|Proper Name:||Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant|
|Meeting Date:||June 17, 2009|
|Time:||10:30am – 12:30pm|
|BLA Review Team:|
|Robin Levis||Chair, Product, Facility, Pre-Clinical|
|Helen Gemignani||Regulatory Project Manager|
|Laura Montague||PERC and VRBPAC RPM|
|Deanna Shone||Electronic Integrity|
|Lev Sirota||Assay Validation Statistics|
|Marion Gruber||Developmental Toxicology|
|Liz Sutkowski||Adjuvant Toxicity, CMC for MPL|
|Steve Kunder||Pharmacological Toxicology|
|Rebecca Olin||Facility CMC, Inspector|
|Gang Wang||Facility CMC, Inspector|
|Solomon Yimam||Bioresearch Monitoring|
|Lisa Stockbridge||Promotional Labeling|
|Gennady Rezapkin||Potency assay|
Helen Gemignani, Nancy Miller, Deanna Shone, Loris McVittie, Andrea Sutherland,
Jeff Roberts, Martha Lee, Elizabeth Sutkowski, Laura Montague, Robin Levis, Rakesh Pandey, Rose Tiernan, Wellington Sun, Maureen Hess, Lev Sirota, Ruby Lerner, Michael Nguyen, Marion Gruber, Rajesh Gupta, Lisa Stockbridge, Rebecca Olin
|Resubmission Review Cycle Timetable:|
|April MonthlyTeam Meeting||April 24|
|VRBPAC Planning Meeting||May 15|
|Internal PREA Decision||May 27|
|Mid-cycle Review Meeting||June 17|
|Draft Review Memos Due||June 28|
|Proprietary Name Review||July 1|
|PeRC Presentation||July 8|
|First Labeling Meeting||July 17|
|VRBPAC Briefing Docs Due To CBER Management||July 24|
|Final Reviews Due||July 28|
|Determination of PMCs/PMRs||August 11|
|Notify FDAAA SWG of PMRs||August 11|
|RPM begin draft of Action Letter||August 25|
|1st VRBPAC Run-Through||August 25|
|Action Pkg to Management||September 1|
|2nd VRBPAC Run-Through||September 1|
|Action Due||September 29|
|CBER Correspondence with GSK Since Resubmission:|
|Clinical (PREA)||April 1|
|eIntegrity Issues||May 15, 22, 28|
|VRBPAC items||May 18, 20|
|Amendments Submitted to the BLA Since Resubmission:|
|0049||eIntegrity - Replacement of Corrupt Datasets (Response to IR)|
|0050||PREA revised (Response to IR)|
|0051||Draft VRBPAC Briefing Document; Epidemiology (Response to IR)|
|0052||eIntegrity (Response to IR)|
Mid-Cycle Review Summary:
Ms. Gemignaniprovided some regulatory advice and reminders to the team as well as status updates:
Review Memos Notes: Please note some important information requested to be included in your Review Memo(s):
- On the first page, please list:
- the sections of the BLA reviewed
- each Amendment number reviewed
- Any Information Requests you asked for from GSK
- which Amendment responded to your request, and
- whether their response was acceptable
The review team was reminded that their draft review memos are due by June 28, 2009, and their final review memos are due July 28, 2009.
VRBPAC planning is on track. Panel experts are being contacted and invited to join the September VRBPAC.
Cervarix is scheduled on the PERC committee agenda for July 8. Dr. Jeff Roberts will prepare the documentation for and present to the PERC.
Deanna Shoneprovided an update that corrupted files were identified in the BLA resubmission, by CBER, and they were replaced by GSK. BLA communications in EDR have been QCed for proper certification and will continue to be QCed until after Action Due.
Dr. Levis is working to complete her draft review by the end of the month. Bulk and final product specifications for CMC are acceptable. She has been working with Dr. Rezapkinon his potency testing and his summary memo indicates that ----b(4)------------------------- assay is coincident with GSK’s results. In addition, she and Rebecca Olin will be conducting an inspection of the MPL manufacturing site from June 22 - 26. She will complete her inspection report and follow up on any findings on the inspection upon returning. Both site inspection report documentation needs to be completed. Dr. Levis does not have any additional issues related to the product review and will be able to finalize her review memo, including the inspection report by the end of July. The Chair SBRA Memo will be drafted for the Action Package by September 1 and finalized after VRBPAC prior to Action Due.
Dr. Miller is preparing VRBPAC slides and her presentation, her clinical review memo and labeling review.
Dr. Lee expressed concern in her review for imbalances in spontaneous abortions. NCI pooled data from studies HPV-008 and HPV-009 and it can not be excluded that there may be a relationship between spontaneous abortion and use of Cervarix. Dr. Gruber inquired as to the background rates of spontaneous abortion in other countries. Dr. Lee responded that it is very wide range and very difficult to determine discrepancies.
Dr. Sutherland provided an update on GSK’s Phase IV study that was scheduled to be conducted in Scotland. GSK has informed FDA that the Scotland study is no longer feasible to conduct and they can not pursue. GSK wants to do a study in the US and are in the planning and design stages now. They will submit a concept protocol to the BLA in July. International PSURs are not robust and there is very little safety data pre-licensure for this adjuvant. It was discussed whether this concept protocol would be a Major Amendment. Dr. Sutherland said that she can work with GSK until September 29, without designating the submission as a Major Amendment. Dr. Gruber questioned whether we should consider a Post Marketing Requirement (PMR) for the pregnancy registry. This will be discussed internally at a meeting to be set up as soon as possible.
The Testing Plan was discussed and it was agreed that a meeting should be set up with the Product Release Branch, DPQ, and Dr. Levis to review the lot release protocols.
Dr. Sirota had no issues with his review and none to share at this meeting.
Dr. Sutkowski has reviewed her CR response items and they are acceptable.
Dr. Gruber has completed her final review memo and will submit. One CR response item for reproductive toxicity was merged with clinical items, in the CR letter, and she has deferred response to that item to Dr. Miller for review.
Dr. Stockbridge will begin review of the Proprietary Name on July 1 in accordance with FDAAA timelines. She does not foresee any issues and will provide labeling comments for the July 17 labeling meeting. Her final evaluation will be forthcoming.
Laura Montague reported that an adjuvant expert is still needed for the VRBPAC. Discussion ensued of various adjuvant experts that the agency would like to engage.
Maureen Hess reminded Ms. Gemignani that she will need a copy of the draft label for press release preparation and to please cc her on labeling issues and meetings.