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     NOVEMBER 20, 2008
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                 The Committee convened at 1:00
     p.m. via teleconference, John Modlin, M.D.,
 17  Acting Chair, presiding.
 19  JOHN MODLIN, M.D., Acting Chair
     SETH HETHERINGTON, M.D., Non-Voting Industry
     VICKY DEBOLD, Ph.D., R.N., Consumer
 22   Representative

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  1               A-G-E-N-D-A
  2  Open Session
  3  Call to Order . . . . . . . . . . . . . . 4
  4   John Modlin, MD, Acting Chair
  5  Administrative Matters . . . . . . . . . 4
      Christine Walsh, RN, FDA
     Presentation of Laboratory of DNA Viruses,
  7  Division of Viral Products, Office of Vaccines
  8  Research and Review, Center for Biologics
     Evaluation and Research
     Overview of Research/Site Visit Process,
 10  (CBER) . . . . . . . . . . . . . . . . . 10
      Carolyn Wilson, PhD, FDA
 12  Overview, Office of Vaccines Research and
     Review (OVRR), CBER . . . . . . . . . . 23
 13   Konstantin Chumakov, PhD, FDA
 14  Overview, Division of Viral Products (DVP),
     OVRR . . . . . . . . . . . . . . . . . . 34
 15   Jerry Weir, PhD, FDA
     Overview, Laboratory of DNA Viruses . . 46
 17   Philip Krause, PhD, FDA
 18  Q&A . . . . . . . . . . . . . . . . . . . 55
 19  Open Public Hearing . . . . . . . . . . . 58
 22  Adjournment . . . . . . . . . . . . . . . 62

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  1               P-R-O-C-E-E-D-I-N-G-S
  2               1:04 p.m.
  3              ACTING CHAIR MODLIN: Why don't we
  4  go ahead and call the meeting to order and I
  5  guess I turn things right back over to you for
  6  an announcement, right Christine?
  7              MS. WALSH: Okay, thank you. Good
  8  afternoon. I'm Christine Walsh, the
  9  Designated Federal Officer for today's
 10  teleconference meeting of the Vaccines and
 11  Related Biological Products Advisory
 12  Committee.
 13              I would like to welcome everyone
 14  to this meeting. Today's session will consist
 15  of presentations that are open and closed to
 16  the public as described in the Federal
 17  Register Notice of November 3, 2008. Of the
 18  committee members, Dr. Jackson is unable to
 19  attend today's meeting and we are waiting on
 20  Dr. Gilbert right now. I would now like to
 21  read into the public record the conflict of
 22  interest record - statement, I'm sorry - for

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  1  today's meeting.
  2              The Food and Drug Administration
  3  is convening today's meeting of the Vaccines
  4  and Related Biological Products Advisory
  5  Committee under the authority of the Federal
  6  Advisory Committee Act (FACA) of 1972. With
  7  the exception of the industry representative,
  8  all members of the committee are special
  9  government employees (SGEs) or regular federal
 10  employees from other agencies and are subject
 11  to federal conflict of interest laws and
 12  regulations. The following information on the
 13  status of this advisory committee's compliance
 14  with federal conflict of interest laws,
 15  including but not limited to 18 U.S.C.
 16  208(n)(712) of the Federal Food, Drug and
 17  Cosmetics Act are being provided to
 18  participants in today's meeting and to the
 19  public.
 20              FDA has determined that members of
 21  this advisory committee are in compliance with
 22  federal ethics and conflict of interest laws.

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  1  Under 18 U.S.C. 208, applicable to all
  2  government agencies, Congress has authorized
  3  FDA to grant waivers to special government
  4  employees and regular government employees who
  5  have financial conflicts when it is determined
  6  that the agency's need for a particular
  7  individual's services outweighs his or her
  8  potential financial conflict of interest.
  9  Under ^U 712 of the Food, Drug and Cosmetics
 10  Act, Congress has authorized FDA to grant
 11  waivers to special government employees and
 12  regular government employees with potential
 13  financial conflicts when necessary to afford
 14  the committee their essential expertise.
 15              Today's agenda includes updates of
 16  the research program in the Laboratory of DNA
 17  Viruses, Division of Viral Products, Center
 18  for Biologics Evaluation and Research, FDA.
 19  Based on the agenda, it has been determined
 20  that the committee discussion presents no
 21  actual or appearance of a conflict of interest
 22  for today's meeting. Dr. Seth Hetherington is

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  1  serving as the industry representative acting
  2  on behalf of all related industry and is
  3  employed by Icagen, Inc.
  4              Industry representatives are not
  5  special government employees and do not vote.
  6  This conflict of interest statement will be
  7  available for review at the registration
  8  table. We would like to remind members that
  9  if the discussions involve any other products
 10  or firms not already on the agenda for which
 11  an FDA participant has a personal or imputed
 12  financial interest, the participants need to
 13  exclude themselves from such involvement and
 14  their exclusion will be noted for the record.
 15  FDA encourages all other participants to
 16  advise the committee of any financial
 17  relationships that you may have with firms
 18  that could be affected by the committee
 19  discussion.
 20              That ends the reading of the
 21  conflict of interest statement and Dr. Modlin,
 22  I turn the meeting back over to you.

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  1              ACTING CHAIR MODLIN: Christine,
  2  thank you. I think we'll begin by asking each
  3  of the members of the advisory committee to
  4  introduce themselves and where they're from
  5  and then we'll get started. I'll start. It's
  6  John Modlin from Dartmouth Medical School.
  7  I'm serving at this meeting as the Acting
  8  Chair of the advisory committee. Not
  9  everybody at once.
 10              DR. STAPLETON: My name is Jack
 11  Stapleton. I'm at the University of Iowa.
 12  I'm the Director of the Division of Infectious
 13  Diseases.
 14              DR. ROMERO: Jose Romero, from
 15  University of Arkansas from Medical Sciences,
 16  Arkansas's Children's Hospital Division of
 17  Pediatric Infectious Diseases.
 18              DR. SANCHEZ: Pablo Sanchez. I'm
 19  at UT Southwestern Dallas, Pediatric
 20  Infectious Diseases and Neonatology.
 21              DR. DESTEFANO: Frank DeStefano,
 22  RTII of Atlanta.

