Record of Telephone Conversation - VARIZIG, December 3, 2012

RECORD OF TELEPHONE CONVERSATION

Submission Type: BLA Submission ID: 125430/0

Product: Varicella Zoster Immune Globulin (Human)

Applicant: Cangene Corporation

Telecon Date/Time: 3-Dec-2012 1:00 PM Initiated by FDA? Yes

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

Communication Categorie(s): Information Request

Author: MARIA L. VIRATA-THEIMER

Telecon Summary: 
To discuss the potency assay used to test Varicella Zoster Immune Globulin (Human)(VZIG), Varizig, including:
1. Details of how the –b(4)---------- is related to the ----b(4)------------------------
2. Details of the potency assay validation, i.e., dilutions, use of the WHO International Standard for VZIG, relation of the WHO international standard to internal control standard

FDA Participants
Dorothy Scott
Philip Krause
Michael Kennedy
Pei Zhang
Maria Luisa Virata-Theimer

 

Non-FDA Participants (Cangene Corporation)
Derek Toth- Director, Bioanalytical and Quality Sciences
Joy Bosica- Manager, Q.C. Analytical (IP, FP, Release testing)
Lori Soluk- Manager, Validation
Steve McGregor – Director, Regulatory Affairs
Terry Kraynyk – Manager, Regulatory Affairs
Shelley Toth- Senior Associate, Regulatory Affairs
Reem Rahil Khazen- Associate, Regulatory Affairs

Telecon Body:

1. Cangene clarified that the ---b(4)------------------------------------------------------------------------ are the same assay and that only the name had been changed. Method validation was done in 1997. The sponsor agreed to provide a letter from –b(4)--------------- attesting to this name change and that no other changes have been made to the –b(4)------ since 1997.

2. The sponsor stated that their dilutions are done using the –b(4)----------- that is part of the b(4)-----. Cangene clarified that although the product potency specification is 125 IU/ml, and the assay linear range is up to –b(4)-, that they –b(4)--the product using the –b(4)---------------, into the linear range. Cangene has added ---b(4)-------- points to the specified –b(4)-- in the --b(4)----------------------------- that are intended to be below and above the linear range, respectively. This is acceptable.

3. FDA stated that it was not clear from Cangene’s current potency test method SOPP (and the other BLA documents provided) whether the sponsor is currently using both the WHO International Standard for VZIG and an in-house standard. The sponsor clarified that they currently use only the WHO International Standard for VZIG in their potency testing and have yet to use an in-house standard for the determination of potency. Because in-house standards run the risk of potency slippage as they are consecutively changed over time (--b(4)---------------------------------------- it would be necessary for FDA to review any such change from the WHO standard to an internal standard following full validation of the new standard and including multiple comparative tests for precision. Cangene stated that they will only use the WHO International Standard. They agreed to revise their test method SOPP accordingly to reflect the current practice of not using an in-house control. They will provide the revised version and indicate where and which changes have been made. In the event that they need to switch to an internal control standard (e.g., in case the WHO International Standard becomes unavailable), Cangene agreed to submit a PAS to FDA. In-house controls may still be used for assay performance monitoring.

Action Items:

1. Cangene will submit a letter from ---b(4)--------- stating that the ----b(4)---------------------------------------------for Varicella antibodies is changed in name only from the –b(4)---------------.   Cangene will confirm to the BLA that no major changes to the assay have been made since their validation studies in 1997.

2.  Cangene will revise the test method SOPP(s) for the potency assay (--b(4)----- final product) to state that only the WHO standard will be used.   The revised SOPP(s) will be submitted to the BLA in track changes as well as the final form.

Cangene confirmed that de facto, only the WHO standard has been used for potency assessment for the final product.  If Cangene wishes to also have an interim standard approved, as a back up if the WHO standard is unavailable, they may submit such a request with data as a PAS, after licensure.
