Food and Drug Administration

Center for Biologics Evaluation and Research

SUMMARY MINUTES

VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE

Meeting # 111:  May 16-17, 2007

Hilton Hotel, Washington DC North/Gaithersburg, MD

 

Committee Members                                                               FDA Participants

Dr. Ruth Karron, Chair +  +++++                                          Dr. Douglas Pratt ***

Dr. Philip LaRussa                                                                  Dr. Therese Cvetkovich ***

Dr. Bonnie Word +++++                                                        Dr. Melisse Baylor ***

Dr. John Modlin ++                                                                Dr. Sang Ahnn ***

Dr. Lisa Jackson                                                                      Dr. Norman Baylor

Dr. Jack Stapleton                                                                   Dr. Willie Vann ***

Dr. Seth Hetherington **                                                       Dr. Dennis Kopecko ***

Dr. Monica Farley                                                                   Dr. Michael Merchlinsky ****

Dr. Steven Self                                                                       Dr. Steven Rosenthal ****

                                                                                               

Temporary Voting Members                                                   May 16 MedImmune Participants

Dr. Hassan Aziz *                                                                   Dr. Edward Connor

Dr. Pamela McGinnes                                                            

Dr. Bruce Gellin *****                                                           May 17 Acambis Participants

Dr. Melinda Wharton  *****                                                  Dr. David Wonnacott

Dr. Robert Daum ***                                                             Dr. John M. Neff

Dr. Gail Demmler ***                                                            Dr. Thomas P. Monath

Ms. Ruth Hoffman *** +++                                                   Dr. Jason W. Mason

Dr. Carolyn Kercsmar ***                                                      Dr. Michael Watson

Dr. Lawrence Moulton ***                                                   

Dr. Limone Collins ****  *****                                            Guest Speakers

Dr. Barry Massie ****                                                            Dr. Alexander Klimov, CDC ***

Dr. Michael Nelson ****  *****                                            Dr. Gerald Parker, DHHS ****

Dr. Gerald Parker ****  *****                                               LTC Stephen M. Ford ****

COL James Schultz ++++

Dr. John Teerlink ****

 

 

Executive Secretary                                                    Committee Management Specialist

Christine Walsh, R.N.                                                 Denise Royster

 

 

* Acting Consumer Representative                            + Chair May 17 only

** Non-Voting Industry Representative                    ++ Acting Chair May 16

*** Attended May 16 only                                        +++ Patient Representative May 16

**** Attended May 17 only                                      ++++ Patient representative May 17

***** Nonvoting Temporary Member May 17          +++++ Not in attendance Topic 1

 

 

These summary minutes for the May 16, 2007 Meeting of the Vaccines and Related Biological Products Advisory Committee were approved on ________June 29, 2007___________.

 

I certify that I participated in the May 16, 2007 Meeting of the Vaccines and Related Biological Products Advisory Committee and that these minutes accurately reflect what transpired.

 

 

_______/s/___________________                 ___________/s/_________________

Christine Walsh, R.N.                                                 John Modlin, M.D.

Executive Secretary                                                    Acting Chair

 

 

 

These summary minutes for the May 17, 2007 Meeting of the Vaccines and Related Biological Products Advisory Committee were approved on _____October 2, 2007______________.

 

I certify that I participated in the May 17, 2007 Meeting of the Vaccines and Related Biological Products Advisory Committee and that these minutes accurately reflect what transpired.

 

 

______/s/_____________________               _________/s/_____________________

Christine Walsh, R.N.                                                 Ruth Karron, M.D.