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  1              DR. DEBOLD: I'm Vicky Debold.
  2  I'm with the National Vaccine Information
  3  Center, Director of Patient Services.
  4              DR. HETHERINGTON: Seth
  5  Hetherington, Senior Vice President of
  6  Clinical and Regulatory Affairs at Icagen.
  7              MS. WALSH: Is there anyone else?
  8              DR. GILBERT: Peter Gilbert. I'm
  9  a Professor of Biostatistics at University of
 10  Washington and I'm at the Fred Hutchinson
 11  Cancer Research Center.
 12              MS. WALSH: Thank you, Dr.
 13  Gilbert. This is Christine. I just want to
 14  welcome you to the committee. This is Dr.
 15  Gilbert's first meeting with us. Welcome
 16  aboard.
 17              DR. GILBERT: Thank you.
 18              DR. DEBOLD: Welcome, Dr. Gilbert.
 19              ACTING CHAIR MODLIN: Do we have
 20  anyone else? If not, Dr. Gilbert, let me add
 21  my welcome to the committee. We'll go ahead
 22  and get started. The purpose of the meeting

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  1  today is to review the site visit report for
  2  the site visit for the Intramural Research
  3  Program and specifically the Laboratory of DNA
  4  Viruses in the Division of Viral Products,
  5  OVRR, as Christine had mentioned. We have
  6  three hours to conduct the review. I don't
  7  believe it's going to take anywhere near that
  8  amount of time, but at least we do have the
  9  time to, I believe, take a somewhat careful
 10  and a reasonable approach to this. I'm going
 11  to begin by turning things over to Dr. Carolyn
 12  Wilson from the FDA who will give us the
 13  overview of this site visit process. Dr.
 14  Wilson?
 15              DR. WILSON: Thank you and welcome
 16  to the advisory committee. And I want to
 17  start by thanking the members of the site
 18  visit committee who came and did the site
 19  visit of the laboratory. My talk is going to
 20  focus on an overview of how CBER views
 21  research in fulfilling its regulatory mission
 22  combined with how we manage our research

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  1  resources and finish with some specific
  2  information that the site visit needed to
  3  consider in its writing of the report and that
  4  would be helpful background for you all to
  5  consider as well.
  6              So to start on the second slide,
  7  CBER's mission is to ensure the safety,
  8  purity, potency and effectiveness of
  9  biological products, including vaccines, which
 10  is obviously the topic most relevant to
 11  today's review for the prevention, diagnosis
 12  and treatment of human diseases, conditions or
 13  injury.
 14              The next slide is the vision,
 15  which is to protect and improve public and
 16  individual health in the U.S., and where
 17  feasible globally, facilitate development,
 18  approval and access to safe and effective
 19  products, in harnessing new technologies and
 20  to strengthen CBER as a preeminent regulatory
 21  organization for biologics. And underlying
 22  all of these points is that we are very

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  1  actively engaged in keeping on top of
  2  innovative technology and applying it where
  3  feasible to advance public health.
  4              So, on the next slide if you're
  5  using animation you'll see that CBER's
  6  approach to regulation is that obviously we
  7  work under the laws of the Food, Drug and
  8  Cosmetics and Public Health Service Acts
  9  combined with regulations that are promulgated
 10  from those laws, but underneath of that we use
 11  a variety of tools, such as external
 12  discussion, active research at CBER, review of
 13  data submitted to the IND, as well as internal
 14  CBER discussion, and the point here is that
 15  the research is a critical component for - I
 16  don't know if you have that drumroll on yours
 17  or not - rational policy and decisionmaking.
 18              So that the point is that the
 19  research is critical for us to be able to
 20  fulfill our mission. And the way we do this
 21  is by having individuals that we call
 22  researcher regulators. These are

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  1  approximately 10 percent of our entire CBER
  2  staff and these are integrated into research
  3  and review activities. They do all the same
  4  type of review activities that a full-time
  5  reviewer would do, which includes review of
  6  INDs, BLAs, going on inspections, writing
  7  guidance documents, developing policy and also
  8  making presentations and organizing advisory
  9  committee meetings.
 10              And the point here is that because
 11  these research scientists are actively engaged
 12  in the review process they have an
 13  understanding of the relevance of how their
 14  expertise can be applied in a timely and
 15  useful way.
 16              So in the next slide is an
 17  overview of how we manage our research
 18  resources. And we start - it's really a
 19  cyclical thing, but we'll start on Number 1,
 20  which is to first look at what are our
 21  regulatory and public health needs, and that's
 22  looking both in-house and what our current

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  1  portfolio of regulatory work involves as well
  2  as what we call "horizon-scanning." Looking
  3  ahead, what are the products that are likely
  4  to be coming to us in the near future and how
  5  do we prepare for those? A lot of them have
  6  very challenging scientific issues that they
  7  bring with them.
  8              And from that we derive our
  9  center-wide research priorities and from that
 10  each office then looks again at their own
 11  internal portfolio and aligns their research
 12  plans and priorities in line with the center-
 13  wide priorities. Research programs are then
 14  evaluated on an annual basis by management for
 15  their alignment with their office-based
 16  priorities as well as externally every four
 17  years with the site visit. And that's a
 18  critical component really of all these phases
 19  which is that we always are engaged with the
 20  outside to get external review and input on
 21  the relevance of our research as well as the
 22  quality and productivity.

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  1              So our FY08 research priorities
  2  which we're currently in the process of
  3  revising for `09, but since the site visit was
  4  done in `08 I think it's kosher to still show
  5  these, is first, to improve or develop new
  6  methods to measure and augment biological
  7  product quality, safety and efficacy; second,
  8  to evaluate, develop and integrate novel
  9  scientific technologies to improve biologics
 10  product regulatory pathways, availability and
 11  quality; and third, to facilitate development
 12  of new biological products for high-priority
 13  public health threats, including pan-flu,
 14  emerging infectious disease and agents of
 15  bioterrorism.
 16              And I won't read through the last
 17  three. They're equally important, but they
 18  aren't relevant to today's group that we're
 19  reviewing. These are more related to
 20  biostatistics and epidemiology.
 21              So in the last half of my talk I
 22  wanted to just review some of the definitions

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  1  about our staff so that as you're discussing
  2  each of the personnel and what kind of actions
  3  you're recommending for them you understand
  4  exactly what we're talking about when we use
  5  certain terms.
  6              So the first set of terms I'm
  7  going to review are those that we considered
  8  permanent staff members. And we use the lingo
  9  "converted" or "permanent," but in academic
 10  lingo it's the equivalent of tenured. The
 11  first group is senior investigators. These
 12  are independent research regulators with
 13  assigned resources and support staff. The
 14  second group are staff scientists. These are
 15  support scientists who work under a senior
 16  investigator and they don't have any
 17  independent resources of their own. Both
 18  groups of scientists are evaluated for cyclic
 19  review for progress or in some cases for
 20  promotion to the next grade level.
 21              The second group are what we call
 22  service fellows. These are non-permanent

