
Information Request Email, CMC Issues, December 12, 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: 12-Dec-2014 03:28 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: Friday, December 12, 2014 3:28 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 29, 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 12, 2014     PAGES: 5

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 29, 2014 or submit reasonable timelines for providing the requested information. 

 We have reviewed your responses to our Information Requests dated October 8, 2014, October 24, 2014, and November 6, 2014. We do not concur with all your responses. Please submit the following additional information by December 29, 2014. In addition, please provide a timeframe for any data being submitted post approval.

1. We have reviewed your response to Question 4 of our October 8, 2014 Information Request. Although your data support your revised specifications for the -------------------------------------------------(b)(4)--------------------------------------, we do not concur with your process validation for your ---(b)(4)---------- process in which you applied new specifications that were not in place at the time of the validation study. You describe the application of these revised specifications to the validation lots in 3.2.S.2.5 Process Validation and/or Evaluation ---(b)(4)------. Please repeat your process validation using your current specifications according to a pre-defined validation protocol. This study can be submitted post approval in the form of Product Correspondence.


2.We have reviewed your response to Question 8 of our October 8, 2014 Information Request. The material and that added in Amendment 0.31 in response to the November 26, 2014 teleconference, is acceptable to demonstrate that the ---(b)(4)------- is under control. During a Teleconference on November 26, 2014 with CBER, you acknowledged that the “Unspecified Impurities” as defined in the original submission was incorrect and that the current definition, supplied in your response is the correct definition. You have agreed that, due to this revised definition, -------(b)(4)----------- are not tractable as the current data is presented. You have agreed to propose release and stability specifications and submit data to support such specifications for the ----(b)(4)---------- test that separately accounts for ------------(b)(4)----------------------------------. Please provide these proposed specifications and data to support them.


3.We have reviewed your response to Question 9 of our October 8, 2014 Information Request. You have agreed to submit the updated -------(b)(4)------ Specification Report for ---------------------------------------(b)(4)--------------------------------------------------------. Please submit this report as a CBE supplement if you propose to tighten the specification, as a PAS if you propose to loosen the specification, or as Product Correspondence if you propose to not change the specification. 


4.We have reviewed your response to Question 11 of our October 8, 2014 Information Request. You have agreed to submit the updated -------------------------------------------------------------------------(b)(4)----------------------------------------------. Please submit this report as a CBE supplement if you propose to tighten the specification, as a PAS if you propose to loosen the specification, or as Product Correspondence if you propose to not change the specification.


5.We have reviewed your response to Question 12 of our October 8, 2014 Information Request. You have agreed to provide the ------(b)(4)---------------------- Control Specification Report for --------------(b)(4)--------------------. Please submit this report and proposed specification as a CBE supplement. 


6.We have reviewed your response to Question 14 of our October 8, 2014 Information Request. You have agreed to submit the updated ---------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------. Please submit this report as a CBE supplement if you propose to tighten the specification, as a PAS if you propose to loosen the specification, or as Product Correspondence if you propose to not change the specifications. 


7.We have reviewed your response to Question 15 of our October 8, 2014 Information Request. We do not concur with your proposal for a -----------------------------------------------------------------(b)(4)-------------------------------------------- is appropriate based on the information that you submitted. Please revise your request to a ----------(b)(4)------- limit. A maximum -----------(b)(4)---------- limit may be requested after supportive data from---- (b)(4) using manufacturing scale lots has been collected. This request should be provided as a Prior Approval Supplement.


8.We have reviewed your response to Question 16 of our October 8, 2014 Information Request. You have agreed to submit an updated ------(b)(4)----------------------- after analysis from a minimum of (b)(4) additional manufacturing scale lots. Please submit this report as a CBE supplement if you propose to tighten the specification, as a PAS if you propose to loosen the specification, or as Product Correspondence if you propose to not change the specifications. 


9.We have reviewed your response to Question 17 of our October 8, 2014 Information Request. Based on the information that you submitted, we do not concur with your proposal for -----------------------------(b)(4)------------------------------------------------ process. Please revise your requested resin reuse limit based on the commercial data submitted which appears to be -------------(b)(4)--------------------------------- respectively. A request to ------------(b)(4)------------------ can be submitted post approval after accumulation of supportive data from -------------(b)(4)--------------- generated on manufacturing scale lots. This request should be submitted as a Prior Approval Supplement.


