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Vaccines, Blood & Biologics

Record of Telephone Conversation, September 7, 2012 pm - Flucelvax


Submission Type: BLA    Submission ID: 125408/0    Office: OVRR
Influenza Vaccine (MDCK Cells)
Novartis Vaccines and Diagnostics, Inc.
Telecon Date/Time: 07-Sep-2012 03:14 PM        Initiated by FDA? Yes
Telephone Number: Communicated via e-mail
Communication Categorie(s):
1. Advice
2. Information Request
Telecon Summary:
Residual virus, SRID, lot release protocol.
FDA Participants: Timothy Fritz
Non-FDA Participants: Matthew Gollwitzer
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
Telecon Body:
From:                    Fritz, Timothy
Sent:                      Friday, September 07, 2012 3:14 PM
To:                         'Gollwitzer, Matthew'
Subject:                 CBER Information Request STN 125408 (Flucelvax)
Importance:           High
Dear Mr. Gollwitzer-
Our review of Novartis' submission STN 125408 (Flucelvax) is ongoing. We have the following requests for additional information:
1. Please include the SOP numbers in the LRP in the "Tests on Control Cells” box which are under Section 2.1.1, 2.2.1 and 2.3.1, "Control Cells for Monovalent Bulk Lot".
2. Please clarify at which stage the "Absence of extraneous viruses" testing will be performed------        --------------------(b)(4)------------------------------------------------. If these tests will be performed after the --------(b)(4)----------------, please comment on whether these processes would affect the test results.
3. Please provide a qualification report to show that A/Victoria/361 egg-based reagents are suitable for the SRID testing of MDCK cell grown vaccine.
4. Because a cell-based reference antigen for B/Wisconsin is available from NIBSC, CBER recommends using this reference for SRID testing. Please comment.
5. The information provided by Novartis via e-mail on September 5, 2012 for CBER comment 11a did not include the residual infectious virus validation documents with virus lots and titers as requested in the August 24, 2012 telecon between CBER and Novartis. Please provide this information.
6. In the information provided by Novartis via e-mail on September 5, 2012 for CBER comment 11b, Novartis did not discuss the 2 options agreed upon by CBER and Novartis in an August 24, 2012 telecon. Please comment on the options described below.
Option 1:
If Novartis is unable to provide validation data demonstrating that the test for residual infectious virus performed in ---(b)(4)--- is at least as sensitive as the test performed in              -----(b)(4)------------, Novartis should test the first 3 ----(b)(4)----------- lots from each annual influenza season for residual infectious virus in both the --------------(b)(4)------------------------. All 3 lots for all seasonal strains must pass the test in both substrates. Subsequent lots manufactured during the season can be tested by the ---(b)(4)----- method only.
Option 2:
Alternatively, if Novartis can provide validation data demonstrating that the sensitivity of the residual infectious virus test performed in ---(b)(4)------- is at least as great as the test performed in ----(b)(4)--------------, then Novartis may release ---------(b)(4)----------------------------------------------- by the test performed in ---(b)(4)----- only. A possible experiment suggested by CBER to validate the sensitivity of the assay which should be demonstrated for at least 3 strains representing H1N1, H3N2 and B types was as follows:
 ------(b)(4)--------- lots (at least 3 lots for each strain) spiked with serial dilutions of the same strain of MDCK cell grown influenza virus of known concentration ---(b)(4)--------- should show at least similar or higher sensitivity in detecting spiked virus by the ---(b)(4)---- test as compared to the ----(b)(4)-------------- test. As per the theoretical explanation provided by Novartis during the August 24, 2012 telecon that the sensitivity of ---(b)(4)---- is significantly higher than the ----(b)(4)-------------, CBER suggested that Novartis could perform the test at one spike level of ---(b)(4)-------- and show that such a spike cannot be detected by (b)(4), but could be readily detected by ---(b)(4)-----.
Please submit the requested information as an amendment to STN 125408 as soon as possible. We recommend that you restate each item and follow it with your explanation or clarification. 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 the Regulatory Project Manager, Drs Brenda Baldwin or Timothy Fritz, at 301-796-2640 or via e-mail.
Thank you.
Timothy A. Fritz, Ph.D.
WOC2 HFM-478
1451 Rockville Pike
Rockville, MD 20852
Phone: 301-796-2640
Fax: 301-827-1597
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Page Last Updated: 12/19/2012
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