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  1  staff members, in other words not converted or
  2  what in academia would be called tenure-track.
  3  So there's one group which is what's called a
  4  senior staff fellow or a visiting associate,
  5  and these are up to 7-year appointments to
  6  demonstrate the potential for conversion to a
  7  senior investigator.
  8              So these are people who are
  9  independent scientists who are trying to
 10  demonstrate their ability to work
 11  independently and in an area that's of
 12  relevance to CBER, and also to be doing high-
 13  quality productive science. The staff fellow
 14  or visiting associate is a 4-year support
 15  position. It's equivalent more or less to a
 16  postdoctoral fellow. They have the potential
 17  to be extended up to an additional three years
 18  and may be considered for conversion to a
 19  staff scientist position.
 20              So again, these are support
 21  scientists who do not have their own
 22  resources. And these individuals are

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  1  evaluated through the site visits for final
  2  review as a service fellow as well as in some
  3  cases, depending on where in that 7-year cycle
  4  the site visit hits, it may be a cyclical
  5  review for progress.
  6              This next slide is a summary of
  7  sort of the career paths, and I want to thank
  8  Kosta Chumakov, actually, for drafting this
  9  very nice graphic because sometimes it is kind
 10  of confusing, but the idea is that we kind of
 11  have two parallel paths. One is a staff
 12  fellow or visiting associate that once they've
 13  had a successful site visit they go then for
 14  an internal review by our Promotion,
 15  Conversion and Evaluation committee, and if
 16  favorable may be converted to a staff
 17  scientist. And the other is senior staff
 18  fellow or visiting scientist which again - who
 19  needs to go through a successful - oops,
 20  hello?
 21              ACTING CHAIR MODLIN: Dr. Wilson,
 22  are you still with us?

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  1              DR. WILSON: Yes, can you hear me?
  2              ACTING CHAIR MODLIN: Yes, please
  3  continue.
  4              DR. WILSON: Okay, sorry. So -
  5              ACTING CHAIR MODLIN: Little
  6  technical -
  7              DR. WILSON: Okay, everybody's on
  8  board now?
  9              ACTING CHAIR MODLIN: Yes.
 10              DR. WILSON: Okay. So after a
 11  successful site visit and, again, internal
 12  review by our Promotion, Conversion and
 13  Evaluation Committee may be converted to a
 14  senior investigator.
 15              So the site visit team's
 16  assignment is to evaluate these individual
 17  principal investigators and service fellows in
 18  a laboratory unit - apologies for that typo of
 19  having "unit" twice. Their assignment is to
 20  look at the research accomplishments since the
 21  last review cycle as well as to evaluate the
 22  research proposals that would cover the work

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  1  for the next four years.
  2              And in the context of looking at
  3  this, we also ask the site visit to take into
  4  account that because these research scientists
  5  also have review work and assignments that
  6  they need to take into account the amount of
  7  time available to attend to the research. We
  8  welcome administrative or management comments
  9  in addition to scientific input if they are
 10  relevant.
 11              Okay, and the regulatory tab for
 12  these and regulatory work, while presented to
 13  provide a context for the scientific
 14  activities is not assessed per se by the site
 15  visit team, but the quality of regulatory work
 16  is assessed when these individual scientists
 17  are reviewed by the Promotion, Conversion and
 18  Evaluation committee.
 19              So we ask the site visit team to
 20  provide suggestions about whether or not an
 21  individual is on the right track, if not how
 22  would they get to the right track. We want

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  1  them to comment on the quality of the science,
  2  what research directions and approaches should
  3  be considered if they're not already, if
  4  there's additional laboratory expertise that's
  5  lacking to address the scientific problems and
  6  whether or not there are changes in laboratory
  7  organization or new collaborations that should
  8  be suggested.
  9              The draft report which is the
 10  subject of today's conversation is distributed
 11  to the full advisory committee by Dr. Freas'
 12  staff, and it's your task today to review that
 13  report and either approve it or send it back
 14  to the site visit team for revision. Once it
 15  is finalized, the center uses these reports in
 16  many ways.
 17              As I mentioned, it becomes a part
 18  of the package that goes for Promotion,
 19  Conversion and - for evaluation by the PCE
 20  committee for these personnel actions, the PIs
 21  read these reports very carefully and take
 22  into consideration the scientific suggestions,

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  1  and by management these are also used for
  2  making decisions about resources pending
  3  resource availability.
  4              So to just finish up then, when we
  5  do get to the point if a person has a
  6  favorable site visit and we want to put them
  7  forward for conversion or promotion, just so
  8  you understand that part of the process, they
  9  can be nominated by the division director or
 10  self-nominated, and a very detailed package
 11  goes for review by the PCE committee who then
 12  makes a recommendation to the center director.
 13              And I just wanted to finish with a
 14  quote from the FDA Science Board Subcommittee
 15  on Science and Technology that was submitted
 16  in November of last year that CBER has a
 17  rigorous process for establishing priorities
 18  and the impact of center research on
 19  regulation, and in addition that leadership
 20  insists upon integration of laboratory
 21  scientists both in the review and
 22  manufacturing site inspection process. And

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  1  the most important component here relevant to
  2  today is the external peer review of research
  3  programs is the norm rather than the
  4  exception. And so we really thank you for
  5  your time and effort and your input into this
  6  important process. Are there any questions?
  7  Okay, thank you.
  8              ACTING CHAIR MODLIN: Okay. No
  9  questions for Dr. Wilson? If not, we'll move
 10  on to the overview of the Office of Vaccines
 11  Research. Kosta Chumakov, you're up.
 12              DR. CHUMAKOV: All right, thank
 13  you John. All right, so I'll give the
 14  overview of the Office of Vaccines Research
 15  and Review, and the way research programs are
 16  managed here. So the mission of the office is
 17  to regulate protective vaccines and we do it
 18  by review of regulatory submissions as well as
 19  conducting intramural research here in our
 20  office.
 21              So the next slide shows you a
 22  structure of the office, and I must say that

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  1  there are several mistakes here because the
  2  structure is undergoing changes, especially in
  3  the Division of Vaccines and Related Products
  4  Applications. So there are two product
  5  offices that conduct intramural research. The
  6  first one is the Division of Bacterial,
  7  Parasitic and Neurogenic Products and the
  8  second one is Division of Viral Products which
  9  is the subject of today's review. They also
 10  have two offices, Division of Vaccines and
 11  Related Products Applications that deal
 12  exclusively with regulatory review of
 13  submissions as well as the recently
 14  established Division of Product Quality the
 15  goal of which is to ensure quality and quality
 16  assurance and quality control of vaccines.
 17              So the goal of your research
 18  program is to - next slide, Number 3 - is to
 19  develop approaches for evaluation and
 20  improvement of safety and efficacy of
 21  vaccines. We'll also do development and
 22  validate reference materials needed for

