First Committee Meeting - Cervarix, April 19, 2007

FIRST COMMITTEE MEETING
BLA Number: STN #125259
Sponsor: GlaxoSmithKline Biologicals
Title: “Cervarix® (Human Papillomavirus Vaccine, AS04 Adjuvant-Adsorbed) Intramuscular Injection”
To: Cervarix BLA Review Team
From: Gopa Raychaudhuri, Ph.D.
Chairperson, BLA Review Committee
Subject: First Committee Meeting
Date: Thursday, April 19, 2007
Signature:
FIRST COMMITTEE MEETING – GENERAL PLANNING
Review Team:


Gopa Raychaudhuri
Helen Gemignani
Nancy Miller
Robin Levis Product,
Martha Lee
Lev Sirota
Steve Kunder
Liz Sutkkowski
Marion Gruber
Rebecca Olin
Manette Niu
Solomon Yimam
Lisa Stockbridge
Vada Perkins
Chairperson, Product
Regulatory Co-Coordinator
Clinical
Facility, Pre-clinical immunogenicity
Statistics (clinical)
Statistics (assay validation)
Pre-clinical toxicology (standard tox studies)
Pre-clinical toxicology (adjuvant tox studies)
Pre-clinical toxicology (reprotox studies)
Facility inspection
Epidemiology
Bioresearch monitoring
Promotional labeling
EDR 

Milestones:
  

Application Received:
March 29, 2007 

Committee Assignment:
April 12, 2007 (completed March 30, 2007) 

First Committee Meeting:
April 19, 2007 (conducted via e-mail on April 19, 2007) 

Filing Meeting:
May 13, 2007 (effectively due May 11, 2007) 

Filing Action:
May 28, 2007 

Deficiencies Identified:
June 11, 2007 

Action Due Date:
January 27, 2008 (effectively due Jan. 25, 2007) 

Explanation of Milestones:
  

Committee Assignment:
Date by which reviewers must be assigned to the file. This information must be entered into RMS-BLA. [DONE] 

First Committee Meeting:
Committee must meet by this date to discuss the BLA.
[This memo will be considered to be our committee meeting.] 

Filing Meeting:
Meeting at which the review committee determines whether or not the BLA can be filed. Reviewers must determine whether the information included in the BLA is sufficient to allow the reviewer to conduct an adequate review. The purpose is not to determine the acceptability of the data but rather to determine whether the appropriate information was submitted to allow the reviewer to conduct a meaningful review. 

Filing Action:
Date by which a filing letter (either accepting or refusing to file the BLA) must be issued. The Priority Review request will also be addressed (accepted or denied) in this letter. 

Deficiencies Identified:
Date by which a letter must be issued in which review issues identified to date are conveyed to the sponsor. 

Action Due Date:
 Date by which final action regarding the BLA must be conveyed to the sponsor (issue Approval or Complete
Response letter, depending on review decision). 


Review Timetable:

The timetable given below assumes a standard 10-month review clock for the BLA. The dates listed are “target dates” for completion of specific review-related activities. The purpose is to help with time management, and to ensure that review objectives are achieved in a timely manner. 


Tentative Review Timetable:
    

First Committee Meeting: 
April 19, 2007  (conducted via e-mail on April 19, 2007) 



Meeting to discuss 

 
 May 1, 2007 *** (to determine whether the BLA should be a
priority review issue: standard or priority review) 

Completion of general
overview of information
in your review discipline: 
May 7, 2007 (prep for Filing Meeting) 

Filing meeting by:
May 11, 2007 (may be conducted via e-mail) 

Filing letter by:
May 28, 2007   

Communicate review
issues to be included in
Deficiencies Identified letter:
May 28, 2007 (prep for DI letter which is due on June 11, 2007) 

Deficiencies Identified
letter by:
June 11, 2007   

First draft review memo
(initial assessment):
July 16-29, 2007   

Mid-cycle review meeting:
July 24, 2007 ***   

Detailed evaluation of material
in your review discipline
should be completed:
September, 2007   

Start drafting VRBPAC
Briefing Document:
September, 2007   

Start discussion re:
PMCs October, 2007   


VRBPAC Briefing

Document due: 
 October, 2007   

VRBPAC meeting:
November, 2007   

Start label review:
November, 2007   

Submit detailed draft
review memo:
mid-November, 2007   

Conduct Proprietary
Name review:
mid-end Dec., 2007   

Initiate Compliance check:
mid-end Dec., 2007   

Finalize Lot Release:  
Dec., 2007   

Submit final review memo:
by Jan. 8, 2008   

Finalize approval package:
by Jan. 11, 2008 (at least two weeks before ADD)   

