
Information Request Email, Rosia Facility and CCIT, October 6, 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: 06-Oct-2014 10:57 AM     Initiated by FDA? Yes

Telephone Number: 

Communication Categorie(s): 
1. Information Request

Author: KIRK PRUTZMAN

Telecon Summary: 
IR regarding Rosia Facility and CCIT

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: Monday, October 06, 2014 10:57 AM
 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 17, 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 6, 2014       PAGES: 4

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 information about your Rosia Facility contained in STN 125546 (Meningococcal Group B Vaccine):

 Regarding Receipt of Bulk Proteins
1. Please provide a summary of the verifications performed at receipt for the --(b)(4)-- Recombinant Proteins; Reference any applicable Standard Operating Procedures. 

 Regarding HVAC Systems
2. Reference 3.2.A.1.4.2 Drug Substance – OMV Manufacture (Rosia), Section 3.2.A.1.4.2.4, HVAC Systems and 3.2.A.1.4.3 Drug Product – Formulation-Filling-Finish, Section 3.2.A.1.4.3.4, HVAC Systems:
a.For the PQ studies for ---(b)(4)---, and (b)(4); and -(b)(4)-, numerous Surface environmental monitoring excursions were reported. Were root causes identified for these events and have you recognized a trend in these excursions? 

For each of these excursions, you state a subsequent resampling as a resolution and then reference closing of DRs on some previous date. 

For example in Table 3.2.A.1.4.2.4-15 HVAC System (b)(4) Test Results - Closed on January 09th 2012, you reference “Deviation (b)(4)-Surface environmental monitoring’s out of limit on point -------------------------(b)(4)------------------------ than acceptance criteria. Subsequent resampling within limits permitted closing of DRs on February 13th 2008.”  

Please explain what the date (in this example Feb 13th 2008) is referencing. 
b. You have provided no EMPQ data for (b)(4) HVAC System serving the Class (b)(4) Cold Room. Do you perform EMPQ for this room?
c. In Table 3.2.A.1.4.2.4-20 & -21, you cite areas that are classified as “Class (b)(4) (Exposed Product)”. Please identify the specific rooms where exposed product occurs, the extent of product exposure, and mitigation of risk that has been performed. 
3.Please confirm that --(b)(4)-- Formulation and Filling Areas supplied HVAC systems ---(b)(4)--- will not be used for Bexsero operations. 

Regarding Pharmaceutical Gases
4. Reference Process Air Systems in ---(b)(4)---: Please confirm that no Process air is exposed to product or product contact surfaces in Class (b)(4) or Class (b)(4) areas.
5.Reference Table 3.2.A.1.4.2.5.2.3-2, Performance Qualification Results for (b)(4): How did you establish the acceptance criteria for Microbiological gas? Why are they considerably higher than what your system appears to be able to maintain?

Regarding Cleaning Validation
6. In Table 3.2.A.1.4.2.6.1.9.2-1: Types of Residues and Method of Detection, you provide the potential residues, but do not state which residue was the most difficult to clean, and the Method of detection used for that residue. Please provide this information.
7.Please provide a table of the Clean and Dirty Hold times that you have established for the OMV product contact equipment.
8.Please provide the rationale for your -----(b)(4)---------------------------- limits for all product contact equipment using a cleaning procedure with a WFI final rinse.
9.Please provide a rationale for your (b)(4) limit of -(b)(4)- including how it equates to a parts per billion (ppb) calculation and why it is acceptable for every piece of equipment even though they have different surface areas.
10.Reference Table 3.2.A.1.4.3.7.1.10-2, Current Specifications for the Cleaning Validation” You state that the -----------------------------------------(b)(4)----------------------------------- records the optimal condition for ------------------------(b)(4)---------------------. However, your current CV specification for ----(b)(4)---- is --(b)(4)--. Please provide your justification for the limit. 

Regarding OMV Bulk Container
11.Please provide a summary of the OMV Bulk Container CCIT validation with reference to relevant protocols.

Regarding Drug Product Container Closure
12.Please confirm that the Luer Lok (b)(4) syringe will be used solely for commercials product, or do you plan to use the Luer --(b)(4)-- syringe alternatively, as needed?
13.Please provide a summary of the CCIT validation with reference to relevant protocols.
14.Was functionality testing of the syringe system(s) performed? If so, please provide a summary of the study. 

Regarding OMW Bulk Production
15.Please confirm that all OMV bulk will be produced at the Rosia site for commercial product.

Regarding Filling Validation 
16.Reference Table 3.2.P.3.5.1.2.2-7; ODMS Rejection Rate Verification: Please explain why your rejection rate acceptance -(b)(4)- is almost tenfold higher than your rejection rate acceptance (b)(4) for the --(b)(4)-- Filling Validation (2011).

Regarding Product Stability
17.Will Container Closure Integrity Testing (CCIT) be included in the Post Approval Stability Program for Final Filled Product (PFS)? If so, please provide the time intervals.

Please provide your responses to this information request in an Amendment to STN 125546 by October 17, 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.
