are now the second
largest flu vaccine producer with a global presence. They have
manufacturing facilities in Liverpool, United Kingdom; Marburg, Germany;
and Siena, Italy. They provide Fluvirin, RabAvert, and tetanus and
diphtheria bulks in the U.S. and have a vaccine for meningitis C
currently in Phase III trials in the U.S.

In 2003, Chiron supplied approximately 38 million doses of Fluvirin, a
50% increase from 2002, and made them available to distributors from
August to early November. The supply of Fluvirin to the U.S. more than
tripled from 2000 (12 million doses) to 2003. At CDC's request for
additional influenza vaccines, Chiron estimated that they had 360,000
vaccines in bulk to provide, which were FDA-licensed and delivered in
early January.

In 2004, Chiron plans to produce approximately 50 million doses. The
exact volume of the doses depends each year on factors such as yield and
assumes that all plans go as anticipated. They plan to deliver the
vaccines in the same time frame as 2003. Plans are in place to expand
production further if demand for vaccine exists, since supply tends to
follow demand. Finally, Chiron is currently in discussions with FDA
about a cell culture vaccine using an MDCK cell mine. The product has
completed Phase II for European approval, and a scaled up production
process is available. However, Dr. Lewin provided the same caution as
other speakers regarding the longer timeframe required to obtain FDA
approval and license for new products.

Dr. Lewin shared Chiron's lessons learned in 2003. He explained that the
only thing that is predictable about influenza season is that it is
completely unpredictable. A severe epidemic can cause surge in demand,
as can media attention. However, it is difficult, if not impossible, to
adjust the supply. By the time the severity of the epidemic is known, it
is too late to increase production. They also learned the importance of
open channels of communication between the manufacturers, CDC, and DHHS
about the ability to respond with additional doses and to coordinate
activities. He noted Dr. Nowak's point that they achieved the highest
immunization rates for influenza, so this season was both a challenge
and an accomplishment from a public health perspective.

There have been many discussions by Congress and others about a
guaranteed purchase program for the influenza vaccine in the U.S. Chiron
is prepared to extend the production season to deliver additional doses
in late November and December. They do not currently do this since the
demand for influenza vaccine tends to drop after Thanksgiving, and they
do not know if there is going to be increased demand unless there is
severe disease. The result could mean unused vaccines that would have to
be destroyed. A decision to increase the supply must be made by January
to ensure an adequate supply of eggs to produce the vaccine, and the
vaccine purchases must be placed prior to this decision with no
knowledge of the severity of the season. To maximize the benefits of the
program, Chiron believes that any purchase program should be distributed
among all vaccine manufacturers rather than having a "winner takes all"
situation.

Dr. Lewin added that Chiron has concerns about the long-term viability
of a purchase program where vaccines are destroyed. While a purchase
program may meet short-term goals, the demand for the vaccine must
increase in the long-term. While government involvement may be
appropriate and necessary, there could be unintended consequences that
they must be cognizant of and manage properly. A lot of the
manufacturing is in the private sector, and therefore, large-scale
government purchases have the potential of destroying the current
private sector distribution system for influenza vaccines. Chiron does
believe that it is possible to create and manage a program that has no
negative consequences and does not destroy the current system.

Chiron believes that increasing influenza vaccine demand under routine
circumstance is the best market efficiency solution for the episodic
surges in demand since it can balance client demand in a severe upswing.
He noted that previous presentations showed that outreach has increased
immunization coverage in the age group over 65 years old. Chiron
believes that the same efforts must be made for other recommended groups
to raise demand. There is a need to raise awareness of influenza
immunization recommendations, develop innovative programs to highlight
the benefit of the vaccine and to facilitate access, and extend the
immunization season into December.

Dr. Lewin noted that the findings on attitudes towards immunization are
encouraging. People are aware of vaccines and other issues, so the best
way to build on the lessons learned must be determined for both elderly
and pediatric populations to increase the coverage rates. Again, he
noted that the best way to increase supply is to increase demand under
routine circumstance and referred to an editorial in the recent January
15 issue the *New England Journal of Medicine* that makes the same
recommendation.

**MedImmune/Wyeth -Dr. Peter Paradiso**

Dr. Paradiso noted that he is representing MedImmune and Wyeth, though
he works for Wyeth.

Dr. Paradiso began by explaining that they introduced a new vaccine in
the U.S. this year. They learned a lot about launching a new product in
an environment where there is already a known product on the market and
wanted to share on their experience with FluMist. Buyers are not quick
to move to new things and innovations. They did a significant media
blitz and believe it contributed to the increased awareness about
influenza vaccination. The message needs, however, to be repeated.

Dr. Paradiso stated that it is obvious that we are driving demand up for
a number of reasons and in a number of ways. The CDC net *Healthy People
2010* goals have been suggested. In order to be prepared for a pandemic,
annual vaccine use is critical. Forecasting demand is also critical.
There are risks involved in trying to forecast demand and matching
supply to goals. In, 2002, over 90 million doses were produced and over
20% were discarded, while fewer than 90 million doses were produced in
2003 and there was a vaccine shortage. Dr. Paradiso noted that this was
the first year with a shortage. In the previous few years, there was a
vaccine shortage in October and November, but vaccines were being thrown
away in December. There are lessons to be learned from this year and how
demand is driven.

In general, vaccination campaigns begin in October and end in November,
regardless of the timing of the supply, and the month of peak influenza
activity varies from year to year. Ordinarily, flu activity begins and
vaccination stops, so the concept of vaccinating into the influenza
season does not seem to catch on. In 2002, the vaccine has been late
arriving, and although the epidemic did not occur until January and
February, there was essentially no vaccination occurring in February. In
2004, influenza activity began while vaccination was still occurring, so
the connection between the influenza activity and the availability of
the vaccine came at the same time. As a result, demand for the vaccine
went beyond November into December. To his knowledge, this is the first
real vaccine shortage because we vaccinated into the epidemic, and in
his opinion, they should vaccinate into the epidemic, every year
regardless of when the epidemic occurs.

In early December, there was an announcement about the widespread
disease especially among children and the limited vaccine supply. Wyeth,
in an attempt to make it easier to supply the vaccine, decreased the
cost of FluMist to \$20 per dose. The result, however, was disappointing
with only about 75,000 doses of FluMist distributed and millions of
doses remaining unused. While the aging patients and the population for
which the vaccine is indicated are limited, most of the illnesses and
deaths occurred in populations that could have been vaccinated.

Dr. Paradiso presented data on influenza-associated deaths in children
less than 18 years of age for the 2003--2004 influenza season. FluMist
is recommended for children between the ages of 5 and 18 years, and the
data show that about 40% of deaths occurred among children in this age
group. In terms of FluMist eligibility, there is a fair percent of the
population who was not part of the recommended population and a high
percentage of these people get and spread influenza.

