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Vaccines

Record of Telephone Conversation, August 20, 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: 20-Aug-2012 04:50 PM        Initiated by FDA? Yes
Telephone Number:
Communication Categorie(s):
1. Other - Assays inadequate
 
Author: BRENDA BALDWIN
Telecon Summary:
PS80 and CTAB method issues
FDA Participants: Brenda Baldwin, Timothy Fritz, Timothy Nelle
Non-FDA Participants: Matthew Gollwitzer
Trans-BLA Group: No
 
Related STNs: None
Related PMCs: None
E-mail Body:
From:     Baldwin, Brenda 
Sent:                      Monday, August 20, 2012 4:50 PM
To:                         Gollwitzer, Matthew
Cc:                         Fritz, Timothy
Subject:                 FW: --(b)(4)--- for Optaflu, STN: 125408
 
Hi Matt,
 
To aid in the discussion tomorrow, I have the following review narrative for the CTAB and PS80 problem areas that will need to be forwarded to the appropriate people at Novartis.
 
Based on the review of the test methods and the validation reports, DBSQC concludes that the methods used for the determination of polysorbate 80 and CTAB are inadequate for their respective intended use. 
 
Quantification of Polysorbate 80 in FCC Vaccine ---(b)(4)----- using –(b)(4)----
 
 
 
 
 1 Page Determined to be Not Releasable: (b)(4)
 
 
  
As such the method validation results meet acceptance criteria, except for Specificity of the polysorbate 80 assay. However, since the method itself is not appropriate, such validation results do not have significance. It is recommended that NVD conducts additional studies to characterize ---(b)(4)------ obtained by ---(b)(4)----- for the quantitation of polysorbate 80 to show that there is no change in --(b)(4)-- due to the process steps and that the --------(b)(4)------------------------------ are solely due to polysorbate 80. NVD should also use (b)(4) area as the criterion of the quantitation. Alternatively, they could develop a different method for this purpose.
 
---(b)(4)------- Determination of CTAB (Cetyltrimethylammoniumbromide) in FCC Vaccine ---(b)(4)---
 
Review indicates that the -------(b)(4)------------------------- polysorbate 80 has significant influence on the results of the ---(b)(4)---- assay for the determination of CTAB. It appears that most of the contribution is coming from the (b)(4). Document No. 264131-01 (Attachment 8 to Quality Information Amendment, 125408/0.12) reports results of analysis by linear regression analysis of (b)(4) lots of FCC ---(b)(4)-------- materials, ----------------------(b)(4)-----------------------------------------------------------------------------------------------------------------------------------------------------------:
                                                ----------(b)(4)------------                                                                                                            
-----
--------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
 
-------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------(b)(4)----------------------------------------------------------------------------
------------------------------------------------------(b)(4)---------------------------------------------------------------                          
----
---------------(b)(4)------------------
-------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------. 
 
 
[(b)(4)]
 
 
 
 
 
 
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
-----------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)--------- of CTAB in samples. Thus, the acceptance criterion for Accuracy is not acceptable.
It is recommended that NVD develop an alternate assay for this purpose.                                         ----(b)(4)-------------- methods for the determination of CTAB have been reported in the literature. Method validation studies failed to demonstrate Specificity and Accuracy of the assay and Robustness study is not reported. Although, Repeatability and Intermediate Precision results met acceptance criteria, there are some issues as discussed above. Thus, it is concluded that the method has not been validated appropriately.
 
We recommend that NVD develop an alternate assay for this purpose and validate the new method. ------(b)(4)--------- methods for the determination of CTAB have been reported in the literature. Furthermore, method validation studies failed to demonstrate Specificity and Accuracy of the assay. Thus, it is concluded that the method has not been validated appropriately.
 
Regards,
Brenda