Executive Secretary                                                    Chair

 

 

 

The Acting Chair, Dr. John Modlin, called the one hundred and eleventh Meeting of the Vaccines and Related Biological Products Advisory Committee to order at 9:00 a.m. ET on May 16, 2007.   In Topic 1, the meeting addressed the safety and effectiveness of FluMist in a pediatric population less than 59 months of age manufactured by MedImmune.  The committee then heard an update on the influenza strain selection for the 2007 – 2008 influenza season.  In Topic 2, the committee heard an overview of the Laboratory of Bacterial Polysaccharides/Laboratory of Enteric & Sexually Transmitted Diseases, Division of Bacterial Parasitic & Allergenic Products, Office of Vaccines Research and Review, CBER and in closed session discussed the report of the Laboratory Site Visit from November 29, 2006.  On May 17, 2007, in Topic 3, the committee addressed the safety and immunogenicity of a live vaccinia virus smallpox vaccine, percutaneous scarification, ACAM2000 manufactured by Acambis, Inc.

 

An Open Public Hearing was announced for each of the Topics.  Public comment was offered during Topics 1 and 3. 

 

 

Following is a summary of the discussion.  Additional information and specific details may be obtained from the transcript of the meeting.  The transcript may be viewed on the World Wide Web at:  http://www.fda.gov/ohrms/dockets/ac/cber07.html#VaccinesandRelatedBiological.

 

 

Open Session

 

Dr. Douglas Pratt, FDA opened the morning session on May 16, 2007, the safety and effectiveness of FluMist in a pediatric population less than 59 months of age manufactured by MedImmune, presenting an introduction and a background overview on the topic.  In his presentation, Dr. Pratt also introduced the questions that would be presented to the committee later in the session.  Following Dr. Pratt, Dr. Edward Connor presented for MedImmune.  Dr. Connor’s presentation included an introduction and overview, data on safety and efficacy of FluMist in children less than 5 years of age, post marketing studies, and overall conclusions on safety and efficacy. Subsequent presentations were made by Dr. Therese Cvetkovich, Dr. Melisse Baylor, and Dr. Sang Ahnn, FDA, and included safety and efficacy data, along with a statistical discussion on safety. Following the FDA presentations, an Open Public Hearing was offered.  Public comments were made by members of the audience.   Following the Open Public Hearing, the questions were presented to the panel for discussion and recommendation.

 

Based on information presented to the committee regarding the efficacy of FluMist for prevention of influenza illness in the following: a.) in the applicant’s proposed population, i.e. children age 12-59 months without history of wheeze, b.) children in the age strata 6-23 months, c.) children in the age strata 24-59 months, the committee recommended:

 

  • The committee unanimously recommended (15 votes in favor, 0 against, 0 abstained) that the data were sufficient to support the efficacy in the applicant’s proposed population, i.e. children age 12-59 months without history of wheeze.
  • The committee recommended in a majority vote (14 votes in favor, 1 against, 0 abstained) that the data were sufficient to support the efficacy in children in the age strata 6-23 months.
  • The committee unanimously recommended (15 votes in favor, 0 against, 0 abstained) that the data were sufficient to support the efficacy in children in the age strata 24-59 months.

 

Based on information presented to the committee regarding whether the safety data demonstrates that the benefits will exceed the risk of FluMist for use in a.) the applicant’s proposed population, i.e. children age 12-59 months without history of wheeze, b.) children in the age strata 6-23 months, regardless of wheezing history, c.) children in age strata 24-59 months, regardless of wheezing history.

 

  • The committee recommended in a majority vote (9 votes in favor, 6 against, 0 abstained) that the safety data demonstrates that the benefits will exceed the risk in children 12-59 months, regardless of wheezing history.
  • The committee did not recommend in a majority vote (3 votes in favor, 12 against, 0 abstained) that the safety data demonstrates that the benefits will exceed the risk in children in the age strata 6-23 months, regardless of wheezing history.
  • The committee unanimously recommended (15 votes in favor, 0 against, 0 abstained) that the data demonstrates that the benefits will exceed the risk in children in the age strata 24-59 months, regardless of wheezing history.

 

The committee then held discussion regarding what additional post-marketing studies or surveillance activities would be recommended if the vaccine is approved for children less than 5 years of age.  Comments and discussion included looking at etiology and getting a better understanding of underlying pathogenesis, following up on children who need to be hospitalized and who would be at significant risk, and a possible focused study on children 6-23 months of age.

