System Info - 107036 MCWATTERS, BERNARD 06-Oct-2009 17:02:21 MCWATTERS
RECORD OF TELEPHONE CONVERSATION
Submission Type: Original Application Submission ID: 125297/0 Office: OVRR
Novartis Vaccines and Diagnostics, Inc.
Telecon Date/Time: 14-AUG-2009 12:00 AM Initiated by FDA? Yes
Author: BERNARD MCWATTERS
IR about CMC, facility and clinical issues.
FDA Participants: Bernard J.P. McWatters
Non-FDA Participants: Joanne Totosy de Zepetnek
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
I have been checking in to the 3 questions that you asked me and have feedback on 2. Dr. Baylor could still not give me a clear answer on when your label would be ready to send, but she assured me that she is working on it. As far as the license number, the regulations are pretty clear that you need it printed on each of the items that you asked about, but you already have it. Your license number will be the same, even with the new product in a new facility.
The review of your complete response is finished and we have the following information requests:
- Your proposal to drop r2 as the validity criterion for -b(4)- method is not acceptable. We have not heard of any problem from other manufacturers about linearity and do not expect more than 10% assays fail the r2 criterion. A validity criterion which provides assurance of the fit of the analysis model is considered necessary. If you want, DPQ can share our-b(4)- test method and MS Excel calculation worksheet with you.
- If you are ready with this year manufacturing campaign, please submit b(4)lots of monovalent bulks of each of the 3 influenza vaccine strains for the 2009-2010 season to DPQ for testing. In addition, please also submitb(4) lots of trivalent formulated bulks from the commercial lots for 2009-2010 season before licensure. All these lots have to be submitted through PRB along with the lot release protocols we agreed upon (please see comment #4).
- Please submit letters from CBER confirming your vaccine strains for the 2009-2010 season.
- There seems to be some miscommunication on content of the lot release protocols. You have removed a lot of information from the LRP that we have communicated to be retained. We sent templates for specific tests that had to be inserted in the submitted LRP template. Instead you substituted your submitted LRP template with the CBER templates, which were for specific tests.
- Regarding CR Question #7: Please note that under this item we had requested you to provide information on b(4) testing and data in support of the extractable studies. You state at the bottom of Table 7-1 that the filters have been tested according to b(4) requirements. Please provide these reports and data.
- Regarding CR Question #9: Your assessment that the filters are equivalent to the --b(4)-- filter cannot be supported because your vaccine product was not used during the extractable testing for the ---b(4)---------------- filters. A Model --b(4)-- approach was used by b(4) manufacturers based on the assumption that --b(4)-------------------------------------------------------------------------------; however there is no information that the product was tested to evaluate the presence of interfering substances in the bulk vaccine product. You have adequate data to support the use of --b(4)--- filter; however, you need to perform additional extractable testing in the presence of product for the ---b(4)-------------- filters or provide scientific justification. The additional extractable data can be submitted as a CBE-30. Please note that these filters should not be used until such testing is completed.
- In CR Question #9, you were asked to provide your assessment used to determine equivalence between the filters; however, you did not include filter characteristics and processing parameters. Please provide a comparison of filters including these criteria.
- Please submit a pediatric study plan for the 6 months to 4 years old age group by no later than August 19 to enable required deliberations by the Pediatric Review Committee.
ADDITIONAL INFORMATION REQUEST
- Why did the 3-8 and 9-17 year old cohorts in Study V71P5 enroll only Caucasian subjects, while the 18-64 year old cohort enrolled 21% Hispanic and 79% Caucasian subjects?
- Please provide a time frame for submission of clinical study report for Study V58P4E2 which will evaluate the effect of concomitant polysaccharide pneumococcal vaccine in the elderly, and is reported as ongoing.
- Please provide final follow-up on the outcomes of all pregnancies that occurred in studies V71P5 and V71P6.
- With regard to your stated intention to provide enhanced surveillance of adverse events of interest, please provide a comprehensive list of all such events of interest for Agriflu, and indicate the time frame for submission of these additional data to FDA.
- Please submit a Pharmacovigilance Plan at the time of submission of the final reports for clinical efficacy study/studies (V71P7), incorporating any safety signals identified. This should also include safety signals identified in the review of clinical studies submitted in this BLA.
- Please provide plans for establishment of a pregnancy registry in the United States to prospectively collect data on spontaneously-reported exposures to Agriflu during pregnancy.
If you have any further questions, please feel free to contact me. If you need a lot of information or feel that it is necessary, the review team can be made available to have a teleconference about the items covered in this information request. Thanks for your attention and have a nice weekend.
Bernard J.P. McWatters, Ph.D.
1401 Rockville Pike rm. 379N
Rockville, MD 20852
Office - 301-827-3921