
Information Request Email, CMC issues, October 24, 2014 - BEXSERO

 

 
RECORD OF TELEPHONE CONVERSATION

Submission Type: BLA     Submission ID: 125546/0     Office: OVRR 

Product:
 Meningococcal Group B Vaccine 

Applicant:
 Novartis Vaccines and Diagnostics, Inc. 

Telecon Date/Time: 24-Oct-2014 02:47 PM     Initiated by FDA? Yes

Telephone Number: 

Communication Categorie(s): 
1. Information Request

Author: KIRK PRUTZMAN
Telecon Summary: 
IR regarding CMC issues

FDA Participants: KIRK PRUTZMAN, ED WOLFGANG, RAMACHANDRA NAIK

Non-FDA Participants: PATRCIA STOEHR

Trans-BLA Group: No

Related STNs: None

Related PMCs: None

Telecon Body: 


From: Prutzman, Kirk C 
 Sent: Friday, October 24, 2014 2:47 PM
 To: Stoehr, Patricia (patricia.stoehr@novartis.com)
 Cc: Wolfgang, Edward; Naik, Ramachandra
 Subject: STN 125546 - Information Request

Dr. Stoehr,

Please find attached a request for additional information regarding STN 125546 (Meningococcal Group B Vaccine). Please provide your responses to this information request in an Amendment to STN 125546 by November 7, 2014. If you have any questions about this communication, please contact Kirk Prutzman, Ramachandra Naik, or Ed Wolfgang at (301) 796-2640.

Regards,

Kirk Prutzman, PhD
 Primary Reviewer/Regulatory Project Manager
 CBER/OVRR/DVRPA/CMC3 
 Food and Drug Administration
 10903 New Hampshire Avenue
 Building 71 and Room 3041
 Silver Spring, MD 20993-0002
 Phone: (301) 796-2640
 Fax: (301) 595-1244


CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
 OFFICE OF VACCINES RESEARCH AND REVIEW
 DIVISION OF VACCINES AND RELATED PRODUCTS APPLICATIONS

DATE: OCTOBER 24, 2014       PAGES: 6

TO: NOVARTIS VACCINES AND DIAGNOSTICS, INC

ATTENTION: PATRICIA STOEHR, PH.D.
 Senior Group Manager Regulatory Affairs
 Novartis Vaccines & Diagnostics

350 Massachusetts Avenue
 Cambridge, MA 02139 
 USA

FAX: (617) 871-4711       TEL: (617) 871-8060

FROM: KIRK PRUTZMAN, PH.D.
 Regulatory Project Manager
 FAX: (301) 595-1244       TEL: (301) 796-2640

SUBJECT: STN: BL 125546/0  Request For Information 

MESSAGE:

Dear Dr. Stoehr:

We have the following request for additional information regarding your submission of Biologics License Application STN 125546 (Meningococcal Group B Vaccine):

 Regarding the OMV Drug Substance
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2. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------. 
3.-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
4.----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)--------------------------------------------------------.

 -------------(b)(4)------------------ 
5. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
6. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
7. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
8.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.

---------(b)(4)---------------- 
9. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -----

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------. 
10.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
11.------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
12.------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.

----------------(b)(4)--------------
13.----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
14.----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ----------------------------------------------(b)(4)-----------------------------------------------------------------.
15.--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
16.------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
17.---------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------. 

Regarding the Drug Product
18. Please provide a list of all hold times used in the manufacture of drug product. We note that in Section 3.2.P.3.5 Process Validation and/or Evaluation, formulation validation report MNNZ_FORMULATION02342PVR03 you did not provide in-process control results for the Sterility Test of -----(b)(4)------------- or for the Sterility Test of --(b)(4)-- as outlined in Section 3.2.S.P.3.3 Manufacturing Process and Controls [4CMenB  Suspension for Injection in PFS]. Please provide data to support these In-Process Controls.
19. Please provide a list of all filters used in the manufacture of drug product. We note in Section 3.2.P.3.5 Process Validation and/or Evaluation, --(b)(4)-- Validation Report Project No. 8-28-9786 that you provided extractable and leachable studies on the ------(b)(4)--------------- filter. If other filters are used in the manufacture of DP, please provide a justification as to why this filter represents worst case scenario with regard to E/L. Please provide extractable studies with different solvents to include water, ethanol, high pH, and low pH. Alternatively, please provide a justification for not using these solvents. Please provide leachable data using product testing for any material detected during the extractable studies.
20.We note that in Section 3.2.P.5.6 Justification of Specifications [4CMenB  Suspension for Injection in PFS] you have requested an exemption for the General Safety Test (GST) as a release test for drug product. We do not concur with your proposal at this time. Please add the GST as a release test. You may submit a post approval supplement to request exemption from the GST once an adequate amount of lots have been manufactured and tested. 

 Regarding Aluminum Hydroxide
21.Please provide the source of Aluminum Hydroxide. If this is not a purchased raw material, please provide details on the manufacture and stability. 

Please provide your responses to this information request in an Amendment to STN 125546 by November 7, 2014. 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 about this communication, please contact Kirk Prutzman, Ramachandra Naik, or Ed Wolfgang at (301) 796-2640.