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  1  assessment of vaccine quality. Important part
  2  of our research mission is identifying new
  3  pathways for regulatory evaluation of vaccine
  4  product, especially new, innovative vaccines
  5  that are coming on the market. And the
  6  overarching goal, it is last but not the
  7  least, is to maintain scientific expertise of
  8  the office staff. So next slide.
  9              As Dr. Wilson already described,
 10  CBER uses what we call researcher reviewer
 11  model which means that scientists performing
 12  initiate - investigator-initiated research are
 13  also personally involved in review of
 14  regulatory submissions which provides them
 15  with the unique outlook on the issues that
 16  they address in their research programs.
 17              So the unit of our research
 18  program - and next slide please, Number 5 - is
 19  the research group which is led by a principal
 20  investigator. It's a senior scientist that
 21  leads a group of support staff and fellows
 22  that conduct research, and this is -

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  1              ACTING CHAIR MODLIN: I'm sorry,
  2  John, there's something interfering
  3  periodically with your presentation. It
  4  sounds like someone's rustling papers or
  5  something, but I'd just encourage everybody to
  6  put their phones on mute unless they have
  7  something to say and then we'll continue on.
  8  Thanks.
  9              DR. CHUMAKOV: All right. So our
 10  principal investigators are selected after a
 11  nationwide search and they undergo tenure-
 12  track evaluation and then put on permanent
 13  staff. So together with the principal
 14  investigator there are often scientists who
 15  are not independent which means that they work
 16  on assignments given by their principal
 17  investigator. So there are also technicians
 18  who are either biologists, microbiologists, or
 19  chemists and our junior research staff which
 20  is hired through our contract mechanism which
 21  we call ORISE Fellows. So as of the end of
 22  last fiscal year OVRR had about 30 principal

      Page 27
  1  investigators, 10 staff scientists, there was
  2  also five senior staff fellows who were on
  3  track to become principal investigators, 39
  4  staff fellows and visiting associates who
  5  potentially then can be considered for
  6  conversion into staff scientist position as
  7  well as 82 ORISE Fellows working together with
  8  their PIs. So slide Number 7.
  9              As you know, two years ago OVRR
 10  was reviewed by a site visit and one of the
 11  recommendations was that the office should
 12  develop a more comprehensive strategic plan of
 13  research management and identification of
 14  important issues to address in the intramural
 15  program.
 16              So in response to this suggestion,
 17  office established a research management
 18  committee that consists of the Associate
 19  Director for Research, Management and
 20  Scientific Affairs as well as division
 21  directors and their deputies from two product
 22  offices, bacterial and viral products, and

      Page 28
  1  also directors of regulatory offices in
  2  regulatory division and Division of Product
  3  Quality. And there are also representatives
  4  from each of the divisions that are either
  5  principal investigators or staff scientists
  6  who kind of do have a representation from all
  7  levels of research management.
  8              And the goal of this management
  9  committee - next slide, please - is first to
 10  set office research priorities and to ensure
 11  that investigator-initiated research addresses
 12  these priorities which is very important
 13  because of course there are issues that are
 14  coming from our regulatory work, but on the
 15  other hand we still maintain the time-tested
 16  investigator-initiated research model, and to
 17  ensure that these two concepts work well
 18  together we need to devise special mechanisms
 19  of communication within the office.
 20              Of course, it's important also to
 21  maintain uniformity because the research is
 22  conducted in different offices and we must

      Page 29
  1  make sure that all the procedures are
  2  equitable across the office. And of course,
  3  it's very important to make sure that those in
  4  OVRR staff that do not perform their own
  5  research on the bench should also be able to
  6  communicate priorities and ideas that they can
  7  gather from regulatory work to those who can
  8  implement these ideas in the laboratory
  9  research.
 10              So here is a next slide, I think
 11  it's next to the last at least for OVRR
 12  research priorities that were based on the
 13  wider CBER priorities. So the first addresses
 14  development of new methods and concepts that
 15  enhance safety of vaccines and related
 16  products. The second one addresses the issues
 17  of efficacy of vaccines. The third priority
 18  is special emphasis of new biological products
 19  that are addressing high-priority public
 20  health threats, including counter-terrorism
 21  activities as well as emerging diseases and
 22  pandemic influenza issues. And finally, we

      Page 30
  1  also consider work on the new technologies
  2  that open new regulatory pathways also a very
  3  high priority.
  4              So, finally on the last slide
  5  there is a chart that illustrates the research
  6  management process. As I already mentioned,
  7  we have this research management committee
  8  that serves as a hub for communications
  9  between PIs on the bench and the regulatory
 10  scientists in the review divisions.
 11              So first we identify priorities
 12  and they are being communicated to principal
 13  investigators who also synthesize all this
 14  information based on the current regulatory
 15  issues that they identify themselves in the
 16  course of their review activity, also site
 17  visit recommendations, advisory committee
 18  recommendations, interactions with their peers
 19  in academia, et cetera, et cetera. So after
 20  our principal investigator digests all this
 21  information, he or she proposes a plan for the
 22  next year research plan. And this is

      Page 31
  1  communicated through a lab chief and there is
  2  a feedback, there is a discussion between each
  3  principal investigator and lab chief, and the
  4  opportunity to adjust the next year plans.
  5  And then the same process continues from the
  6  level of division director and lab chief.
  7              So, finally division directors
  8  collate all this information and combine all
  9  the proposals coming from principal
 10  investigators and their division-wide research
 11  plan, and this portfolio is submitted back to
 12  a research management committee that meets for
 13  the second time during the fiscal year cycle
 14  and reviews all the proposals from both
 15  divisions and also has an opportunity to
 16  provide feedback to principal investigators
 17  and everybody else involved and submit the
 18  overall annual office research plan to the
 19  senior management in the office and later it
 20  goes to the center level for budget
 21  allocation. So this is basically how research
 22  is managed in the office and this concludes my

      Page 32
  1  presentation. I'm ready to take any
  2  questions.
  3              ACTING CHAIR MODLIN: Kosta,
  4  thanks very much. Are there questions for Dr.
  5  Chumakov?
  6              DR. DEBOLD: I have one question.
  7  This is Vicky Debold.
  8              DR. CHUMAKOV: Yes.
  9              DR. DEBOLD: Can you tell me where
 10  the work is done? I'm looking at that second
 11  slide of yours where you said that there were
 12  some updates that needed to be made to it. Is
 13  there a particular place in the organization
 14  where research on adjuvants is done, or is
 15  that handled with specific vaccines as opposed
 16  to adjuvants as a group?
 17              DR. CHUMAKOV: No, we don't have
 18  an organizational unit that addresses the
 19  adjuvants. Research on adjuvants is conducted
 20  in different labs. And no organizational
 21  structure can capture the complexity, you
 22  know, multi-layer issues that we address. So