 

After lunch, Dr. Alexander Klimov, CDC, presented the committee and update from the February 28, 2007 Vaccines and Related Biological Products Advisory Committee meeting on the influenza strain selection for the 2007 – 2008 influenza season.  Dr. Klimov stated that in overall conclusion, the results are consistent with the February decision to recommend the A/Wisconsin/67/2005 viruses be in the influenza vaccine for the 2007 – 2008 influenza season.

 

The committee then heard presentations from Dr. Willie Vann and Dr. Dennis Kopecko, FDA, regarding overviews of the Laboratory of Bacterial Polysaccharides and the Laboratory of Enteric & Sexually Transmitted Diseases, Division of Bacterial Parasitic & Allergenic Products, CBER.  Following presentations, the committee went into closed session to discuss the report of the June 29, 2006 Laboratory Site Visit.

 

The meeting was then adjourned for the day.

 

The Chair, Dr. Ruth Karron, called day two of the meeting to order at 9:05 a.m. ET.  Dr. Michael Merchlinsky, FDA, opened the meeting with an introduction and background to the day’s topic; safety and immunogenicity of a live vaccinia virus smallpox vaccine, percutaneous scarification, ACAM2000, manufactured by Acambis, Inc.  In his presentation, Dr. Merchlinsky also introduced the questions that would be presented to the committee later in the session.  Following Dr. Merchlinsky, Dr. Gerald Parker, DHHS, presented an overview for the committee on DHHS’s Smallpox Program that included requirements for smallpox vaccination, utilization policy, public health responses, and training and education programs.  LTC Stephen Ford then represented DOD and presented information regarding the Department of Defense smallpox vaccination program.  Following DOD, the sponsor, Acambis, Inc. made presentation to the committee.  The sponsor’s presentation included introduction, history of smallpox, ACAM200 development program, detection and incidence of myocarditis, and a risk management plan. Subsequent presentation was made by Dr. Steven Rosenthal and Dr. Michael Merchlinsky, FDA and included clinical and statistical data, safety monitoring and results, pharmacovigilance goals and concerns, and a re-introduction of the questions to the panel.  Following the FDA presentation, an Open Public Hearing was offered.  Public comments were made by members of the audience.   Following the Open Public Hearing, the questions were presented to the panel for discussion and recommendation.

 

Based on information presented to the committee regarding the safety and immunogenicity of a live vaccinia virus smallpox vaccine, percutaneous scarification, ACAM2000, manufactured by Acambis, Inc., the committee recommended:

 

  • The committee unanimously recommended (11 votes in favor, 0 against, 0 abstained) that the data are sufficient to support the efficacy of the use of ACAM2000 in situations where it is determined that there is high risk of exposure to smallpox vaccine.
  • The committee unanimously recommended (11 votes in favor, 0 against, 0 abstained) that the data are sufficient to support the safety of the use of ACAM2000 in situations where it is determined that there is high risk of exposure to smallpox vaccine.
  • The committee recommended in a majority vote (10 votes in favor, 1 against, 0 abstained) that a Risk Minimization Action Plan (RiskMAP) is needed for ACAM2000 composed of a.) vaccine education, b.) health care provider education, c.) expedited reporting of certain adverse events, d.) Phase 4 studies to better define the safety profile, long term outcomes, and risk factors for myocarditis, and e.) evaluation of the RiskMAP.

 

The panel then moved to the discussion portion of the questions and agreed that they can discuss the risks, however, have no way of knowing information about the potential benefits of the vaccine relative to credible risk information.  Comment was also made that safety considerations need to be taken very seriously.  Other comments and recommendations included the need to have electrocardiograms and troponins, the need for an echocardiogram sub-study of echocardiograms at baseline with serial study follow-up, and for those who develop myocarditis, a formal mechanism of referral for follow-up care once people leave the military.  Additionally, to increase sensitivity of case ascertainment, the use of methods other than reporting of symptoms is needed.

 

The Chair adjourned the meeting at 3:15 p.m. ET.