In looking back at the track record for influenza vaccination, Dr.
Paradiso referred to Dr. Beato's remarks and questioned if we have the
correct paradigm for influenza vaccination. We have heard that 60% to
70% of the elderly (over 65 years of age) are vaccinated annually.
Although this is a good rate, it may be possible to raise this by 10% to
meet the *Health People 2010* goals of 90%. Many patients value the
vaccination because of its efficacy, and all major high-risk groups are
targeted. Significant epidemics still occur annually even though 80
million doses are distributed each year. A new way of managing influenza
is needed.

Dr. Paradiso commented that the broad population should be vaccinated,
especially children. Protecting the elderly requires protecting the
infectors. He used the strep pneumococcal vaccine as an example. If we
broadly vaccinate children against infectious agents such as
pneumococcus, for example, many populations outside of those vaccinated
will be protected because children are infectors. A similar effect would
occur with broad vaccination of children, especially school age
children, against influenza.

Vaccination campaigns need to begin as soon as the vaccine is available
and continue until the epidemic is over. Because the literature state
that October and November are the best months. The message needs to be
changed to let people know that while there are good months to be
vaccinated, people can be vaccinated at other times as well. New and
improved vaccines need to be introduced, if and when possible, and
vaccinations should be stockpiled to meet goals. Dr. Paradiso expressed
some doubt with regard to increasing the number of vaccine suppliers as
a solution. The trend in demand may be more useful in alleviating the
problem.

He noted that the current regulatory environment has made it difficult
to introduce innovative, new vaccines. New vaccines are very expensive
and regulatory hurdles are very high. The FluMist investment has been
very substantial \$1 billion over a large number of years. The companies
had to introduce the vaccine with a very conservative label that
indicates use in healthy children aged 5 to 17 years of age and healthy
adults 18-49 years of age as a first step. This is expected to broaden
over the coming years, but it is very difficult to sustain a business
while doing this.

The reticence on the part of physicians, the public health community and
the government to promote the use of new products and distinguish
between old and new products has also made it difficult to introduce new
products. There were many barriers in health clinics, and
misinterpretations of some of the precautions to the vaccine hurt its
use.

Dr. Paradiso concluded by emphasizing the need for a new paradigm to
control influenza disease. Innovation must be encouraged and rewarded
whether it be cell culture, other vaccines, or another technology. Risk,
especially of producing supply, must be shared.

**Baxter - Dr. Joan Fusco**

Dr. Fusco thanked NVAC for the invitation to present and explained that
she would be providing a glimpse into what Baxter Vaccines hopes is in
the not-too-distant future. She noted that they were the only
non-U.S.-licensed vaccine manufacturer represented at the meeting. Her
presentation focused on an overview of Baxter Vaccines and Vero cell
culture platform technology, its application to influenza, how it can be
complementary to existing egg-based vaccines, and some of the benefits
and problems with cell-based vaccines.

Baxter Vaccines is a part of the bioscience division of Baxter
International, global healthcare company. Their vision is to be leader
in infectious disease vaccines and to focus on next generation products
and technology for influenza, bio-defense, meningococcal disease, and
insect-born diseases. Baxter currently has two licensed products: an
encephalitis vaccine licensed in Europe and a meningococcal C vaccine
licensed in 35 countries around the world.

Dr. Fusco explained that Baxter Vaccines has partnerships with
companies, such as Acambis, to produce small pox and other vaccines. It
is also working with the U.S. government to develop a SARS vaccine.

Dr. Fusco provided background on Vero cell technology. Baxter can create
master cell banks and working cell banks, and these banks have been
tested for absence of tumorigenicity, absence of adventitious agents,
and identity/genetic stability. They grow cells in microcarriers in
fermenters and have expanded their capacity over the last few years. She
noted it is a fairly permissive system for multiple viruses. Some of the
benefits of using this microcarrier Vero technology include a continuous
cell line, acceptance for production of licensed vaccines, a serum
protein free medium, high yield of virus antigens, high purity of virus
vaccine preparations, and high safety of virus vaccines. It is also
permissive for a multitude of viruses and wild-type viruses.Dr. Fusco
then described the Vero cell-derived pandemic influenza vaccine
formulation, which they have completed and tested in Europe. They grow
the virus on a qualified continuous cell line and use an egg-derived
wild-type seed virus provided by WHO. There is no requirement for high
growth reassortants; they naturally get the virus to grow in a
reproducible way in the cell culture. This whole virus inactivated
vaccine is free of preservatives, antibiotics, and egg protein.

She noted that some clinical data are available. These data show that
the majority of local reactions observed, in seven studies with nine
different vaccine lots, over four influenza seasons in Europe were mild,
very few moderate, and none severe. Systemic adverse events were
minimal. The frequency and severity of the local systemic reactions to
the Vero derived whole virus influenza vaccine are comparable with
licensed egg derived split influenza vaccines. Baxter has applied for a
product license for European Community-wide registration in a Mutual
Recognition Procedure (MRP) this year and received First National
Licensure in the Reference Member State (RMS) in February 2002. They are
also working with the FDA to begin U.S.-phase clinical trials this year.

Dr. Fusco then shared Baxter's view on how cell culture influenza
vaccine complements current efforts. With wild-type viruses, they do not
have to wait for reassortants. Hypothetically, they could provide a
vaccine earlier in the season and could continue to supply vaccine by
turning to their on-demand subsidiary. Depending on what is reported,
they could also make course direction changes, if necessary. She noted
that for a pandemic, they have the flexibility to grow wild-type
viruses. Again, there is no need for attenuated reassortant that
requires time to generate and may be unstable. They could begin delivery
within 7 weeks of identifying the virus. Dr. Fusco explained that they
are in the process of bringing Vero cell influenza vaccine into the U.S.
from Europe. A Vero cell influenza vaccine is an alternative in the
not-too-distant future and provides flexibility during both the season
and a pandemic.

**Public Sector Roles in Adult and Childhood Influenza Vaccination - Dr.
Lance E. Rodewald**

Dr. Rodewald provided an overview of the public sector role in influenza
vaccination. He began by explaining that the differences between public
sector roles for childhood and adult are not upstream. He noted that for
childhood public purchases, the CDC uses a vaccine replacement model.
The VFC program allows vaccine purchases using federal and state funds
and is used to provide government-purchased vaccines to providers for
administration to patients. Unlike the adult program, this program has
stockpile authority and funding, which is a major asset.

For adult vaccine public purchase, a vaccine reimbursement model is
used. This fee-for-service model reimburses the provider after the
vaccine is administered and is primarily administered through Medicare
and Medicaid. The differences between the programs for providers are the
up-front purchase costs and the financial risk. He noted that
manufacturers do not offer vaccine return policies.

