
Record of Telephone Conversation, July 23, 2012 - Flucelvax

 
 

Date/Time of Call:                             July 23, 2012 @ 9 AM

 

CBER Representative:                    

Ellen Huang, CSO, CBER/OCBQ/DMPQ/MRBII

Anissa Cheung, CSO, CBER/OVRR/DVP

Pete Amin, Reviewer, CBER/OCBQ/DMPQ/MRBII

Chiang Syin, Branch Chief, CBER/OCBQ/DMPQ/MRBII

Zhiping Ye, Research Microbiologist, CBER/OVRR/DVP/LPRVD

Xianghong Jing, Visiting Associate, CBER/OVRR/DVP/LPRVD

Brenda Baldwin, Microbiologist, CBER/OVRR/DVRPA/CMC3

Tim Fritz, CBER/OVRR/DVRPA, Microbiologist, CBER/OVRR/DVRPA/CMC2

Tim Nelle, Sr. Supervisory Regulatory, CBER/OVRR/DVRPA/CMC2

 

Organization Representative:         

Matthew Gollwitzer, Regulatory

Umang Shah, Regulatory

John Barry, Regulatory

Kerstin Platz, Regulatory

Manfred Brunen, Tech Transfer

Karsten Kattmann, Technical Operations

Tibor Nemes, Quality

Stefan Knapp, Quality Assurance

Martina Papadopoulos, Manufacturing

Josef Schulze, Process Manager

Peter Voelker, Quality Assurance

Michele Schmitt, Validations

 

Organization:                                    Novartis Vaccines and Diagnostics

                                                            

Telephone:                                         -----------(b)(4)----------------------------------------------

 

Subject:                                              BLA STN 125408/0, Responses to 483 items in Amendment 15

 

STN:                                                   STN 125408/0

                        

 

We contacted Novartis to discuss the firm’s responses to Amendment 15. The following information request questions were relayed to the firm.

 

1)      Regarding Observation 5A and US-OPF-015-1: Please clarify if ---(b)(4)--- goes into the       ------------(b)(4)------------.

2)      Regarding Observation 5B and US-OPF-015-2:

 

A)    Please clarify the source of the condensation observed in the collection bottle during the inspection (i.e. autoclave or ----(b)(4)-------).

B)    You stated that the autoclave parameters have been optimized as a corrective action and that it has been qualified. Please provide the qualification of autoclave.

C)    Please clarify what corrective actions have been implemented to reducing condensation in the fermentors ------(b)(4)-------.

D)    What procedural controls have you put in place to ensure you are reducing condensation?

 

3)      Regarding Observation 5C and US-OPF-015-2: From the lifetime studies, it appears that you have modified your cleaning and regeneration procedure for the (b)(4) column.

 

A)    Please specify when you have implemented the new cleaning and regeneration process for the (b)(4) column (------------(b)(4)-----------------).

B)    Please note that if this change was not reported to the Agency previously, it should have been reported as an amendment. Changes to your process need to be reported because we are basing our review on what has been submitted. Please clarify if there have been any other changes that have not been reported to the Agency.

C)    Please provide data to support these changes by demonstrating a reduction in bioburden in the cleaning evaluation sample.

D)    Please provide the SOP for the cleaning and regeneration process (including the sanitization run).

E)     Please provide the reagent(s) used in the sanitization run and the frequency of the sanitization run during normal production process.

F)     Please clarify the total volume of --(b)(4)- used for the storage of the (b)(4) column. Please also clarify if there is any change in the storage hold time of --(b)(4)-- in the column and specify the storage hold time.

G)    Please provide the re-validation data for the cleaning and regeneration of the (b)(4) column after these changes were implemented.

H)    Please specify how many batches were produced after the implementation of these changes.

I)       Please justify that all the proposed changes (---------------------------------------------------------------------------------(b)(4)------------.) in the cleaning and regeneration of the (b)(4) columns have no significant impact on the ongoing lifetime validation studies of the column.

 

Call Ended at 9:40 AM