Food and Drug Administration

Center for Biologics Evaluation and Research





Meeting # 114:September 25, 2008

Crowne Plaza Hotel, Silver Spring, MD


Committee Members†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††† FDA Participants

Dr. John Modlin, Acting Chair†††††††††††††††††††††††††††††††††††††††††††††† Dr. Norman Baylor

Dr. Seth Hetherington *†††††††††††††††††††††††††††††††††††††††††††† ††††††††††† Dr. Erik Henchal††††††††††††††††††††

Dr. Vicky Debold **††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††† Dr. Carolyn Wilson

Dr. Jose Romero†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††† CDR Timothy Nelle

Dr. Pablo Sanchez†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††† Dr. Keith Peden†††††††††

Dr. Frank DeStefano††††††††††††††††††††††††††††††††††††† †††††††††††††† †††††††††Dr. Jerry Weir††††††††††††


Absent:††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††† †††††††††††

Dr. Lisa Jackson†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††

Dr. Jack Stapleton†††††††††††††††††††††††††††††††††††††††††††††††††††† ††††††††††††

Dr. Peter Gilbert


Temporary Voting Members††††††††††††††

Dr. John Coffin†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††† MedImmune Participants

Dr. James Cook†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††† Dr. George Kemble

Dr. Bruce Gellin†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††

Dr. Stephen Hughes†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††

Dr. Wendy Keitel††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††

Dr. Pamela McInnes††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††

Dr. Steven Self††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††

Dr. Melinda Wharton†††††††††††††††††††††††††††††††††††††††††††††††††††††††††††††



Executive Secretary††††††††††††††††††††††††††††††††††††††††††††††††††† Committee Management Specialist

Christine Walsh, R.N. ††† ††††††††††††††††††††††††††††††††††††††††††††Denise Royster


These summary minutes for the September 25, 2008 Meeting of the Vaccines and Related Biological Products Advisory Committee were approved on _November 5, 2008__.


I certify that I participated in the September 25, 2008 Meeting of the Vaccines and Related Biological Products Advisory Committee and that these minutes accurately reflect what transpired.


______/s/__________________†††††††††††††††††††††††††††††††††††††† _______/s/_________________

Christine Walsh, Executive Secretary†††††††††††††††††††††††††† John Modlin, M.D., Acting Chair


* Industry Representative†††††† ** Consumer Representative††††††††††

The Acting Chair, Dr. John Modlin, called the one hundred and fourteenth Meeting of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) to order at 8:30 a.m. ET on September 25, 2008.†† In Topic 1, the Committee was presented an update on the Office of Vaccine Research and Review (OVRR), Center for Biologics Evaluation and Research (CBER) response to the OVRR Office Site Visit Review Report that was presented to, and approved by VRBPAC committee members on January 25, 2007.In Topic 2, the Committee heard presentations and held discussion on the use of Madin-Darby canine kidney (MDCK) Cells for manufacture of live attenuated Influenza virus vaccines.


An Open Public Hearing was announced.No public comment was offered.


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:



Open Session


Dr. Erik Henchal, FDA opened Topic 1 on February 20, 2008, with the response to the Office of Vaccines Research and Review (OVRR) Site Visit Review Report.Dr. Henchalís overview included a review of comments and recommendations from the Office Site Visit Team, a review of progress towards building a new strategic planning and research management process, and OVRR future plans.Dr. Henchal summarized by stating that the research-regulatory staff support the science-based review and regulation of vaccines and related products; OVRRís unique research program serves to recruit, train, and retain highly qualified scientists; and OVRRís research priorities focus on mandates to assure the safety, purity, potency, and effectiveness of vaccines and related products.Following Dr. Henchalís presentation, CDR Timothy Nelle, Ph.D., FDA, presented an introduction to Topic 2: the use of Madin-Darby canine kidney (MDCK) cells for manufacture of live-attenuated influenza virus vaccines (LAIV).CDR Nelleís presentation included a brief overview of the topic, a summary of advantages of cell-culture production, a list of challenges associated with the use of MDCK cell substrates, and questions to be asked of the Committee.Immediately following CDR Nelle, Dr. George Kemble Ph.D., MedImmune, gave a presentation about the sponsorís manufacturing process.Dr. Kembleís presentation included an overview of the topic, descriptions of the sponsor manufacturing methods used to produce a LAIV in MDCK cells, and risk assessments conducted by the sponsor.The final presenter for the topic was Dr. Keith Peden, Ph.D., FDA, whose presentation included tumorigenicity and oncogenicity issues.


An Open Public Hearing was announced.No public comment was offered.


Following the Open Public Hearing, the questions were presented to the panel for discussion and recommendation.


Based on information presented to the committee regarding whether the preclinical data discussed was adequate to support the initiation of phase 1 clinical studies for LAIV manufactured in MDCK cells, the committee determined:


         By majority vote (10 votes in favor, 3 against, 0 abstained), there were adequate preclinical data to support the initiation of phase 1 clinical studies for LAIV manufactured in MDCK cells.However, the committee also recommended prior to initiating phase 1 studies that the sponsor conduct additional studies to ensure the absence of large DNA fragments in the final product and repeat lysate studies with additional controls.


In discussing additional data that would be recommended prior to moving into larger clinical studies with the product, the committee recommended animal studies with much longer follow-up to observe possible long term effects.


After committee discussion, the meeting was adjourned.