
Information Request Email, Endotoxin Testing, December 3, 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: 03-Dec-2014 02:55 PM     Initiated by FDA? Yes

Telephone Number: 

Communication Categorie(s): 
 1. Information Request

Author: KIRK PRUTZMAN

Telecon Summary: 
IR regarding Endotoxin Testing

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, December 03, 2014 2:55 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 the data requested by December 19, 2014 or submit reasonable timelines for providing the requested information. 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: DECEMBER 3, 2014     PAGES: 2

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 STN 125546 (Meningococcal Group B Vaccine). Please provide the data requested by December 19, 2014 or submit reasonable timelines for providing the requested information.
1. The currently proposed BET test used for release testing of ---(b)(4)--, DP Bexsero, and for the stability monitoring program of DP -(b)(4)-- appears to be adequate to support approval. However, we also note that the BET test is highly variable. Please provide additional method development and validation data to address the following:
a.That variability is controlled such that DP release specification is supported and justified.
b.That variability is controlled such that DP stability testing results in useful trending data that do not have recurring out-of-trend and OOS results.
c.That assay robustness, sample handling procedures, and testing sample dilution are included in the re-evaluation and optimization of this assay.


2.The relationship between (b)(4)---- endotoxin levels and endotoxin content levels reported in final DP does not appear to be consistent. Please comment.


3.The product release specification for Endotoxin Content of DP is upper bounded only and should be both upper and lower bounded. This becomes apparent upon review of product composition and release test data provided in amendment number 9 received September 2014.


4.The ---(b)(4)----- release specification for endotoxin content per microgram protein is upper bounded only and should be both upper and lower bounded.


5.Please clarify the history of changes to BET used for DP release and stability testing explaining the following:

a.The changes that were made and the date and purpose of each change. 
b.The version of the test used in each lot of product released.

6.Based on the data from the stability testing, the assay does not appear to be performing as validated. Please provide an analysis that compares the testing performed in support of the product stability with that performed during routine release testing. Please describe any differences with regard to testing dates, operators, equipment or system suitability results that might explain the increase in variability seen for the stability tests. Please include any changes to the assay made since validation.


Please provide your responses to this information request in an Amendment to STN 125546. 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. 
