
3/17/2008 Telecon 2 - Rotarix

 

 
MEMORANDUM

DATE: March 17, 2008

FROM: Laraine S. Henchal, Microbiologist Reviewer, DVRPA, CBER, Review Committee Chair, STN 125265/0

SUBJECT: Second telecon to discuss the the potency release specifications for STN #125265/0, Rotarix®, Rotavirus Vaccine, Live, Oral from GlaxoSmithKline Biologicals 

This meeting was held to discuss GSK's March 7, 2008 response to the previous meeting held on February 29, 2008. The lot release potency specification now proposed by GSK is to release final product at a titer of ---------------------------------------------------------. End-of expiry titer is then stated as --------------------------- Requested dating period is -- months.

We don't consider the response to be satisfactory. It appears from what was submitted that the variability of the potency assay is actually around --- and not ---, which had been cited previously. The maximum titer at release should still not exceed the maximum titer that was studied in the clinical trials, therefore ----- should be the maximum for Iot release (thereby assuring with 95% confidence that the material's potency does not exceed --- given the --- variability). The lower end-of-expiry is harder to deal with due to the lack of data points. Does GSK have additional data on lots for stability? Yes, they do, but thought that they were only able to include stability for the actual lots used for the Phase 3 clinical studies. CBER replied that GSK can use any number of lots prepared with the same manufacturing process that will be licensed. GSK replied that they will have much more additional information to provide us on the stability in that case. CBER emphasized that the stability needs to be evaluated appropriately with statistical analysis of the regression line, slope and the standard error of the slope line. This will give us a better handle on the loss of potency over time. But it may be that the end expiry titer will be in the ----------- range.

GSK agreed to reconsider their specifications and will submit an additional data on the stability and a re-analysis of the data.

CBER participants:

Laraine Henchal
 Steve Rosenthal
 Paul Kitsutani
 Jingyee Kou
 Luba Vujcic
 Phil Krause
 Dino Feigelstock
 Erik Henchal
 Jerry Weir
 Norman Baylor

GSK participants:

Leonard Friedland
 Donna Boyce
 Benedicte Dupasquier
 Norris Pyle
 Serge Debrus
 Corine Lecomte
 Isabelle Pierard
 Jean-Claude Mareschal
 Michael Vanderwerf
 Isabelle Ernest
 Michel Duchene
 David Le-Tallec
 Brigitte Cheuvart
 Remon Abu-Elyazeed
 Barbara Howe
