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Vaccines, Blood & Biologics

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Vaccines

Record of Telephone Conversation, March 13, 2012 - Flucelvax

 

Submission Type: BLA    Submission ID: 125408/0    Office: OVRR
Product:
Influenza Vaccine (MDCK Cells)
Applicant:
Novartis Vaccines and Diagnostics, Inc.
Telecon Date/Time: 13-Mar-2012 04:15 PM        Initiated by FDA? Yes
Telephone Number:
Communication Categorie(s):
1. Information Request
2. Advice
 
Author: BRENDA BALDWIN
Telecon Summary:
Product IR/advice
FDA Participants: Brenda Baldwin, Timothy Fritz
Non-FDA Participants: Matthew Gollwitzer
Trans-BLA Group: No
 
Related STNs: None
Related PMCs: None
E-mail Body:
From:              Baldwin, Brenda 
Sent:                Tuesday, March 13, 2012 4:12 PM
To:                   'Gollwitzer, Matthew'
Cc:                   Fritz, Timothy
Subject:           STN 125408 Optaflu
 
Matt,
 
We have the following comments and requests for information regarding the Optaflu drug substance and drug product:
 
1.      Please provide the procedures that will be used to establish the optimal growth/protein yield conditions, such as multiplicity of infection, (b)(4)-- activity, etc., for each different virus strain used during the initial characterization or screening.
 
2.   Please provide the procedures that will be used to establish the optimal splitting conditions of CTAB for each new strain.
 
3.   Please clarify whether the (b)(4) testing for the absence of extraneous viruses performed at the ---(b)(4)----- stage after ------(b)(4)------------------------ is performed on the first three batches of each new strain or on every production batch. Please confirm that the viruses targeted for testing by (b)(4) at this stage are restricted to ------(b)(4)-------------,                                             ---------------(b)(4)-------------------------------------.
 
4.   Please provide the validation report for the host cell protein (b)(4) (Report 403410).
 
5.   Please include ---(b)(4)----and endotoxin in the release testing of the ----(b)(4)--------------.
 
6.   Please include residual infectious influenza virus in the release testing of the ---(b)(4)---.
 
7.   Please provide the updated stability data (real-time and accelerated) for the monovalent bulk and the final container (syringe without needle, PRTC). The stability data of HA antigen in the final container determined by SRID assay in this BLA complies with the (b)(4) requirements, which is ---(b)(4)------.  Please note that all future stability studies should follow CBER SRID specification for the finished product of not less than ---(b)(4)----.
 
8.   Regarding the validation of BPL inactivation, please provide the technical reports associated with Figure 3.2.S.3.2.6-2, Figure 3.2.S.3.2.6-3, Table 3.2.S.3.2.6-1, and Table 3.2.S.3.2.6-2 (from 3.2.S.3.2 Impurities).
 
9.   Please clarify that the column regeneration procedures for the (b)(4) column is the same as that for the (b)(4) column.
 
10. The --------------------(b)(4)----------------------------- are proposed to be used for up to (b)(4) production runs and are shared between different influenza virus strains. Please provide the procedures that will be used to prevent carryover contaminants (e.g., cell-derived impurities, process residuals, etc.) from one strain to another.
 
11. ------(b)(4)-------------- is used for the (b)(4) column regeneration instead of ---(b)(4)-----. Please provide data to support (b)(4) column performance and stability after storage under -----(b)(4)-------------- with your proposed hold time. Please also provide data to demonstrate that the column regeneration with -----(b)(4)--------------- is sufficient to effectively remove viruses from the column matrix (using the worst case scenario). In addition, please provide data to show that the lifetime of the column (new and used resin) has no impact on virus removal during column regeneration procedures.
 
12. Please provide the following documents related to the assessment of risk associated with             residual DNA: (1) DRA-Application of Defined Risk Assessment to Use of Cell Bank, (2)             Chiron pre-read 5-4188B1_18, (3) Report 228847, (4) Report 235243, (5) Report 229373,             (6) Report 250384, and (7) Report 280908.
 
In your official response to this memo, we recommend that you restate our request and follow it with your response. Use of this format helps organize the relevant information and provides a self-contained document that facilitates future reference. If you have any questions, please contact Dr. Brenda Baldwin and Dr. Timothy Fritz.
 
Regards,
Brenda