      Page 33
  1  I mean, it's a continued work in progress. As
  2  the research evolves, I mean, some of the
  3  laboratories are combined and often
  4  laboratories emerge based on the emerging
  5  issues.
  6              And since the issues with
  7  adjuvants are coming to the forefront, I mean
  8  it is possible that there will be some
  9  adjustment in the future. So the structure is
 10  in the flux and - but no, to specifically
 11  answer your question, there is no single
 12  organizational unit that deals with adjuvants.
 13  It's spread in different labs.
 14              ACTING CHAIR MODLIN: Thank you,
 15  and maybe I could follow up is, it's certainly
 16  fair to say that in the process of
 17  responsibilities with the entire office for
 18  conducting regulatory reviews is that both the
 19  safety and the intergenicity of the other
 20  issues regarding effectiveness of each
 21  individual product are examined in explicit
 22  detail. I just wanted to emphasize that for

      Page 34
  1  the record. Are there any other questions for
  2  Dr. Chumakov?
  3              MS. WALSH: This is Christine. I
  4  just wanted to remind all the members, if you
  5  do have a question if you could please
  6  identify yourselves in the beginning. We do
  7  have a transcriber in the room who needs to
  8  know who is speaking. So thank you very much
  9  for that.
 10              ACTING CHAIR MODLIN: That was
 11  John Modlin. Pardon the oversight. Our next
 12  speaker is Dr. Jerry Weir who is going to give
 13  us an overview of the Division of Viral
 14  Products. Jerry?
 15              DR. WEIR: Thanks, good afternoon.
 16  I thank everyone for coming. I'm going to
 17  give a brief overview. A lot of you have
 18  probably heard some version of my presentation
 19  of this in the past so I'll try to be brief as
 20  well. If you flip to the second slide it
 21  gives the organizational structure of the
 22  Division of Viral Products.

      Page 35
  1              There's seven laboratories roughly
  2  arranged along product lines. I'm the
  3  director, Phil Krause is the deputy director.
  4  The seven labs are named the Laboratory of
  5  Hepatitis Viruses, the Laboratory of DNA
  6  Viruses, Laboratory of Respiratory Viral
  7  Diseases, the Laboratory of Immunoregulation,
  8  the Laboratory of Vector-borne Viral Diseases,
  9  the Laboratory of Retrovirus Research, and the
 10  Laboratory of Method Development.
 11              Since we had this site visit in
 12  April we've had a few changes. Andy Lewis,
 13  the lab chief of DNA Viruses, asked to be
 14  relieved of his administrative and managerial
 15  responsibilities and we've accommodated that
 16  request for the time being with Phil Krause
 17  taking over those responsibilities in the
 18  laboratory. Andy of course remains principal
 19  investigator in his lab. You've also heard
 20  Konstantin Chumakov give the overview for the
 21  Office of Vaccines. He's now acting as the
 22  Associate Director for Research. So we're all

      Page 36
  1  sort of wearing several hats for the time
  2  being.
  3              The next slide shows a very brief
  4  statement of our mission and functions in the
  5  Division of Viral Products. It's pretty
  6  simple. We regulate viral vaccines and
  7  related biological products and ensure their
  8  safety and efficacy for human use and we try
  9  to facilitate the development, evaluation and
 10  licensure of new viral vaccines that
 11  positively impact the public health. To do
 12  that we're engaged in many different
 13  activities.
 14              As you see on the next slide, I've
 15  listed some of these here. We are involved in
 16  investigational new drug application review,
 17  biologics license application or BLA and
 18  supplement review. We're involved in lot
 19  release review and actually no longer involved
 20  in lot release testing. That's actually
 21  something I need to update on the slide, but
 22  we do still participate in lot release review

      Page 37
  1  and sign-off. We're involved in different
  2  post-marketing activities, for example
  3  biological product deviations. The division
  4  participates extensively in manufacturing
  5  inspections and we have an extensive role in
  6  consultation with other public health agencies
  7  such as WHO, CDC and NIBSC in the UK.
  8              Last but not least, in the next
  9  slide we conduct a research program to support
 10  our regulatory mission. The type of research
 11  activities can span the spectrum from the very
 12  basic to the very applied. They cover
 13  different things throughout the division
 14  including viral pathogenesis, vaccine safety
 15  and efficacy, including cell substrates,
 16  vaccine and viral vector evaluation.
 17              We have studies on correlates to
 18  identify correlates of protection. We're also
 19  still involved with reagent preparation
 20  exercises, particularly for influenza vaccines
 21  and pandemic flu vaccines. We have studies on
 22  methods development and evaluation and of

      Page 38
  1  course we're responsible for addressing
  2  emergent issues. Some of the ones in the last
  3  few years that we've addressed include BSE,
  4  counter-terrorism and of course pandemic
  5  influenza. The next slide shows a brief
  6  summary in a graph form of the staff of the
  7  Division of Viral Products.
  8              We've been fairly static over the
  9  years. We're hovering around 70 full-time
 10  equivalents now. That's the full-time
 11  equivalents that we have. We also in addition
 12  have probably more like 50 contract employees,
 13  mainly administer to the OIs program. A lot
 14  of these are postdocs and other technicians
 15  that are hired through this program. At any
 16  time the total staff of the division is
 17  somewhere around 120 individuals.
 18              The next slide shows a graph of
 19  some of our - just a brief snapshot of our
 20  budget situation. I haven't updated it for
 21  2008. You can see that at this point in time
 22  the external funds that we bring in to support

      Page 39
  1  our research sort of dwarf the amount of
  2  internal funds, and in the past year including
  3  in 2008 the division has brought in over $5
  4  million in outside contracts and grants. The
  5  internal budget which supports of course most
  6  of our basic operating work and the things
  7  that go on throughout the division has
  8  actually increased in the last year or two.
  9  This past year and in 2007 we had an internal
 10  budget of over $2 million.
 11              Numbers like these have actually
 12  not been seen - it's not on your graph, but
 13  have actually not been seen since 1995 or
 14  1996. So the last couple of years have been
 15  a little better for us in terms of operating
 16  monies than some of the early part of this
 17  decade were. But in any case, the take-home
 18  message here is that the staff and the
 19  division bring in a lot of outside funds and
 20  I think this is a good example of their
 21  competitiveness and the quality of their
 22  research programs.