Dr. Rodewald explained that the childhood public delivery system has
approximately 100,000 public health providers operating at 45,000
vaccination sites. The latest data from the 2002 immunization survey
show that the VFC program reaches more than 90% of preschool children.
He added that children's immunization is integrated into primary care,
which is a very important concept because immunization is one of many
services that need to be delivered. VFC promoted the program heavily.

The adult public delivery system has approximately 3,000 vaccination
sites, which are primarily the local health department clinics. He noted
that these are the public sector sites and do not include all of the
public-purchased vaccines.

There are several evidence-based childhood public interventions to
sustain and improve coverage rates. The first intervention is to
minimize the cost barrier. The Section 317 discretionary program and
state purchase help minimize costs for both parents and providers who
purchase the vaccine. VFC has a provider quality improvement aspect to
the program that allows states to work with VFC-involved private sector
immunization providers to improve their immunization coverage practices
according to NVAC standards published last fall. In addition, school and
day care laws are a potential intervention for influenza, depending on
how the vaccination paradigm shifts. He noted that surveillance for
coverage and safety is very similar for children and adults.

Dr. Rodewald then discussed immunization policies and finances. For
childhood vaccines, ACIP is a powerful organization that recommends the
schedule and target population for influenza vaccination. It also has
the authority to raise the funds for VFC-eligible children, which is
very unusual for an advisory committee. For adults, ACIP recommends the
schedule and target populations, but has no real authority to finance
vaccines. Since the intent of discretionary 317 funds is to immunize
children, only an estimated 5% of are used for adults. States also raise
funds for adult immunization.

He also noted that the CDC and states control the vaccine for routine
childhood, but there is very little public sector control for routine
adult and minimal control for targeted, high-risk adults. In addition,
the burden of vaccination assurance lies with CDC and states for routine
childhood but that there is no clear public sector lead for assuring
vaccination for high-risk adults.

Dr. Rodewald noted that the childhood program is very effective and
explained that there has been a rapid increase in coverage with new
vaccines. Among adults, influenza vaccination coverage rates have
experienced a plateau. There is, however, a disturbing discrepancy among
racial/ethnic adults.

In conclusion, Dr. Rodewald explained that the public sector routine
childhood program is almost fully funded, delivers more than 50% of
childhood vaccines, and is highly effective with new vaccines. The
public sector adult program administers about 6% of influenza vaccine
through local health department clinics and has a relatively small
public health infrastructure.

**CMS: Financing and Quality Improvement Organizations Efforts - Dr.
James Randolph Farris**

Dr. Farris discussed recent efforts by CMS to increase immunization
rates among Medicare beneficiaries. He learned a lot today and heard
many comments that he would not have heard a couple of years ago at a
meeting like this. There is recognition of the efforts that CMS has made
to improve immunization rates and to work with groups such as NVAC to
come up with a viable solution to the problems.

About 39 years ago, the Medicare program had no preventive services. In
1981, they began coverage of pneumococcal immunizations and in 1993
added coverage of influenza immunizations. Those familiar with the
Medicare Modernization Act (MMA) and its phases are aware of the fact
that there will be opportunities to increase preventive services. Under
MMA, Medicare will begin covering physical exams, and this will provide
an opportune setting to talk to Medicare patients about the need for
preventive services including, as specifically mentioned in the bill,
influenza. This will in turn be an opportunity to increase the level of
influenza immunization coverage, as well as pneumococcal immunizations,
among Medicare recipients.

CMS is committed to the goal of increasing coverage of Medicare
beneficiaries for influenza and pneumococcal vaccines, and has included
it as one its GPRA goals. Dr. Farris discussed working with Quality
Insurance Organizations (QIOs), once called peer review organizations.
QIOs make certain that CMS provides good, reasonable services to
Medicare beneficiaries. They see to it that services are provided in a
timely manner, are given in appropriate setting, meet medical necessity,
and meet quality standards. A QIO exists in each state and part of their
charge is to reduce mortality due to pneumonia. They are charged with a
task of increasing influenza and pneumococcal immunizations in each
state. They are also required to screen patients in hospitals to see
that those patients have been offered or have received influenza and
pneumococcal vaccines. This gives them the opportunity to work with
physicians. Part of QIO duties is to work with physicians in office and
hospital settings to talk about current trends and methods to make
certain that physicians know what is appropriate in terms of provision
of quality services.

He noted some CMS special project, though not specifically for
influenza, that involve working to increase pneumococcal immunizations
through faith-based organizations, schools, and pharmacies.

Dr. Farris noted that immunization in institutional settings offers a
unique opportunity to improve immunization rates. Many Medicare
beneficiaries spend time in hospitals and nursing homes and many receive
home healthcare services. Since healthcare needs are greater for these
individuals, standing order programs for vaccine administration went
into effect in October 2002.

Finally, he noted that there has been an increase in the administration
fee for influenza and pneumococcal vaccinations that increased an
average of 94% (related to physician fee schedule). Dr. Farris reassured
the committee that CMS will work with QIO and regional office
coordinators to make sure that the exact price Medicare will pay for
influenza and pneumococcal immunizations and physician fees are on their
websites. This will solve a number of problems.

**Perspective of Health Plans and Insurers - Mr. Bob Rehm**

Mr. Rehm began his presentation by thanking Dr. Peter, Dr. Gellin, and
Dr. Black. He explained that AAHP-HIAA is the national trade association
representing the private sector in healthcare. It has nearly 1,300
member companies that provide health, long-term care, dental,
disability, and supplemental coverage to more than 200 million
Americans.

Dr. Rehm focused his presentation on coverage policies, public reporting
on performance, targeted organizational initiatives, community outreach
efforts by both AAHP-HIAA and health plan members, and challenges and
opportunities.

AAHP-HIAA's latest data collection on coverage policies was done in
2001. The study was an exhaustive assessment where the primary
respondents were chief medical offices (CMOs). The survey was sent to
280 health plans, representing about 70% of the total health plan
membership. The results showed that health plans cover vaccines
recommended by ACIP. This year included other preventive services such
as breast cancer screenings and colorectal cancer screenings.

AAHP-HIAA is planning a vaccination and immunization survey for Q3 2004.
They will be looking at different types of health insurers and are
hoping to get both health plan and insurer perspectives on many of the
questions that have been raised. The questions expected to be seen will
be included, and Dr. Rehm said that anyone interested in adding
questions can contact him.

He reviewed data from AAHP-HIAA's 2001 annual industry survey in which
results showed that close to 95% of health plans cover pneumococcal and
influenza vaccines for people at high risk.

