
Record of Telephone Conversation, IR Comments, May 3, 2012 - MenHibrix
 
 
Submission Type: BLA    Submission ID: 125363/0    Office: OVRR


Product:
 Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine


Applicant:
 GlaxoSmithKline Biologicals


Telecon Date/Time: 03-May-2012 10:00 AM        Initiated by FDA? Yes


Telephone Number: ------(b)(4)--------


Communication Categorie(s):
 1. Information Request

 Author: KIRK PRUTZMAN
 Telecon Summary:
 Tcon to discuss the 5/2/2012 IR sent to GSK 


FDA Participants: KIRK PRUTZMAN, JOSEPH TEMENAK, DAVID STATEN, TINA ROECKLEIN, WILLIE VANN, MICHAEL SCHMITT, JAMES KELLER, RAJESH GUPTA, WILLIAM MCCORMICK, KAREN CAMPBELL, ALFRED DEL-GROSSO


Non-FDA Participants: Nancy Cauwenberghs, Bert De Klerck, Jody Gould, David Le Tallec, Catherine Poty, Norris Pyle, Catherine Vigano-Wolff 

Trans-BLA Group: No

 Related STNs: None


Related PMCs: None


Telecon Body:

CBER and GSK met to discuss the IR comments sent to GSK on 5/2/2012.  At the beginning of the meeting CBER stressed that all IR comments need to be resolved prior to approval.  GSK indicated that they had not had enough time to fully respond to the 5/2/2012 IR and that this meeting.

Item 1a. Please provide a detailed scientific explanation for the 20% difference in results between the two sites.

Discussion:  GSK indicated that the difference was due to different methods being used in the two sites.  CBER indicated that we want a solid, scientific explanation for the difference.

Item 1b.    We do not concur with setting specifications and expiry dating using the justification of the (b)(4) bias based on testing of (b)(4).  Please revise your expiration date to(b)(4) months for Purified TT manufactured at (b)(4--).  Please revise your release specification for Purified TT manufactured at (b)(4--) to not less than(b)(4).

Discussion:  GSK responded that they are generating data and will be able to submit it in the future.  CBER discussed that the current data available only supports a (b)(4) month stability expiration date.  The label will only support (b)(4) month stability until GSK provides conclusive data for (b)(4) month stability.

Item 1c:  Please provide a detailed PMC for alignment of the two methods.  Suggested wording is as follows:

-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
.

Discussion:  GSK will use the PMC in Item 1c.  Changes in exact language will be discussed with CBER in the near future.

Item 2a:  We recognize that the free PS contents are now reported as a limit when the results are less than the LOQ.  The recalculated result for MenC-TT Batch                         ----(b)(4)------- for Free Polysaccharide C Content by(b)(4) at ---(b)(4)---- (Table 8).  The LOQ is (b)(4).  Please explain why this result is reported as (b)(4) and not (b)(4).

Discussion:  GSK indicated that the discrepancy was a typo.

Item 2b:  We note that the results for Free TT Content by (b)(4) and Free (b)(4) by--(b)(4)--- are also reported as limits of varying results.  Please confirm that this is for the same reason in that the result is reported as a limit when the result is less than the first calibration point.  For consistency, if the value is below the LOQ it should be reported as < LOQ value.  Please comment.

Discussion:  GSK agreed to look into the varying results.

Item 3a:  GSK would like to propose the addition of toxicity testing at ---(b)(4)-- instead of -------(b)(4)--------- TT.

We concur with the proposal but would appreciate some additional information.  Please confirm that final (b)(4) is your final formulated (b)(4).  Please provide information on how the specific toxicity testing will be performed on --(b)(4)--.

Discussion:  GSK agreed.  GSK will provide more information in a written answer.

Item 3b:  GSK will continue toxicity testing on -------(b)(4)---------------o.

Discussion:  GSK agreed with this proposal.

Item 3c:  GSK would like to remove (b)(4) testing on final container.

We do not concur with this proposal.  An exemption from the (b)(4)  will require demonstrating that multiple lots of product will reliably pass the test.  There is not enough safety data to approve an exemption from (b)(4) at this time.  Please submit a prior approval supplement containing (b)(4)  data from (b)(4)  Lots to request an exemption from future testing.

Discussion:  GSK agreed with this proposal.

Item 4a:  You state that PS Content stability testing (Hib, PSC, and PSY) is performed by             ----------(b)(4)-------------.  Please confirm that any final container testing (release or stability) is performed by----------(b)(4)-------------.  .

Discussion:  CBER indicated that the stability testing should be done in conditions similar to marketing conditions.  In this case, reconstitution should be done using the saline diluent.  GSK understood but was concerned that they had limited data and the new specifications using saline might be necessary.  CBER indicated that GSK could use the specifications determined using (b)(4) as temporary specifications and could submit a new set of specifications as a supplement after approval.  

Item 4b:  You state that specifications of PS content have been set based on reconstitution in (b)(4) .  You are currently evaluating if the specifications are appropriate for reconstitution in saline.  Please explain why you anticipate the specification to change for the different reconstitution methods. 

Discussion:  GSK indicated that they were not sure if there was a difference but were concerned that using saline diluent would require re-validation of the assays.  CBER indicated in this tcon that they would get back to GSK regarding any necessary re-validation required for reconstituting in saline.  In a follow-up tcon with GSK, CBER indicated that re-validation would not be necessary and any new specifications the result from using saline could be submitted as a Prior Approval Supplement.  

Item 5:  You provided the following PMC in your response dated 15 April 2011.

----------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------.

Revised wording of the PMC is suggested below.  Please provide a date when you anticipate being able to submit the review of specification.

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Discussion:  GSK agreed to PMC and will get back to CBER about timing.

Other general discussion:

CBER stressed that we have not yet received the reagents for PS testing.  GSK indicated that they were planning on sending the reagents in the next couple of weeks.  CBER stressed that they should be sent earlier.

CBER asked how GSK was assigning lot numbers to the outer carton box.  GSK was not sure but indicated it would be a unique lot number and the expiry date would correspond to the earliest expiry between the lyophilized vaccine and the diluent.  CBER also stressed that the lot number and expiry should be printed on the outer carton labeling and that using stickers to label the lot number and expiry would not be acceptable.  GSK understood.

CBER asked GSK when they planned to submit updated language for their PMC to study the concomitant administration of MenHibrix with Rotorix and Havrix.  GSK indicated that final language was being approved and it should be sent to CBER shortly.  