      Page 40
  1              Okay. So today of course you're
  2  here to get the site visit report for the
  3  Laboratory of DNA Viruses. I'm not going to
  4  belabor this. Phil's going to give you a
  5  little overview of the lab itself. I've
  6  listed in this slide the actual teams. There
  7  are four principal investigators in this
  8  laboratory. One is - and the titles of their
  9  programs are listed on this slide. Andrew
 10  Lewis is a principal investigator and team
 11  leader and works in the development of assays
 12  that define sensitivity for the regulatory
 13  management of novel cell substrate. Phil
 14  Krause has his laboratory in this laboratory
 15  and the title - his research - getting
 16  feedback somewhere. Okay, can everyone still
 17  hear me?
 18              (Whereupon, the foregoing matter
 19  went off the record at 1:41 p.m. and went back
 20  on the record at 1:44 p.m.)
 21              MS. WALSH: Okay. We apologize
 22  for the interruption. Dr. Weir will continue.

      Page 41
  1              DR. WEIR: I was winding down
  2  anyway, but the - with the description of the
  3  four teams. As I said, one is run by -
  4  directed by Andy Lewis, the second one by Phil
  5  Krause concerning with DNA virus vaccine
  6  safety issues. Michael Merchlinsky is a team
  7  leader and his work concerns the development
  8  and evaluation of new generation smallpox
  9  vaccines. And my laboratory is also in this
 10  lab. It's concerned with DNA virus vaccines
 11  and vectors. The - next slide.
 12              The type of regulatory
 13  responsibilities that are addressed by this
 14  laboratory include smallpox vaccines, herpes
 15  virus vaccines, cell substrate issues, and
 16  like many other laboratories in the division
 17  now we've split up influenza virus vaccine
 18  regulatory work because of the workload that's
 19  involved in that subject matter now.
 20              The areas of research that are
 21  covered by the laboratory include the
 22  development and evaluation of new generation

      Page 42
  1  smallpox vaccines, safety concerns associated
  2  with cell substrates including detection of
  3  adventitious agents, the use of neoplastic
  4  cells, the development and evaluation of
  5  herpes virus vaccines and the development of
  6  methods to detect extraneous agents in
  7  vaccines.
  8              And the last slide just summarizes
  9  the site visit evaluation of April 3. The
 10  committee reviewed the research programs in
 11  this laboratory, they evaluated the progress
 12  of individuals in each research team and
 13  assessed the future directions of each
 14  research program. And that's all I have.
 15  Thank you for your time.
 16              MS. WALSH: Is everyone still
 17  there? This is Christine.
 18              DR. HETHERINGTON: Yes. Everybody
 19  is still here.
 20              DR. DEBOLD: Did we lose Dr.
 21  Modlin?
 22              MS. WALSH: Dr. Modlin?

      Page 43
  1              ACTING CHAIR MODLIN: How about
  2  that.
  3              MS. WALSH: Dr. Modlin, are you
  4  there?
  5              ACTING CHAIR MODLIN: Yes, I am.
  6              MS. WALSH: Okay.
  7              ACTING CHAIR MODLIN: I'm sorry, I
  8  think I had my button on mute. I apologize.
  9              MS. WALSH: Okay, that's all
 10  right.
 11              ACTING CHAIR MODLIN: But are
 12  there - again, are there any questions for Dr.
 13  Weir?
 14              DR. DEBOLD: This is Vicky Debold
 15  again. I just have a general question. I
 16  wasn't aware that the FDA staff was receiving
 17  grants external to the agency. Can you give
 18  me some idea of the funding mechanisms for
 19  their external grants?
 20              DR. WEIR: Can you hear me?
 21              DR. DEBOLD: Yes.
 22              DR. WEIR: Okay. Sure, I can give

      Page 44
  1  you a little bit and I think Carolyn Wilson
  2  could give you an even better overview. We
  3  have several mechanisms, but they don't for
  4  all practical purposes include R01s from NIH.
  5  We have other places like the Department of
  6  Defense, the National Vaccine Program Office
  7  and there are private organizations that will
  8  support research here. I don't know, Carolyn,
  9  you want to elaborate any more?
 10              DR. WILSON: So in terms of the
 11  exact mechanisms. If the sources of funding
 12  is coming from another government agency then
 13  that would be typically transferred through an
 14  interagency agreement, and in those cases
 15  where we are receiving funds from private
 16  granting organizations we use the
 17  Collaborative Research and Development
 18  Agreement in order to review those for
 19  conflict of interest and that's the mechanism
 20  by which we receive those funds.
 21              DR. BAYLOR: This is Norman
 22  Baylor. I just want to add here that we don't

      Page 45
  1  receive funds from the regulated industry. We
  2  cannot. We're prohibited from receiving funds
  3  from the regulated industry.
  4              DR. DEBOLD: I'm sorry, I'm having
  5  trouble hearing that. Norm, you need to speak
  6  up a little bit.
  7              DR. BAYLOR: Okay, I'm right over
  8  the mic. How about now?
  9              DR. DEBOLD: Better.
 10              DR. BAYLOR: Okay. I was just
 11  adding that we don't receive funds nor are we
 12  allowed to receive funds from the regulated
 13  industry. I just wanted to make sure that was
 14  clear.
 15              ACTING CHAIR MODLIN: Thanks. Dr.
 16  Debold, any other questions? Does anyone have
 17  any further questions?
 18              DR. DEBOLD: No, thank you.
 19              ACTING CHAIR MODLIN: Okay. If
 20  not, why don't we move on to Dr. Krause's
 21  presentation, and this will be the overview of
 22  the Laboratory of DNA Viruses, Dr. Philip

      Page 46
  1  Krause.
  2              DR. KRAUSE: I'm Phil Krause. I'm
  3  the Acting Lab Chief of DNA Viruses. At the
  4  time of the site visit back in April Andy
  5  Lewis was the lab chief and so I'm going to
  6  present the slides that he actually presented
  7  in large part to the site visit committee when
  8  the site visit actually occurred. The Lab of
  9  DNA Viruses, as Dr. Weir told you, has four
 10  organizational units, a unit on cell
 11  substrates and adventitious agents with Andy
 12  Lewis as the principal investigator, a unit on
 13  viral gene expression with Jerry Weir as the
 14  principal investigator, a unit on pox virus
 15  biology with Mike Merchlinsky as the principal
 16  investigator and a unit on viral latency which
 17  I am the principal investigator.
 18              The Laboratory of DNA Viruses has
 19  a number of important regulatory
 20  responsibilities. The kinds of things that
 21  fall to our members include management and
 22  consultation on regulatory issues associated