Dr. Rehm commented that immunization rates, at least among health plan
members, continue to improve. He presented data showing improvements
demonstrated by health plans in childhood immunization. The data show
that health plans are, over time, effective in reaching out to their
membership and that providers are committed to improving rates. The data
show the percent of health plan members receiving childhood immunization
services in 2000 through 2003. Chicken pox/varicella vaccine has the
lowest rates but the steepest slope. Many are performing in the 90^th^
percentile but some are performing at 25^th^ percentile.

Dr. Rehm discussed AAHP-HIAA immunization initiatives, which are guided
by their Immunization Task Force. The Task Force is comprised of 12 to
15 immunization experts within health plans. AAHP-HIAA shares
immunization updates regularly with its members and the public via the
*Immunization Newsletter*. They also have a monthly magazine that, last
year, featured three articles specifically addressing immunization
issues.

AAHP highlights and promotes health plans' models that work in the field
of immunization. Their Grant for Innovation in Immunization Practices
Program supports future programs to improve immunization rates. This is
the second year where grants were given to a particular health plan to
support its effort to improve immunization rates in terms of a
population or target vaccine.

Dr. Rehm discussed the AAHP-HIAA 10-year contract with CDC to manage the
Vaccine Safety Datalink (VSD) project and the Clinical Immunizations
Safety Assessment (CISA) project. VSD is a large database project that
looks at the adverse effects of vaccines, and CISA is a more
patient-centered clinical assessment of vaccines. Dr. Rehm noted
AAHP-HIAA representation on national committees. He mentioned Dr. Black
as the NVAC liaison and DR. Robert Scalettar Blue Cross/Blue Shield as
the ACIP liaison.

Dr. Rehm discussed a community outreach program on influenza
immunization called the PARTNERS Project. This is a unique partnership
with CDC that began in 2000 and ended in 2002. The partnership was
formed to promote evidence-based preventive health services to health
plan members, employees, and their dependents.

**Influenza Vaccine R&D - Dr. Cristina Cassetti**

Dr. Cassetti explained that NIAID supports a wide range of research
activities from basic research to the clinical evaluation of the
vaccines, therapies, and diagnostics. This research involves industry
and academia. She noted that over the years, NIAID has supported several
research programs for the development of improved influenza vaccines.
One of the major goals of these programs is to develop vaccines that
have enhanced immunogenicity or are broadly protective against widely
divergent virus strains. Ideally, the goal is to produce a vaccine that
does not need to be updated each year.

Many of the research programs aim to improve TIV with adjuvants, mucosal
delivery, or increased dose. To develop a vaccine that does not need to
be updated, there are also programs that are developing new vaccines
that target conserved proteins, such as NP and M2. Ongoing clinical
trials, such as Dr. Arvin's, are elucidating the immune responses to
LAIV compared to TIV and natural infections.

Dr. Yoshihiro Kawaoka at the University of Wisconsin at Madison
developed reversed genetics technology in 1999 with NIAID support. This
powerful technology allows an understanding of the virus from a research
standpoint, provides a potentially faster and easier method to generate
the vaccine reference strains, and eliminates the need for working
directly with the clinical isolate. It allows the engineering of the HA
of pandemic virus strains without the basic amino acids at the cleavage
site which are associated with high virulence.

NIAID is also supporting research on new technologies that could more
rapidly produce influenza vaccines. This research includes a tissue
culture-based system as an alternative to eggs, DNA-based vaccines, and
recombinant baculovirus-expressed protein vaccines. They are also
supporting projects exploring new methods for vaccine delivery, such as
a skin patch and a gene gun.

**Pandemic Influenza Preparedness - Dr. Ben Schwartz**

Dr Schwartz provided an overview of the draft National Influenza
Pandemic Plan. The goals of the pandemic influenza response are to
decrease the burden of the disease, minimize the social disruption, and
reduce economic impacts.

Dr. Schwartz presented recent developments that have affected the
planning process, which started over 10 years ago. These developments
include increased focus on influenza and other health threats, such as
the avian influenza outbreaks (1997, 1999, 2003, 2004) and the global
spread of SARS. There have also been improved infrastructures and
technologies, including improved vaccine development technologies, new
antiviral medications, and new communications systems. The 2003--2004
influenza season also provided lessons-learned in vaccine supply and
demand.

The plan is divided into several different components. The core plan
describes national coordination and decision-making, provides an
overview of key preparedness issues, and outlines response actions at
national, state, and local levels. In addition to the core plan, there
are two guide documents. One provides guidance for state and local
health departments' planning process; the other provides guidance for
the healthcare system's planning process. There are also ten annexes
that will provide more detailed and technical information on key
preparedness and response issues.

The key intervention in a pandemic is vaccination. The vaccine and
vaccination preparedness goals are to assure surge production capacity,
shorten timelines to availability, and ensure effective distribution and
administration to achieve pandemic response goals. To approach these
goals, the first step is to assure year-round egg supply. Additionally,
U.S. manufacturing capacity must be increased, vaccine pilot lots for
strains with pandemic potential must be developed and tested, and
research to improve the ability to rapidly develop reference strains
that grow well in production systems must be conducted. A lot of
thinking is ongoing about the best way to deliver vaccine, especially to
traditionally underserved racial and ethnic communities.

Before vaccines will become available during a pandemic, antiviral drugs
are likely to be the most important intervention.

He noted that state and local preparedness is key because these are the
levels in which interventions are implemented. State and local health
departments are being supported with pandemic, bio-terrorism, other
preparedness planning. HRSA is providing grants to coordinate medical
care and enhance capacity in local communities, and CDC is providing
support for surveillance and public health laboratories. Another
activity involves developing tabletop and field exercises so that states
can look at the effectiveness of their plans. In the healthcare system,
there is also a need for planning and education, especially for
interventions that may be implemented at that level, such as triage and
infection control. HIPAC has recently revised the infection control
guidelines for influenza.

Dr. Schwartz presented the next steps in influenza pandemic
preparedness. The first step is to finalize the national plan. The
second step is to promote and support planning at state and local
levels, with testing of plans in tabletop and field exercises. The third
step is to address key issues to enhance preparedness improving response
capacity. The last step is to monitor the progress of the plan and
revise it accordingly.

**New Business Discussion**

Dr. Hinman made a motion to adopt a resolution that recognizes the
contributions of Dr. Orenstein. Dr. Hinman read the resolution, which
was passed out to the committee. The motion was seconded by Dr. Fast and
several others, and all voted in favor. Dr. Peter commented that NVAC
would not have been able to reach this point without Dr. Orenstein's
leadership. He thanked him on behalf of NVAC. -- ACTION -- NVAC
RESOLUTION RECOGNIZING DR. WALT ORENSTEIN

**Working Group Updates and Reports**

**Laboratory Containment of Wild Poliovirus in the United States, Phase
I: National Survey and Inventory Final Report - Dr. Ann Margaret Arvin
and Dr. Walter R. Dowdle**

**Needs and Recommendations for the U.S. Polio Vaccine Stockpile**

**Dr. Charles M. Helms**

Dr. Helms explained that in 1999, the ACIP recommended that inactivated
poliovirus vaccine (IPV) be used for reaching the mitigation of the U.S.
population, while oral poliovirus vaccine (OPV) be reserved for "mass
vaccination campaigns to control outbreaks." The sole U.S. manufacturer
of OPV has withdrawn from the market, making it difficult to implement
ACIP's recommendation. In February 1993, the NVAC/ACIP joint work group
was charged with creating a report that looked at this problem.

