DATE: November 15, 2007
FROM: Laraine S. Henchal, Microbiologist Reviewer, DVRPA, CBER, Review Committee Chair, STN 125265/0
SUBJECT: BLA STN#125265/0, Rotarix®, Mid Cycle Review Meeting
The committee met on November 15, 2007 to discuss status of review of BLA/STN #125265/0 for Rotarix® Rotavirus Vaccine Live Oral from GlaxoSmithKline Biologicals.
Hector Izurieta addressed the Risk Management Plan. There were several cases of Kawasaki's disease identified. Further info is being sought on this and will need to be addressed in post-marketing study. Other possible signals noticed were convulsions, and pneumonia deaths; both will need to be addressed further in post-marketing study. We will recommend that he U.S. post-licensure study be at least as large as that of Merck for Rotateq®.
Paul Kitsutani addressed the clinical studies. An analysis of the safety data including studies 023, 036, 040 and 060 have shown no additional signals other than those mentioned by Dr. Izurieta. Heis working with Dr. Kou to confirm the efficacy/immunogenicity numbers as analyzed from the datasets. The data as presented appear to support the concomitant adminstration (study 060) of other vaccines currently licensed in the U.S.
Dr. Jingyee Kou will have a few items to forward to the company in regards to the statistical analysis of the clinical data. She will forward those so that they may be incorporated into an information request. Dr. Kitsutani also has a number of items for which clarification is needed.
CMC-Dino Feigelstock identified some issues which will be examined during the inspection now scheduled for the first two weeks in December. Examples include -- ----- ----- specification for potency, correlation between the ffu and CCID50 assays, testing for attenuation of the vaccine virus, etc.
Other participants updated the group on their area of expertise. The BiMo inspections have been assigned and some have been conducted. Expected to complete in Jan 08. Proprietary name review will need to be completed within 90 days of action due date. The name was accepted while under the IND, and no changes have been made since then. Assay validation reviews are proceeding. A number of items will need further clarification from the manufacturer.
Participants were urged to complete their initial reviews and identify issues which need to be conveyed to GSK. The aim will be to get the information request together before the holidays. Send comments to either Luba Vujcic or Laraine Henchal.
The Advisory Committee meeting is likely to be held on February 20 or 21, 2008. Testing plan is being developed. DPQ is not sure that CBER will be testing this product or not yet. It is time to work on the Lot Release Protocol and figure out samples that will need to be submitted for testing of lots in support of licensure. A new FDAAA requirement will necessitate a presentation before a committee to advise on PREA waiver/deferral for this vaccine at some point previous to action due date.
CBER committee members present at meeting:
M. David Green
Robin Levis (attendee)