10.We have reviewed your response to Question 21 of our October 8, 2014 Information Request and your related response to Question 2 of our November 17, 2014 Information Request. For rp287-953, you indicated that you had a relatively small data set from(b)(4) commercial lots available to evaluate the process capability and estimate specification limits precisely and you would reassess the process capability and specification once adequate number of data would be available. Please submit this report as a CBE supplement if you propose to tighten the specification, as a PAS if you propose to loosen the specification, or as Product Correspondence if you propose not to change the specifications.


11.We have reviewed your response to Question 1 of our October 24, 2014 Information Request. You propose to submit --(b)(4)-- validation data post approval. This is acceptable. Please perform your study using the following criteria: 1) The process is tested under worst case scenario conditions; 2) The tests used for each hold time outlined in Table 1-1 of your response must include all those listed in Tables 3.2.S.2.2.2-1 and 3.2.S.2.2.3-1 with the addition of ------------------(b)(4)-------------------------------------------------------------. Please submit this report as a Product Correspondence submission.


12.We have reviewed your response to Question 3 of our October 24, 2014 Information Request. You have not demonstrated control of (b)(4)------ or sterility for your --------------------(b)(4)------------. Please commit to repeat your ----(b)(4)-- hold time validation study to include -------(b)(4)--------------- post approval. Please submit this study as Product Correspondence as data for ----(b)(4)---------------- data points are available. 


13.We have reviewed your response to Question 5 of our October 24, 2014 Information Request. We do not concur that your ---(b)(4)---- times for --------------------(b)(4)------------------------------------------------------------------------------- are validated for -----(b)(4)---------------------. Please repeat your ---(b)(4)-- study to include evaluation of --------(b)(4)----------------- under worst case scenario post approval. Please submit this (b)(4) validation report as Product Correspondence,


14.We have reviewed your response to Question 14 of our October 24, 2014 Information Request. Your response provides a list of all filters used in the manufacture of -------------------(b)(4)---------- as requested. Your proposal to perform (b)(4) studies on the medium risk process filters identified in Table 6-2 in your response post approval is acceptable. Please provide the report as Product Correspondence. 


15.We have reviewed your response to Question 15 of our October 24, 2014 Information Request. Your response is not adequate. You state that updated ----------(b)(4)------------------------------------------------------- are provided in the updated Section 3.2.S.7.3 Stability Data ---(b)(4)------. However, the updated section was not found. Please provide this document. 


16.We have reviewed your response to Question 9 of our October 24, 2014 Information Request. Your response is not adequate. You have not provided -------(b)(4)---------------------------- validation of worst case scenario (b)(4) for capture ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------. Please repeat your hold time validation study evaluating for bioburden and endotoxin post approval. Please submit this study as Product Correspondence.


17.We have reviewed your response to Question 10 of our October 24, 2014 Information Request. You refer to your response to Question 6 of our October 24, 2014 Information Request where you commit to perform (b)(4) studies on the medium risk process filters used in production of --(b)(4)--. If your intent is to perform (b)(4) studies on filters identified in Table 10-1 post approval, this is acceptable. If this is not your intent, please clarify. If this is your intent, please submit the report as Product Correspondence.


18.We have reviewed your response to Question 16 of our October 24, 2014 Information Request. Your response is not adequate. The -----(b)(4)---------------- data presented in the updated Section 3.2.S.7.3 Stability Data ---(b)(4)-------------- contains data limited to 9 months. Please submit -----(b)(4)-------- data post approval for ---(b)(4)------- as Product Correspondence as the 12, 24 and (b)(4) month data are available. 


19.We have reviewed your response to Question 2 of your November 6, 2014 Information Request. Your proposal to update the range of the ------(b)(4)--------------------------- to include the range for unspecified impurities is acceptable. Please submit this as Product Correspondence.


 Please address the following Additional Request.

20.CBER has completed the ----(b)(4)-------- per your SOP (AP63.470, Edition 5.0) “Determination of identity and purity of MenB --------(b)(4)-----------------------------”. The resolution between the ---------------(b)(4)----------------------------- is significantly greater than (b)(4). According to your SST acceptance criterion “The resolution between the -------------------------(b)(4)-------------------------- has to be less or equal to (b)(4)” (Section 5.1), hence this SST check failed. However, we believe that this --(b)(4)-- acceptance criterion) is a typographical error in your SOP. It should be no less than (b)(4). Please confirm, make any necessary corrections and resubmit. If it is not the case, please justify acceptance criterion with supporting data.


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. 
