Record of Telephone Conversation, June 22, 2012 am - Flucelvax
Submission Type: BLA Submission ID: 125408/0 Office: OVRR
Influenza Vaccine (MDCK Cells)
Novartis Vaccines and Diagnostics, Inc.
Telecon Date/Time: 22-Jun-2012 09:00 AM Initiated by FDA? Yes
Telephone Number: Communicated via e-mail
1. Information Request
Author: TIMOTHY FRITZ
Columns, RBCs, facilities
FDA Participants: Timothy Fritz
Non-FDA Participants: Matthew Gollwitzer
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
From: Fritz, Timothy
Sent: Friday, June 22, 2012 9:01 AM
To: 'Gollwitzer, Matthew'
Subject: CBER Information Request for STN 125408
Attachments: CBER 22 June 2012 Information Request STN 125408.doc
Dear Mr. Gollwitzer-
Our review of Novartis’ BLA submission STN 125408 is ongoing. We have the following requests for additional information:
1. We acknowledge that you have a procedure for regenerating the -------(b)(4)------ columns between product loads for each production run and between influenza strain changes. However, data have not been provided to assure that no crossover strain contamination occurs, especially between manufacturing campaigns when there is a strain change involved. Please provide data and specify what tests have been implemented to address this concern.
2. In order to directly compare Process 1.0 and Process 1.1, please provide the ---(b)(4)---------------------of three monovalent bulk lots for the same influenza virus strains manufactured using these two processes.
3. Please clarify whether ----(b)(4)---red blood cells (RBC) will be used as an alternative or replacement to --(b)(4)--RBC in future measurements of hemagglutinin (HA) titers. In the validation report for this test, you only provided data for H1 testing using ---(b)(4)-- RBC . Please provide data to validate the usage of ----(b)(4)--- RBC for HA titering of H3 and B strains.
4. In “Post-approval Stability Protocol and Stability Commitment” (Section 3.2.P.8.2), you proposed that “only one batch will be placed on stability if it is the same strains as previous year”. We recommend that three batches of commercial product be placed on stability annually regardless of whether there are the same or new strains.
Regarding the Marburg Facility
5. Please provide the number of purification runs that were processed through the resins prior to your cleaning validations of the ----(b)(4)-------- columns. Was the number of these purification runs evaluated as part of your risk assessment before executing your cleaning validation for these columns? If so, please provide your risk assessment. If not, please provide your rationale for selecting the number of purification runs processed prior to your cleaning validation.
6. Please provide your plan to detect and prevent column fouling. Please describe how you will demonstrate that impurities do not leach from columns during subsequent production runs.
7. We strongly recommend that you perform ---------------(b)(4)------------ testing or another suitable test method during routine production after cleaning the ----(b)(4)-------------- columns and during periodic monitoring. You may want to consider testing samples for (b)(4) after every (b)(4) run when you are testing the performance of the column. Please also provide what acceptance criteria you would be using. Please note that in your cleaning validation your acceptance limit for the (b)(4) column was ---(b)(4)----. This acceptance limit would not be appropriate for your periodic monitoring.
8. Please provide your facility cleaning procedure to be implemented between pandemic and seasonal influenza vaccine manufacture. Additionally, please clarify if you monitor for potential residual pandemic viruses in your facility as part of the change over process after a pandemic vaccine campaign.
9. Please provide the trivalent bulk shipping validation (bulk shipment from Marburg to Rosia) protocol and report. Section 3.2.P.3.5.5. “Transport validation for formulated bulk” only provides the final product shipping validation.
Regarding the (b)(4) Facility
10. In Section 3.2.A.13.7.5 (Equipment cleaning section) you stated that your -(b)(4)- acceptance limit following cleaning is ------(b)(4)------ for your filling machine parts and other product contact equipment (for example ------(b)(4)----------. We find this limit is too broad for the shared/product contact equipment used in the filling process ------------------(b)(4)------------------. Please provide your rationale for establishing this limit, explain the possible source of this allowable --(b)(4)---------- and include your risk assessment for establishing this limit.
11. Please provide the most recent aseptic filling (syringe filling on --(b)(4)-- in building (b)(4) media fill protocol and summary report (for media fill conducted after May 2010).
12. Please provide an environmental monitoring summary report for the last three months of environmental monitoring including all deviations and corrective actions for Building (b)(4).
13. Please provide the validation protocol and summary report for the automated inspection machine (fill syringe inspection machine) and qualification protocol and summary report for the -------------------(b)(4)----------------- system.
Please submit the requested information as an amendment to STN 125408. 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.
Timothy A. Fritz, Ph.D.
1451 Rockville Pike
Rockville, MD 20852
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