Mid-Cycle Meeting Summary - VARIZIG, October 1, 2012

Date: October 1, 2012
From: Nannette Cagungun CBER/OBRR/DBA, HFM-380
To: 125430/0
Subject: Mid-cycle review of the Varicella Zoster Immune Globulin (Human) BLA



CBER Participants: 
Alpita Popat
Nannette Cagungun
Howard Chazin
Douglas Frazier
Basil Golding
Anthony Hawkins
Nisha Jain
Michael Kennedy
Erin McDowell
Iftekhar Mahmood
Charles Maplethorpe
David Menschik
Dorothy Scott
Evi Struble
Chiang Syin
Maria Luisa Virata-Theimer
Michael Vardon
Pei Zhang

Discussion:
Pei Zhang informed the review committee that the CMC reviewers discussed the lot release testing plan with DBSQC and that Karen Campbell of DBSQC agreed to draft the testing plan.

Maria Virata-Theimer was able to contact Philip Krause of OVRR to get him to review the potency assay as a consult reviewer.

Alpita Popat reviewed the proprietary name and found it acceptable; however, she noted that Cangene uses tallman lettering in their proposed proprietary name. She explained that the Agency determines when to use tallman lettering and reserves it to create a distinction in a proprietary name to reduce medication errors when appropriate. APLB does not recommend the use of tallman lettering in this instance.

Charles Maplethorpe presented his review of the clinical section of the BLA. He raised the following issues:
•----b(4)--------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
•The BLA safety database for study VZ-009 is deomonstrably incomplete.
•Study VZ-009 was not and adequate and well-controlled study.
•Adverse events (including thrombotic/coagulopathic events) were observed in the expanded access, open-label study VZ-009.
•Reviewers should determine if the –b(4)---- to measure potency is validated for clinical relevance (----b(4)---------)

Iftekhar Mahmood said that VARIZIG and VZIG are not bioequivalent. The potency of VZIG is 2.3-fold higher than VARIZIG.

Erin McDowell noted the absence of adverse events (AEs) in one of the clinical trial sites. CBER will check if there is under-reporting of AEs in the remaining clinical sites. It was also noted that Form 1572 was not signed until three weeks after product administration.

Nannette Cagungun will send the information request to Cangene before the end of the week and asked the review committee members to provide their comments by October 3rd.

The meeting ended.
