
Information Request Email, CMC issues, October 8, 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: 08-Oct-2014 12:32 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: PATRICIA STOEHR

Trans-BLA Group: No

Related STNs: None

Related PMCs: None

Telecon Body: 


From: Prutzman, Kirk C
 Sent: Wednesday, October 08, 2014 12:32 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 October 31, 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 8, 2014       PAGES: 7

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

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):

 The following comment pertains to the Drug Product used for the clinical studies submitted to this Biologics License Application
1. In section 3.2.P.5.4 Batch Analyses, General Manufacturing Information and Batch Analysis results are provided for Lot 101601. Please provide this information for the following additional clinical lots used in the studies submitted to this application: 090101, X38D27N1, X38D28N1, and X38D29N1. In addition, please provide the in-process and release data for all DS lots used in DP lots 101601, 090101, X38D27N1, X38D28N1, X38D29N1, and 126501 (used in Princeton and UCSB). Please also include date and site of manufacture.

The following comments pertain to the OMV DS.
2. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------. 
3. -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.
4. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4) . 

Redact 3 pages (b)(4)
6. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4) . 
7.----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4) .

The following comments pertain to the Drug Product.
8.Justifications for the following Drug Product release test specifications for Final (b)(4), Filled, and Packaged Product are not adequate: ----------------------------------------------------------------------------(b)(4)------------------------------------------------------------- and pH. The justification provided in Section 3.2.P.5.6 “Justification of Specifications Table 3.2.P.5.6-1” is not adequate. While your justifications accurately state the purpose of these tests, your specifications do not reflect the analysis of your manufacturing process experience for any of the listed tests. Please revise the specifications to reflect historical performance of lots in the tests or justify how the specifications proposed are adequate to control the quality and consistency of the product. Please provide data and analyses using manufacturing scale lots for justification of specifications for these. Please provide the clinical experience ranges for each. 
9.Regarding your extractable and leachable studies, in Section 3.2.P.2.4.1 you describe extractable/leachable studies performed on ----(b)(4)---- syringes at your contract laboratory -----(b)(4)------. The study evaluated volatiles and semi-volatiles but did not investigate non-volatile leachable compounds or extractables. Please provide study data that uses an appropriate non-volatile matrix based on this drug product or a similar one, or justify the absence of this study. Also, please provide an appropriate extractables study or justify the absence of this study.

The following comment pertains to Comparability Protocols
10.Please confirm that no Comparability Protocols were submitted with this BLA to request a future change to be downgraded to an Annual Report. We note that you submitted a section in each DS subsection for qualification of future reference material (Section 3.2.S.5). The information provided in these sections does not include a detailed Comparability Protocol. A post approval supplement can be submitted to request a Comparability Protocol for downgrading future changes to Annual Report. Please confirm.

The following comment pertains to rp936-741 and rp287-953 DS
11.------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4) .

Please provide your responses to this information request in an Amendment to STN 125546 by October 31, 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. 
