November 18 - 19, 2009
Bethesda Marriott, Bethesda, MD
|Committee Members||FDA Participants|
|Dr. John Modlin, Chair #||Dr. Norman Baylor|
|Dr. Lisa Jackson #||Dr. Lucia Lee|
|Dr. Jack Stapleton ##||Dr. Tina Khoie|
|Dr. Vicky Debold *||Dr. Robert Wise|
|Dr. Jose Romero||Dr. Hector Izurieta|
|Dr. Pablo Sanchez||Dr. Robert Ball|
|Dr. Frank DeStefano||Julienne Vaillancourt|
|Dr. Peter Gilbert #||Dr. Wellington Sun|
|Dr. Margaret Rennels **||Dr. Jerry Weir|
|Dr. Rakesh Pandey|
|Dr. Cynthia Noletti|
|Temporary Voting and Non Voting Members||Speakers|
|Dr. Victor DeGruttola +||Dr. Claudia Vellozzi, CDC +|
|Dr. Bruce Gellin||Dr. Emilio Emini, Wyeth +|
|Dr. Patricia Ferrieri +||Dr. William Gruber, Wyeth +|
|Dr. Pamela McInnes||Dr. Daniel Scott, Wyeth +|
|Dr. Melinda Wharton||LTC. Patrick Garman, Army +|
|Dr. Robert Munford +||Dr. John Treanor, Rochester|
|Dr. Theodore Eickhoff ++|
Dr. Manon Cox, Protein Sciences
Dr. Thomas Fleming ++
|Dr. Roland Levandowski ++|
|Designated Federal Official||Committee Management Specialist|
|Christine Walsh, R.N.||Denise Royster|
These summary minutes for the November 18 - 19, 2009 Meeting of the Vaccines and Related Biological products Advisory Committee were approved on June 24, 2010.
I certify that I participated in the November 18 - 19, 2009 Meeting of the Vaccines and Related Biological Products Advisory Committee and that these minutes accurately reflect what transpired.
|Christine Walsh, R.N.||Jack Stapleton, M.D.|
|Designated Federal Official||Acting Chair|
* Consumer Representative
** Industry Representative
+ Attended November 18 only
# Did Not Attend
## Acting Chair
++ Attended November 19 only
The Acting Chair, Dr. Jack Stapleton, called the Meeting of the Vaccines and Related Biological Products Advisory Committee to order at 8:05 a.m. ET on November 18, 2009. The committee discussed the safety and effectiveness of pneumococcal 13-valent conjugate (Diphtheria CRM197 Protein), was provided an update on FDA’s Influenza A (H1N1) 2009 monovalent vaccine activities, and discussed the safety and effectiveness of influenza vaccine, purified recombinant influenza Hemagglutinin.
An Open Public Hearing was announced for topic 1 and 3. Several public comments were made.
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 2009 Meeting Materials, Vaccines and Related Biological Products Advisory Committee page.
Proceedings were adjourned at approximately 3:00 p.m. ET on November 19, 2009.
On November 18, 2009, after opening administrative remarks, the committee discussed and made recommendations on the safety and effectiveness of Prevnar 13, a pneumococcal 13-valent conjugate vaccine (diphtheria CRM 197 protein), manufactured by Wyeth Pharmaceuticals. The following questions were presented to the committee:
- Are the available data adequate to support the effectiveness of Prevnar 13 when administered to infants and toddlers at 2, 4, 6, and 12-15 months of age, for the prevention of invasive pneumococcal disease caused by serotypes in the vaccine?
- Are the available data adequate to support the safety of Prevnar 13 when administered to infants and toddlers at 2, 4, 6, and 12-15 months of age?
- Please comment on the proposed phase 4 observational safety study.
- Please discuss whether the available data support the effectiveness of Prevnar 13 for the prevention of otitis media.
- Please comment on the proposed post marketing IPD effectiveness studies.