ACTION - The NVAC committee members all voted in favor of approving the
report and submitting it to the ACIP.

**Public Health Options for Implementing Vaccine Recommendations: A
Framework for State Decision Making - Dr. Donald Williamson**

Dr. Williamson began by explaining the factors that the workgroup
discussed. There were growing numbers of recommendations from ACIP and
an increase in scope and complexity of the schedule. There is an
increase in cost, while resources remain fixed. There is a growing
public cynicism about immunization and immunization requirements.
Expectations about total disease elimination and protection is
increasing. There is an increased international commitment to interrupt
transmission and achieve eradication. The final factor was the use of
school immunization requirements as a strategy to control transmission
and increase immunization coverage.

The problem is that state officials are faced with increased challenges
as they implement newly recommended vaccines. The strategy of the
workgroup is to help state policy makers develop guidance around this
issue. The process involved literature reviews, regional stakeholder
meetings, and workgroup deliberations. The literature reviews included
surveys on how immunization policies are currently made.

Dr. Williamson presented the conclusions of the stakeholder meetings.
First, immunizations are a benefit, not only to the individual, but also
to society as a whole. Thus, immunization requirements for entry into
daycare, school, and colleges have been repeatedly affirmed by society
in general. Second and most important, the process for state
decision-making regarding implementation of vaccine recommendations has
been effective. Finally, immunization requirements that do not consider
financial constraints will not be optimally effective. These
requirements need to be prioritized and the economic barriers include
more than payment of vaccines.

Dr. Williamson provided four general areas of recommendations. These
include guidelines for states to address national immunization
recommendations, effective implementation of state immunization
recommendations and requirements, monitoring implementation of state
immunization requirements, and development of new knowledge. These
recommendations are intended to be broad in application, though the
language is specific to school systems.

**Public Participation in Vaccine Decision Making - Ms. Ruth Katz**

Ms. Katz noted that the purpose of the Wingspread Group was to explore
how the immunization community might enhance public engagement in
decision-making about vaccine policy. The group was made up of
representatives from health professional organizations, government
agencies, academia, industry, NGOs, and private consultants. The group
developed a proposal to the Vaccine Policy Analysis Collaborative
(VPACE) that explored actions to further engage the public in vaccine
policy. NVAC has been asked to review the proposal and to recommend
additional activities. An NVAC workgroup was formed to do the homework
behind this request and to make its recommendations to the whole
committee. The workgroup was formed over the last few months and
includes Ms. Koslap-Petraco, Dr. Kline, Dr. Schaffner. Both Dr. Gellin
and Dr. Peter have served in an ex officio capacity.

The workgroup is now in the process of identifying individuals and
organizations who have been directly involved in engaging the public in
policy-making activities. The plan is to bring them or representatives
from those organizations, along with the Wingspread Group, to meet with
the workgroup in Washington, DC over the next several months. The WB
will report back to the committee on these meetings. The purpose of
these activities is not an attempt to identify mechanisms for addressing
issues of conflict resolution. Rather, it is about identifying ways to
go beyond the traditional stakeholders and to find ways to engage them.
Towards that goal, the workgroup hopes to be as creative and thoughtful
as those who have developed the VPACE proposal.

**Vaccine Financing -Dr. Hinman**

Dr. Hinman explained that the charge of the workgroup was to recommend a
process for systematic evaluation of the Institute of Medicine (IOM)
report. The IOM report contained three recommendations. The first
recommendation was the implementation of a new insurance mandate
confined with the government subsidy and doctorate plan for vaccines
recommended by ACIP. The second recommendation was DHHS should propose
changes in the ACIP membership procedures so that its recommendations
can associate vaccine coverage decisions with social benefits and costs,
including consideration of the impact of the price of vaccines on
recommendations for its use. The third recommendation is NVOP should
convene a series of stakeholder deliberations on the administrative,
technical, and legislative issues associated with the shift from a
vaccine purchase to a vaccine mandate, subsidy, and voucher finance
strategy. The members of the workgroup are Dr. Hinman, Dr. Arvin, Dr.
Black, Dr. Williamson, Dr. Klein, and Dr. Whitley-Williams.

He noted that the workgroup is seeking industry perspective on the IOM
options. NVAC currently has no industry members and industry will be
heavily affected by the option that is ultimately chosen. Consequently,
the workgroup recommends the following steps. First, solicit
representation and participation to serve on the workgroup from major
manufacturers in the pharmaceuticals and biotech industries. Second,
convene a stakeholder meeting in Spring 2004 to discuss the IOM options
in detail. Third, using the results from that meeting, the summary of
the NPI forum, the workgroup's surveys, as well as ongoing discussions
and consultations, begin to draft the NVAC report and present an outline
of that report at the next meeting.

**Monitoring Anthrax Vaccine Adverse Events Defense Medical Surveillance
System -**

**Dr. Jeff Davis and Dr. Michael McNeil**

Dr. Davis noted that NVAC was asked for input on the process of using
the Defense Medical Surveillance System (DMSS), which is a composite of
several different databases, and to probe the potential of adverse
events occurring as a result of using anthrax vaccine. The workgroup met
to work out a mechanism to evaluate a variety of different proposals for
using DMSS. They undertook a rigorous process to understand the
protocol, weighing the proposals based on standard criteria, and
ultimately selecting several proposals for further investigation.

The proposed high-ranking topics for full protocols include arthritis,
erythema multiforme, optic neuritis, systemic lupus erythematosus, and
multiple immunizations. The workgroup is not sure of any particular
pathogenic mechanism for contributing to adverse events, but felt that
arthritis was a good topic. Erythema multiforme is a rare and severe
adverse event, and is also autoimmune-related. There is also strength in
the database, which would allow examination of optic neuritis in the Air
Force.

Dr. McNeil presented the timeline for the NVAC Vaccine Analytic Unit
Workgroup. The workgroup was formed in June 2003. They prioritized their
topics between July 2003 and February 2004, and will be launching a
protocol review by the June 2004 meeting. One of the next steps is to
continue DMSS data validation, which is a learning process that will
take a couple of months to finish. The second step is for CDC to award a
contract for chart abstraction. This is an important step for data
validation and specific protocols for particular adverse events. A third
step is to draft full protocols for selected topics for IRB approval.
The final next step is to continue the NVAC workgroup review.