      Page 47
  1  with DNA virus vaccines that are under
  2  development. We now have a large number of
  3  licensed DNA virus vaccines including the
  4  varicella vaccine for chickenpox, a zoster
  5  vaccine that was licensed in 2005, MMRV which
  6  is a combination vaccine that includes a
  7  varicella component, a smallpox vaccine and a
  8  papilloma virus vaccine.
  9              And then also because of the
 10  involvement of DNA viruses in many of these
 11  issues we ended up taking the lead on cell
 12  substrate and adventitious agent issues. And,
 13  as Dr. Weir pointed out, the influenza
 14  regulatory burden has been spread fairly
 15  uniformly across the division because there
 16  has been a lot of work there, and so some of
 17  that has fallen to our laboratory as well.
 18  And then, of course it's important then to
 19  maintain flexibility to accommodate these
 20  changing vaccine safety and efficacy
 21  priorities in DVP and that includes also the
 22  cell substrate-related issues associated with

      Page 48
  1  the shift in influenza vaccine manufacture
  2  from embryonated eggs to cell culture.
  3              The next slide summarizes the
  4  Laboratory of DNA Virus staff as it existed
  5  both at the time of the previous site visit in
  6  2004 and the site visit in 2008 and you can
  7  see the division there. As is perhaps not
  8  that surprising based on the data that Dr.
  9  Weir showed you, all of the laboratories
 10  contain combinations of FTE staff and non-FTE
 11  staff. In most cases the non-FTE staff is
 12  supported by outside funds. And then along
 13  the same lines if you go to the next slide you
 14  can look at the Laboratory of DNA Virus
 15  funding picture in Fiscal Year 2007 where in
 16  fact a large proportion of the funding for
 17  research into the Laboratory of DNA Viruses
 18  came from the outside.
 19              And you can see the sources of
 20  funding for the DNA virus lab was mostly the
 21  National Institute for Allergy and Infectious
 22  Diseases, with some money coming from BARDA

      Page 49
  1  and from the National Vaccine Program Office.
  2              This next slide just gives a few
  3  examples of Laboratory of DNA Virus
  4  accomplishments since the previous site visit,
  5  and this is not an exhaustive list, but that
  6  includes review of a very large number of
  7  INDS, IND amendments, master files and master
  8  file amendments. It actually also includes
  9  the review of a large number of manufacturing
 10  supplements which aren't even listed here. We
 11  participated in the licensure of the next-
 12  generation smallpox vaccine which is ACAM2000.
 13  We also participated in the zoster vaccine and
 14  in the MMRV pro-quad vaccine which we also
 15  licensed through this period. We presided
 16  over the first revision of the OVRR CBER cell
 17  substrate guidance document since 1993, and a
 18  draft version of that was put out in 2006, and
 19  the final version we hope will be issued soon.
 20  Members of the laboratory published or
 21  contributed to the publication of 39
 22  published, peer-reviewed papers, delivered a

      Page 50
  1  large number of talks, Dr. Lewis came up with
  2  27, but I think the actual number is quite a
  3  bit greater, at least five of which were as
  4  consultants to the WHO. Received grants and
  5  contracts as you've seen from NVPO, NIAID and
  6  BARDA which I think serves as an additional
  7  reminder of the quality of the work and the
  8  value of the work not only to CBER, but also
  9  to other government entities. And then
 10  members of the laboratory such as ad hoc
 11  members of various study sections as well for
 12  NIH.
 13              I'm just going to go through the
 14  four units briefly here and tell you a little
 15  bit about the main aims in their research
 16  programs. So the cell substrate and
 17  adventitious agent program, the aims - so the
 18  major project is actually called "Development
 19  of assays to define sensitivity for the
 20  regulatory management of novel cell
 21  substrates." So this program focuses really
 22  on cell substrate issues. And the three aims

      Page 51
  1  that Dr. Lewis' lab focuses on are assessing
  2  the potential risk of oncogenic activity of
  3  residual cell substrate DNA, polyomaviruses as
  4  adventitious agents, and the evolution of the
  5  neoplastic phenotype with a focus on Vero and
  6  MDCK cells. And you don't have to go very far
  7  back, in fact just to the very last advisory
  8  committee meeting to see the immediate
  9  relevance of this kind of work because in fact
 10  a lot of the scientific data that were
 11  presented to help the committee get through
 12  its deliberations in thinking about what to do
 13  about the use of MDCK cells in the manufacture
 14  of next-generation influenza vaccines in fact
 15  came from Dr. Lewis' lab. At the time of the
 16  site visit there had been nine publications
 17  since the previous site visit and of the
 18  laboratory members, Dr. Lewis, who is a
 19  principal investigator and at that time was
 20  the lab chief, was being reviewed for
 21  progress.
 22              The second unit that I'll describe

      Page 52
  1  is a unit on viral gene expression. Jerry
  2  Weir is the principal investigator and the
  3  project title there is "DNA virus vaccines in
  4  vectors." And the major aims there have been
  5  to evaluate the immune response to vaccination
  6  with smallpox vaccines, to evaluate immune
  7  response to HSV-2 antigens and immunization
  8  strategies to enhance response and to
  9  facilitate preparation and development of
 10  pandemic influenza vaccines, a project that
 11  Dr. Lewis' lab took on in 2006. This has also
 12  been a highly productive enterprise with 11
 13  publications since the previous site visit.
 14  Dr. Weir, who as you know is both a member of
 15  the laboratory and the division director, was
 16  being reviewed for progress. In addition, two
 17  members of the laboratory who had been staff
 18  fellows were being reviewed for conversion to
 19  staff scientists at some point in the next
 20  couple of years. Those are Clement Meseda and
 21  Falko Schmeisser.
 22              The third unit I'll describe is a

      Page 53
  1  unit on pox virus biology where Michael
  2  Merchlinsky is the principal investigator.
  3  The title of his laboratory research program
  4  is, "Development and evaluation of new
  5  generation smallpox vaccines," and the aims
  6  are to study and develop assays for appraisal
  7  of preclinical and clinical efficacy of
  8  smallpox vaccines, to study bioassay systems
  9  to evaluate the role of genes in protective
 10  immune response to smallpox vaccines, and to
 11  study viral genes that participate in the
 12  resolution of viral DNA replication
 13  intermediates. This has also been a highly
 14  productive endeavor and the research has
 15  contributed directly to the regulatory work on
 16  smallpox vaccines with 11 publications since
 17  2004. Dr. Merchlinsky was being reviewed for
 18  progress and Alonzo Garcia, a member of the
 19  laboratory, was being reviewed for potential
 20  conversion to staff scientist.
 21              And finally, the unit on viral
 22  latency is the unit that I direct. The title

      Page 54
  1  of the project is, "DNA virus vaccine safety
  2  issues, contamination and viral latency," and
  3  in our lab we focus really on two major
  4  issues, although we've done a few other things
  5  as well: herpes simplex virus latency and
  6  molecular methods for virus detection. And it
  7  was interesting to hear again at the most
  8  recent advisory committee presentations and
  9  discussion the recommendation of the advisory
 10  committee that we look into novel molecular
 11  schemes, including high-throughput sequencing
 12  for detecting viruses in contamination and to
 13  assure the safety of cell substrates. That in
 14  fact is exactly what we're doing, so I think,
 15  as is the case with all of the projects in all
 16  of these units, they're really very focused on
 17  where we see the regulatory work not only
 18  being, but also where it's going. We had
 19  eight publications since 2004 and have had a
 20  few more since. And I'm the principal
 21  investigator and also the deputy director of
 22  the division and was being reviewed for