Supervisory review
of approval package:
Jan. 11 (or earlier) – Jan. 24, 2008   

Action Due Date
(issue Approval or CR letter):
effectively Jan. 25, 2008   

 
    


Please note:
•Milestones are marked in blue.
•Helen has sent out notices for the meetings marked with *** already. If you have received either or both of these meeting notices, please click “Accept” to post the meeting on your Outlook calendar (to block off time slot), if you haven’t done so already.
•Scheduling of the VRBPAC meeting for Nov. 2007 is a guess on my part at this time. The final date will be determined later in the review cycle. Associated target dates may have to be modified once the date of the VRBPAC meeting is settled. 

 

Other review activities for which timelines will need to be determined:
•Facility inspection
•BiMo inspections 
•Lot release (testing to be performed,involvement/role of new DPQ group
•Promotional labeling (including proprietary name review) 

 

Please note that currently, this BLA is on a 10-month clock but GSK has asked for a priority review based on claims pertaining to clinical benefits which they claim are not addressed by GARDASIL (Merck’s HPV vaccine). We have scheduled a meeting on May 1st with the clinical and stats groups (since GSK’s “unmet medical need” claims are all clinical), and OVRR upper management to discuss this issue. I’ll follow up with everyone regarding whether this BLA will be a standard or priority review as soon as a decision is reached.

If you are interested in the further details regarding BLA-related activities (including the role of various committee members, administrative responsibilities etc.), please see http://www.fda.gov/cber/regsopp/8401.htm.
Communications with the sponsor:
We can communicate with the sponsor via several different methods e.g., telecons, Secure e-mails, faxes, and letters. I would encourage the following:
•Requests for information or advice for the sponsor should be communicated via Secure e-mail. It is essentially the same as a fax but with the advantage that the communication is automatically deposited in the EDR (and therefore there is a formal record in the file). Additionally, this will allow all reviewers to have access to the information as it will be in the EDR. As the regulatory co-ordinator, Helen is the “gatekeeper” for the Secure e-mail system for this BLA. As such, all Secure e-mails (both those being sent and those being received) will go through Helen. She will send all outgoing Secure e-mails to GSK, and will forward any Secure e-mails received from GSK to the relevant reviewers.
•It may be appropriate to communicate some requests for information (e.g., something that is relatively simple) to the sponsor via a telecon. Please ensure that all such communications are formally documented (i.e., write up a telecon memo and send it to Helen so that she can include it in the file).
•Formal telecons with the sponsor can be scheduled to address issues for which a direct discussion is helpful. Helen will co-ordinate this if/when it is needed. 
•Letters can also be used to communicate review issues to the sponsor. Although both Secure e-mails and letters provide the necessary documentation for the file, letters are a more formal process than Secure e-mails (must go through more levels of supervisory review and concurrence) and so I typically reserve letters for communication of policy or serious review issues. 
•Faxes can be used also, if necessary. A copy of the fax (with documentation that transmission was successful) should be given to mail instead of fax for the reasons given above.
Supervisory concurrence will be sought, when appropriate, prior to sending communications to the sponsor (e.g., memos with request for information, providing advice etc.) 

Final Thoughts … 
•Please contact Helen and/or me if you need to communicate with the sponsor (i.e., telecon, send a Secure e-mail, send a letter etc.). Exceptions: Facility, BiMo, and promotional labeling reviewers typically communicate withe sponsor on their own.  If you do so, please document all communications for the file. 
•Please “cc” me on significant e-mail communications and meetings. It is helpful for me to have a general overview of the review status and review issues in the various disciplines (allows me to have general overview of the review status and review issues in the various disciplines (allows me to communicate more effectively with Loris, Norman, and the sponsor, when necessary). 

If you have any questions during the course of this BLA review, please do not hesitate to contact me or Helen or Vada (if the issues are electronic).

Contact Information:
Gopa Raychaudhuri     gopa.raychaudhuri@fda.hhs    Direct Line: (301) 827-6007
Helen Gemignani         helen.sullivan@fda.hhs.gov     Direct Line: (301) 827-5120

Vada Perkins              Vada.Perkins@fda.hhs.gov      Direct Line: (301) 827-6020


Sent via e-mail to the Cervarix BLA review team members on April 19, 2007:
Helen Gemignani
Marion Gruber
Steve Kunder
Martha Lee
Robin Levis
Nancy Miller
Manette Miu
Rebecca Olin
Vada Perkins
Lev Sirota
Lisa Stockbridge
Liz Sutkowski
Solomon Yimam 