Dr. Davis added that the workgroup did not formulate a formal
recommendation, but rather helped to evaluate the proposals. He also
noted that the potential for this database is extraordinary.

**Subcommittee Updates and Reports**

**Subcommittee on Immunization Coverage - Dr. Patricia N.
Whitley-Williams**

Dr. Whitley-Williams noted that the first topic discussed in the
subcommittee has been covered by the Polio Vaccine Stockpile
presentation. The second topic involves developing a white paper on
adult immunization, which has been discussed at a SC meeting prior to
the influenza season. As a result of their experience with influenza, a
proposal was made to have the white paper focus on influenza, as well as
barriers and strategies to improve adult immunization coverage. As a
rationale for this proposal, Dr. Whitley-Williams noted the 1991 NVAC
measles white paper, which put forth recommendations to overcome the
measles outbreak. However, there is only one recommendation that deals
specifically with measles. The other recommendations and strategies
actually look at the immunization delivery program and vaccine
development for the childhood immunization program. The subcommittee
hopes to mirror those efforts for the adult immunization program.

**Subcommittee on Future Vaccines - Dr. Patricia Fast**

Dr. Fast noted that the subcommittee reviewed the progress of three
different workshops in their report. The report on the CMV workshop has
been accepted by Clinical Infectious Disease and will be sent to Dr.
Beato for his final review. The pneumococcal vaccine workshop was called
September 2003. The workshop was to identify the extent of protection
against pneumococcal disease and to consider how existing and future
vaccines can be tested in clinical trials. The workshop was successful
in bringing together representatives from industry, government, and
academic research. Almost all of the presentations are available on the
NVPO website and a brief summary is being prepared for publication.

Dr. Fast highlighted the First International Neonatal Vaccination
Workshop (INVW), scheduled for March 2--4 in McLean, VA. The workshop is
coordinated by the National Vaccine Advisory Committee\'s Future
Vaccines Subcommittee, CDC, the U.S. Food and Drug Administration, the
National Institutes of Health, and the Task Force for Child Survival and
Development, and is supported by a grant from the DHHS National Vaccine
Program Office. A steering group led by Trudy Murphy, CDC, planned the
workshop, and Dr. Fast noted that Dr. Murphy did a stellar job planning
the workshop.

INVW will explore the feasibility and safety of strategies to expand
protection of young infants against vaccine-preventable diseases,
including a variety of viral agents, diphtheria/tetanus/pertussis,
*haemophilus influenzae* type b, and pneumococcus.

Presentations by national and international experts will focus on the
immune responses of the neonate to vaccine antigens, review clinical
experience, consider expanded use of vaccines in the neonate from
industry and regulatory perspectives, and explore other strategies to
protect neonates, such as maternal immunization. There will be a broad
spectrum of people coming, including the national scientific press,
public organizations, and a number of scientists.

Dr. Fast noted that another topic was how the SC could contribute to the
report Dr. Beato has requested. The SC supports this request and
volunteers have been identified to work on this report. They believe
research focusing on the goal of improving influenza vaccine needs to be
on the agenda. The research would identify the epidemiology, laboratory,
clinical, and operational research gaps. They also believe that some
consideration should be given to possible organizational, structural, or
policy impediments to this research.

**Subcommittee on Vaccine Safety and Communication -Dr. Jerome Klein and
Dr. Christine Casey**

Dr. Klein noted that they discussed three areas: an update on the CDC
Thimerosal studies, an update on the Clinical Immunization Safety
Assessment Network, and an update from the ACIP/AFEB Smallpox Vaccine
Safety workgroup. He first presented highlights of the smallpox
presentation. According to the BMG January 2004 report, 650,000 military
personnel were screened and 566,900 were vaccinated. Seventy-one percent
were primary and 88% were male.

Dr. Klein noted the screening technique must have been very successful
in the absence of eczema vaccinatum or progressive vaccinia. There were
zero cases in the military, which shows the success of the screening
program. For the DHHS Smallpox Vaccination Program, the number screened
is not available.

Dr. Casey presented an update on the Clinical Immunization Safety
Assessment (CISA) network. The CISA network is a vaccine safety
initiative under contract with CDC. There are seven centers and they aim
to clarify hypotheses of clinical syndromes following vaccination by
addressing some of the challenging clinical vaccine safety questions at
the individual patient level for all ages.

The main focus of the network is to provide real-time clinical
consultation for complex vaccine safety queries from the medical
community. The goal is to increase understanding of the underlying
pathophysiology of vaccine associated adverse events and identify
genetic or risk factors for predisposed groups. For example, ADEM (Acute
Disseminated Encephalomyelitis) has been known to occur after
vaccination. CISA was able to have their commissioned researchers from
the Boston Medical Center staff a case prospectively in one of the
states. They connected with the primary care provider and with the
patient to review clinical scenarios and make recommendations.

They are planning a gradual rollout of the program in Summer 2004, but
have some scientific and nonscientific barriers. Dr. Casey noted the
nonscientific barriers to the CISA project. There are inherent
challenges since this is an innovative and complex project. There are
medico-legal concerns, most notably liability on distant consultation.
Another concern is reimbursement variability. There are Data Privacy
308(d) and HIPAA requirements to protect the patients. They have to
build a functional informatics system. They have to effectively
communicate their goals to the public, providers, and partners. Finally,
the process will involve complex project coordination and logistics. To
learn from their international partners, CISA will be holding an
international risk management workshop this summer.

Dr. Klein continued by providing an update on the CDC Thimerosal
studies. The Vaccine Safety Datalink Screening Analysis was published in
*Pediatrics* in November 2003. The analysis showed there was no increase
in risk for autism or ADD. The subsequent studies will include a
follow-up neuropsychological testing study of children, a follow-up
study of vaccine trial participants, and a case-control study of
thimerosal and autism, which is currently being planned.

**Vaccine Management Business Improvement Project - Ms. Kimberly S.
Lane**

Ms. Lane presented background information on NIP. NIP administers \$1.2
billion in childhood vaccines and covers vaccine purchase funds and all
associated costs, such as vaccine ordering, vaccine order approval,
distribution, inventory management, and funds management. This is all
done through a combination of the VFC program and the 317 program. One
of the overarching goals of the program is to drive high levels of
childhood vaccination by ensuring an adequate vaccine supply, efficient
distribution, and emergency stockpiles.

The program has been very successful, but there are shortcomings. There
is minimal integration among supply chain partners (e.g., manufacturers,
NIP, states), which limits inventory visibility and reduces our ability
to manage it. An example of this is in vaccine shortage. There are
44,000 sites receiving vaccines through the program and trying to find
where we spot shortages has to be a manual process.