The committee was asked to vote on questions 1 and 2. The other questions were intended for discussion only. The votes for both questions 1 and 2 were 10 yes, 1 no, and 0 abstain. In addition, in response to question 1, individual members commented on how the OPA data were compelling for all serotypes and that there was an impressive OPA response for serotype 3. Comments in response to question 2, pertained to the small size of the phase 3 studies which were conducted to support licensure and the potential long term consequences of hyperimmunization with multiple diphtheria-containing vaccines with a recommendation that arthralgia be included as a pre-specified event in the phase 4 safety study.
Concerning question 3, the applicant was questioned about the length of follow-up for the phase 4 safety study and on issues concerning an ongoing trial in pre-mature infants being conducted in Europe.
In response to question 4, comments were made on the lack of an antibody correlate for protection against OM and the lack of data to support an indication for prevention of OM caused by the six additional serotypes. Most members agreed that the data support an OM indication for the seven Prevnar serotypes, but more data are necessary to support an OM indication for the additional six serotypes and studies in this regard should include tympanocentesis to obtain serotype specific data.
In response to question 5, it was recommended that the existing immunogenicity data be stratified by age groups, one of which should include infants 6-12 months of age. Recommendations to evaluate Prevnar 13 in bone marrow transplant recipients, HIV-infected individuals, splenectomized individuals and solid organ transplant recipients in post marketing studies were also made. The applicant clarified that studies in bone marrow transplant recipients, HIV-infected individuals and individuals with sickle cell disease are ongoing. The applicant also noted that a separate program to evaluate use of Prevnar 13 in adults is underway.
The committee was also provided an update on FDA’s Influenza A (H1N1) 2009 monovalent vaccine activities. Overall, to date, no safety signals of concern in U.S.-licensed H1N1 vaccines nationally or internationally were found.
On November 19, 2009, after a closed session, the meeting was opened to the public and called to order by the Chair. A brief introduction of the topic, safety and effectiveness of influenza vaccine, purified recombinant influenza Hemagglutinin, was made by Dr. Rakesh Pandey of CBER. A brief regulatory history of the development of Flublok and the BLA submission was presented along with some of the review activities related to this application. The committee was also introduced to the questions regarding the safety and efficacy of Flublok to facilitate the discussion after, presentation of the review of the clinical data in support of the application. Dr. Manon Cox presented the safety and efficacy data on behalf of the sponsor, Protein Sciences Corp. (PSC). Her presentation highlighted the advantages of cell derived recombinant influenza vaccine such as shorter production time frame and independence from the need of eggs that could become a rate limiting step. Dr. John Treanor, a collaborator of PSC and also one of their clinical investigators presented the clinical data including the efficacy data from study PSC04 in 18-49 year old healthy adults and talked about the pre-specified exploratory endpoint and 44.6% protective efficacy against any strain using culture positive CDC-ILI endpoint. PSC presentation was followed by Dr. Cynthia Nolletti of CBER. She summarized the detailed review and analysis of the safety and efficacy of Flublok and presented the questions to the committee.
- Is FluBlok effective in:
- 18-49 year olds? Yes-9 Abstain-0 No-2
- 50-64 year olds Yes-5 Abstain-0 No-6
- 65 and older Yes-2 Abstain-0 No-9
- Is FluBlok safe in 18 and older? Yes-5 Abstain-0 No-6
Issues include loss to f/u, re-look at pleuropericarditis, can PCRs be done to establish an alternative etiology?
- Need more safety in ≥65 year olds
- Repeat vaccination and better monitoring for hypersensitivity in all age groups
- Large study of all medically attended Adverse Events and then f/u any signals
- Study special populations: elderly, infants, pregnant women, immunosuppressed populations, autoimmune persons, allergic populations (asthmatics)
- Committee thought that a larger pre-licensure safety study was needed to look for hypersensitivity events because the efficacy benefit is not great
- Consider a post-marketing superiority trial and see if we make mismatch a primary endpoint
- Committee felt that the bar for safety should be higher as this was a novel vaccine and expressed concerns against mass vaccinations with questionable safety
The meeting adjourned at 3:00 p.m.