      Page 55
  1  progress.
  2              So to summarize really is the
  3  Laboratory of DNA Viruses is very proud of
  4  what we've been able to accomplish over the
  5  past four years. We certainly look forward to
  6  the challenges of the next four years and
  7  really are very grateful to the advisory
  8  committee for its feedback and suggestions
  9  which we hope are going to help us to meet
 10  those challenges. So thank you very much.
 11              ACTING CHAIR MODLIN: Dr. Krause,
 12  thank you. Let me ask if there are specific
 13  questions for Dr. Krause. Maybe I could ask
 14  one. John Modlin. Dr. Krause, how much of
 15  the external funding that's coming through
 16  NIAID is actually bioterrorism-related
 17  compared to the rest of the external funding?
 18  And I guess correlated to that, or add-on
 19  would be what's your view of the future of
 20  bioterrorism funding for the laboratory going
 21  forward?
 22              DR. KRAUSE: So it's a mix. Some

      Page 56
  1  of this money has been bioterrorism-related.
  2  Some of the money actually was also more
  3  specifically related to cell substrate issues
  4  because NIAID recognized some years ago also
  5  the need to make sure that data were available
  6  to support changes in cell substrates for
  7  vaccines. And so they created a request for
  8  proposals and members of our division,
  9  including our lab, Dr. Lewis and myself as
 10  well as other investigators were able to
 11  compete successfully for some of that money.
 12  And as you correctly point out, a lot of those
 13  sources of external funding are dwindling as
 14  NIAID looks more closely at its budget. So in
 15  fact the funding for the cell substrates, last
 16  year was the final year and so Dr. Lewis and
 17  I are looking for other sources of external
 18  funding to continue that work. And some of
 19  the bioterrorism funding still exists, but
 20  it's been supporting some of the work from Dr.
 21  Weir and Dr. Merchlinsky's laboratory, but as
 22  you point out also with the increasing

      Page 57
  1  pressure on the entire federal budget, it's
  2  always a question of how long that will last.
  3              ACTING CHAIR MODLIN: Other
  4  questions or comments? Let me open this up
  5  and ask if there are questions of any of the
  6  presenters or anyone else that's present at
  7  OVRR. Hearing none, let me thank each of the
  8  speakers for both brevity and clarity. It's
  9  been an interesting hour. I guess the next
 10  thing, Christine, is to ask if there is anyone
 11  who wants to make a presentation during the
 12  open public hearing session of the meeting, is
 13  that correct?
 14              MS. WALSH: That's correct. Is
 15  there anyone in the room who would like to
 16  make a public comment? Dr. Modlin, I see no
 17  one.
 18              ACTING CHAIR MODLIN: So that
 19  means we can dispense with the boilerplate,
 20  right?
 21              MS. WALSH: Yes.
 22              ACTING CHAIR MODLIN: If that's

      Page 58
  1  the case, then I think that we will go into
  2  closed session at this point. Again, I'd like
  3  to thank all of the speakers and I take it
  4  that we here on the phone are just expected to
  5  stay on the line and wait for the room to be
  6  cleared and that you'll let us know when it
  7  is, is that correct Christine?
  8              MS. WALSH: Yes. If everyone
  9  could stay on the line and it'll just be a few
 10  moments until the room clears, and then once
 11  it does we'll go into closed session. I'll
 12  let you know who remains in the room with us
 13  so it'll just be a minute and we'll be right
 14  back.
 15              ACTING CHAIR MODLIN: Thank you.
 16              DR. GILBERT: This is Peter
 17  Gilbert. The window is closing to ask
 18  questions, but is Dr. Krause still there?
 19              ACTING CHAIR MODLIN: Please, go
 20  ahead Peter. Go ahead and get it in, yes.
 21              MS. WALSH: We'll bring him right
 22  back.

      Page 59
  1              DR. GILBERT: Okay. That window
  2  closed so quickly.
  3              MS. WALSH: Dr. Krause is back.
  4              DR. KRAUSE: I'm back. Sorry.
  5              DR. GILBERT: Okay. Yes, I
  6  thought I'd better ask this before we go into
  7  closed session. It's, you know, I don't know
  8  much about your lab, but when you have studies
  9  that take a relatively advanced, maybe it's a
 10  physical input of design or analysis, do you
 11  have statisticians as part of the LDV, or do
 12  you collaborate with statisticians?
 13              DR. KRAUSE: So in fact the -
 14  obviously CBER has a fairly large Office of
 15  Statistics and Epidemiology, and in fact one
 16  of the nice features that we've been able to
 17  set up here in the Office of Vaccines is one
 18  of those statisticians comes down here and
 19  sits in our main office one day a week and is
 20  available for consultation, has actually
 21  helped some of us out quite a bit in solving
 22  various statistical problems. Sometimes

      Page 60
  1  statistical issues can be solved in other ways
  2  too because a lot of our work is collaborative
  3  with other institutions and so sometimes
  4  statisticians in other institutions also play
  5  some role in helping us analyze our data. But
  6  we're very fortunate to have Lev Sirarda as
  7  the statistician who ends up really focusing
  8  on laboratory issues. I think it's a very
  9  nice synergy because he then also then - he
 10  also will do some review work on laboratory-
 11  related issues as well, and so he sees that
 12  not only from the perspective then of what the
 13  manufacturers do, but also from the
 14  perspective of some of the research work
 15  that's going on in the office.
 16              DR. GILBERT: Thank you.
 17              ACTING CHAIR MODLIN: Thanks very
 18  much. Any other questions? Okay, if not we
 19  will go into closed session, and I'd just ask
 20  the members of the advisory committee to hang
 21  on for just a minute or two, please.
 22              MS. WALSH: It'll just be a

      Page 61
  1  minute. We're just clearing the room. This
  2  is Christine. Okay, Dr. Hetherington, are you
  3  still with us?
  4              DR. HETHERINGTON: I think, yes.
  5  I think the last time I signed off during the
  6  closed session.
  7              MS. WALSH: That's correct, yes.
  8              DR. HETHERINGTON: Okay, well
  9  thanks very much everybody.
 10              MS. WALSH: Okay, thank you so
 11  much Dr. Hetherington.
 12              (Whereupon, the foregoing matter
 13  went off the record at 2:04 p.m.)