Ms. Lane added that the administrative processes are largely manual and
overly complex. There are 64 unique accounts set up at CDC based on a
really old 317-legacy system. One grantee receives 600 faxes per week
while another receives 200 per week, which is very burdensome and
duplicates many efforts.

NIP will partner with Booz Allen Hamilton, a private company with
commercial expertise in supply chains, distribution, as well as
government operations. They will be looking for ways to improve
operations, with the overall goal of developing and implementing an
automated, seamless VFC vaccine management system. The project
deliverables include an overview of the existing distribution system and
administrative processes. Second and third would be a diagnostic of
performance "gaps" and improvements for the shared vision. The fourth
deliverable will be a recommendation on alternatives and an agenda for
moving forward, including initiatives to implement and manage work
streams.

Ms. Lane noted that this is an opportunity to improve the program and
perhaps free up some funding that can be redirected to other core public
health functions.

Mr. Hutchins presented data showing that the majority of vaccines under
the VFC program are distributed through private third-party providers.
Mr. Hutchins noted that 5% (fewer than 2,500) of the 44,000 providers
account for a third of the vaccines. This makes it difficult to take a
"one-size fits-all" approach, since there are a few providers with a
very large volume and several providers with a small volume.

The second set of data Mr. Hutchins presented showed that if stockpiles
were all in place, the system would be operating with 9 to 10 months of
inventory under the VFC program, representing an investment of over
\$875 million. Mr. Hutchins noted that he hopes to have the first set of
recommendations by the end of March and then turned the presentation
over to Ms. Lane.

**Project BioShield - Dr. Philip K. Russell**

Dr. Russell provide an update of the progress on Project BioShield since
last year. The proposal for the administration had three phases. One was
to provide official authority to the Secretary and Commissioner of FDA
for emergency use authorization of products that are in IND status at
the time of the emergency. Congressional action will determine the
execution of this proposal. The second component is to give additional
acquisition authority to NIH and NIAID to change the hiring authority
and some of the contractual capabilities that would give NIH more
flexibility for contracting for the R&D aspect of the bio-terrorism
approach. The third part is within the Office of Assistant Secretary for
Public Health Emergency Preparedness and is the acquisition phase. The
proposed legislation has been redrafted and has been passed in the
House, but not in the Senate. The Administration is working with Senate
leadership to get it passed. Dr. Russell commented that the legislation
is being held up by legislative obstacles.

Dr. Russell then addressed the potential procurements under
consideration. First is the rPA anthrax vaccine, because there is very
little of the vaccine in inventory. The next consideration is the
smallpox vaccine for high-risk individuals. There are 30 million to 50
million people in the U.S. for which the smallpox vaccine is
contraindicated, so a safer smallpox vaccine is a high priority.
Botulinum antitoxin (Equine) is a high priority because, of the threat
of the botulinum toxins in the milk/food supply. This is a familiar
program because according to CDC, the antitoxin can be processed from
immunized horses. Also under consideration are anthrax immune globulin
products, recombinant plague vaccine, replacement botulinum vaccine, as
well as a short list of anti-radiation drugs and chemical antidotes. The
legislation was extended beyond biological hazards and vaccines to
include chemical and anti-radiation antidotes.

Potential future candidates for BioShield procurement include the
Ebola-Marburg vaccine, Rift Valley Fever Vaccine, novel
antibiotic/anti-infective, novel antiviral, human anthrax and botulinum
antitoxins from transgenic animals, and possibly a third generation
anthrax vaccine. The need for an efficient vaccination against anthrax
is a very high priority. There needs to be a better way to deliver that
vaccine.

**Thimerosal/Autism Litigation**

**National Vaccine Injury Compensation Program -Ms. Elizabeth Saindon**

Ms. Saindon began by providing a background on the National Vaccine
Injury Compensation Program (NVICP). Established in 1986, it was
developed as a no-fault compensation scheme whereby persons allegedly
suffering injury or death as a result of the administration of certain
compulsory childhood vaccines may petition the federal government for
monetary damages. Congress intended that the Vaccine Program provide
individuals a swift, flexible, and less adversarial alternative to the
often costly and lengthy civil arena of traditional tort litigation.

Settlements are based on the Vaccine Injury Table, which summarizes the
adverse events caused by vaccines. Individuals and their families can
qualify for compensation in three ways. First is to show that an injury
found on the Vaccine Injury Table occurred in the appropriate time
interval following immunization. For injuries outside of the table, the
other two ways to qualify include proving that the vaccine caused the
condition or demonstrating that the vaccine worsened or aggravated a
pre-existing condition.

NVICP is jointly administered by DHHS, the United States Court of
Federal Claims, and DOJ. At the beginning of the program, almost all of
the claims were table claims. However, as the vaccine supply has
improved and become safer, the newer vaccine caused injuries are from
vaccines taken off the market. As a result, almost all of the cases are
now based on the foundation of fact. This has caused backlog in the
program.

In the middle of 1999, manufacturers began making certain vaccines
without thimerosal. In reaction to this, beginning in late 1999 and
2000, people began to sue the vaccine manufactures, alleging that the
mercury in the vaccine was causing autism. Because of the jurisdictional
issue, the civil courts first looked at the jurisdiction laagering
claim. The decision was made that all of the claims should go through
NVICP first because it was the vaccine itself that was at issue.
Beginning in July 2002, there were approximately 400 autism cases filed
with the NVICP. As of today, there are more than 3,500 cases, with more
being filed everyday.

In order to respond to this influx of cases, DOJ proposed a way of
dealing with the caseload. First, there is to be an inquiry into the
general causation issue, which looks at whether the vaccine caused
autism and under what circumstances. The second phase is to apply the
results of the first phase to the individual cases. That permits the
petitioners to come into the program by filing a one-page sheet of paper
saying that they want to join the autism proceedings; they are not
required to supply medical records. This short-form petition has caused
some litigation within the litigation.

A rigid schedule for discovery was imposed, with an end date of August
2003. Causation hearings are to be conducted March 2004, and a ruling on
causation is scheduled for July 2004. The discovery has been very
burdensome and as a result, the litigation is behind schedule. The
Office of Special Masters has permitted petitioners to seek discovery
from the department and there have been productions for essentially
every operating division. For the most part, the document discovery is
complete, but the product licensing agreements from FDA is still an
issue.

Although almost all of the discovery has been completed from the initial
set of interrogatories, petitioners are now in a position to expand the
scope of discovery. They are also seeking third-party discovery from
manufacturers, and there will be a hearing on this issue. Due to these
discovery disputes, the hearing has been indefinitely postponed.

For updates, she encouraged NVAC to visit the Office of Special Masters
section in the U.S. Court of Federal Claims at
[www.uscfc.uscourts.gov](http://www.uscfc.uscourts.gov/).

**Civil Litigation Update - Mr. Randolph Moss**

Mr. Moss noted that he is not counsel on record on any of these cases
and is not representing any official position on behalf of any of the
litigants. In the 1980s there was crisis relating to vaccines and
vaccine litigation. There were 200 lawsuits that were brought against
vaccine manufactures relating to DTP. In the face of that escalating
litigation, all but four manufacturers left the market. This created a
shortage of vaccines, prices went up, and compensation was haphazard. As
a result, Congress created NVICP. The goals of the program were to
provide prompt, efficient, and fair compensation to individuals who were
injured by vaccines, and to protect the vaccine supply by minimizing
litigation.

Over the past few years, the thimerosal litigation has raised questions
about those goals. The litigation is proceeding through various stages.
The first phase of the litigation was jurisdictional disputes,
specifically whether claims needed to be processed through the program.
The core operative feature of the program is that if an individual
alleges injury from vaccines, that individual must file a claim under
the program. If the results of the program as undesirable, that
individual can then go to the courts.

The first phase of the litigation raised the issue of whether
individuals had to file a claim under the program. As of the end of
2003, there were more than 350 lawsuits and 11 class action suits. Many
of the individual cases have been dismissed but many continue to be
filed. There is one unique case, the California Proposition 65 case,
dealing with warnings to consumers of certain chemicals used in
vaccines.

There have been different attempts to circumvent the NVICP. Under the
National Childhood Vaccine Injury Act, all claims of \$1,000 or more had
to be filed with through the program. To undermine this provision, class
actions were filed that contained millions of people, each with \$999
claims. Another issue is that there is an argument made that thimerosal,
which is a preservative added to vaccines, is an adulterant, since the
program does not cover adulterants. There has been a range of derivative
cases brought by parents or grandparents of children who are alleging
vaccine-related injury. Their argument is that the child has to file a
claim under the program, but that parents and grandparents do not. The
final class of cases has been medical monitoring cases where the
argument has been that they do not have to file with the program because
they have not sustained an injury yet.

Largely, the courts have rejected each of these theories. There have
been 36 separate cases, as well as a decision of the Special Masters,
concluding that the adulterant theory does not work, since thimerosal is
not an adulterant. Despite this, these cases continue to be filed. For
derivative cases, the courts have held that, to the extent that someone
is seeking compensation for medical expenses, these cases must be filed
under the program first. The \$1000-claims have been dismissed and all
of the class actions have been dismissed, though some are in appeal. The
California Proposition 65 case has been dismissed with prejudice on the
basis that federal law preempts state laws relating to the labeling of
vaccines. This case is on appeal.

There are many thousands of claims that are pending in the program and
the delay in discovery is a very serious issue. However, the real
question about the interaction between the program and litigation is
what is going to happen next. A major issue to come is whether the
claimants in the program will decide whether they want to accept the
judgment under the program or whether they will decide to opt out of
that process and decide to litigate. This process is already developing,
with 11 cases that are currently pending back in court. In general, the
courts have done a good job of sending these cases back to the program,
but there are still questions about what the next steps will be in light
of the breathtaking expenses.

**DHHS Agencies and Committees Reports**

**ACCV/DVIC Report - Ms. Jackie Noyes and Dr. Geoffrey Evans**

Ms. Noyes noted that they have been short on committee members and have
about two years of catch up to do. As a result, their March meeting will
consist of almost all new members. She is concerned about the viability
of the program and what its survival means to the childhood immunization
program. She noted there is legislation in Congress that will correct
many of the gaps in NVICP that has not yet moved. Congress was to get to
it in June of 2003 but did not. Additionally, influenza vaccine will be
added to NVICP in the future.

**VRPBAC/FDA Report -Dr. Norman Baylor**

Dr. Baylor shared that the VRPBAC meeting will be on February 18 and 19
at the Sheraton Four Points Hotel in Bethesda, Maryland. They will be
selecting the influenza vaccine strains for 2004--2005. They will also
discuss the use of tissue cultures in the manufacturing process of
vaccines. He announced that Dr. Overturf will be taking over the chair
of VRPBAC.

**ACIP/NIP Report - Dr. Stephen Cochi**

Dr. Cochi provided an overview of the NIP activities. He noted that
despite the challenges with vaccine supply shortages of Td, DTaP, PCV-7,
MMR, and varicella, the overall coverage levels have been the highest
the program has ever attained. Every one of the coverage levels is a
record high.

He then noted that the National Infant Immunization Week (NIIW), from
April 25 to May 1, 2004, will include all 38 countries in the Western
Hemisphere. CDC and the department are working with PAHO and the Mexican
government to support these advocacy events, including cross-border
activities in San Diego and El Paso. There is also some discussion of
doing this worldwide, perhaps as early as 2005. As part of NIIW, on
April 23, CDC will be participating with the March of Dimes in a media
event to celebrate the start of the 50^th^ Anniversary of the Start of
Polio Clinical Trials.

Dr. Cochi presented NIP's global GPRA targets. These include the
eradication of polio by 2005, the reduction of the annual global
measles-related mortality (compared with 1999 estimates of 875,000
deaths), and the elimination of ongoing indigenous measles transmission
in all 47 countries and territories of the Americas by 2005. The last
target was achieved in November 2002. There is also a new target to
eliminate rubella in the Americas by 2010.

**NIH - Dr. George Curlin**

Dr. Curlin mentioned two international clinical trials. One is just
getting started and one has just finished. They have completed the
immunizations in Gambia. They are just starting clinical trials in India
on bovine vaccine strains, which should be completed in 3 years. It is a
rigorous program and they will have a more detailed report in the
future.

**Public Comment**

Clare Hannon reiterated some ASTA and state concerns about the 317
funding cuts. She acknowledged that NVAC has been supportive. The
infrastructure funding is being cut by a little more than \$1 million,
as well as the vaccine purchasing funding. There is a movement towards a
two-tiered system where vaccines are covered by VFC and insurance, but
there is no funding in 317 to provide vaccines to the 12% served by 317.
On the infrastructure side, there is a good children's program that
needs to be sustained, but many states have only part-time coordinators
in adult programs. They are concerned that states are grappling with
budget deficits themselves. Down the road, the states may have problems
with their coverage and it may be hitting a certain group of children.

Dr. Peter suggested putting on the agenda for the next meeting a review
of the implications of 317 cuts.

**Adjournment**

Dr. Peter thanked all of the speakers and noted that he has never been
at a meeting with so much information. He thanked Carolin Commodore for
her support of the meeting and Dr. Gellin who put together the agenda.
Dr. Hinman noted that this is Dr. Peter's last meeting as chair and
thanked him for his leadership.

Dr. Peter adjourned the meeting.