
Information Request Email, Potency Assay, July 15, 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: 15-Jul-2014 04:08 AM     Initiated by FDA? Yes

Telephone Number: 

Communication Categorie(s): 
1. Information Request

Author: KIRK PRUTZMAN

Telecon Summary: 
IR regarding the Potency Assay

FDA Participants: KIRK PRUTZMAN, ED WOLFGANG, RAMACHANRA NAIK

Non-FDA Participants: PATRICIA STOEHR

Trans-BLA Group: No

Related STNs: None

Related PMCs: None

Telecon Body:


From: Prutzman, Kirk C 
 Sent: Tuesday, July 15, 2014 4:08 PM
 To: Stoehr, Patricia (patricia.stoehr@novartis.com)
 Cc: Wolfgang, Edward; Naik, Ramachandra
 Subject: STN 125546 Information Request

Dr. Stoehr,

We have the following request for additional information regarding STN 125546 (Recombinant Meningococcal Group B Vaccine):

The following comments pertain to the document entitled: ----------------------------(b)(4)---------------------------------- Potency Assay (4CMenB – Suspension for Injection in Pre-filled Syringes), submitted in Section 3.2.P.5.3.
1.Please provide Validation Report 290462 VR1 describing the validation of the ---(b)(4)--- method 290462. Please include the individual --(b)(4)-- titer data used to estimate the relative potencies in that report in a readable file format. 
2. Regarding the ability of the (b)(4) potency assay to detect changes in the immunogenicity of ---(b)(4)------- final drug product, please provide the -(b)(4)- titer data used to generate Figures 3.2.P.5.3.2-1, 3.2.P.5.3.2-2, 3.2.P.5.3.2-3, 3.2.P.5.3.2-4 and Tables 3.2.P.5.3.2-3, 3.2.P.5.3.2-4. Please also provide the individual serum bactericidal titers used to generate Figures 3.2.P.5.3.2-5, (a) though (d). Please provide all data in a readable file format.
3.Please provide the -(b)(4)- titer data for ---(b)(4)----, used to generate the summary in Table 3.2.P.5.3.3-1 estimating the number of OOS, OOL and invalid assays based on the calculation methods tested. Please verify the system suitability criteria used to invalidate assays for each calculation method. Please provide the data in a readable file format and fully annotated.
4.Please verify that the geometric mean titer (GMT) of all (b)(4) in the group was used to generate the dose response curves used for relative potency. Please describe how non responders are handled in the estimation of the GMTs.

The following comments pertain to -(b)(4)--OMV-NZ – --------------(b)(4)------------------ Potency Assay (4CMenB – Suspension for Injection in Pre-filled Syringes), submitted in Section 3.2.P.5.3., and -(b)(4)--rp ------------------(b)(4)---------------- Potency Assay (4CMenB – Suspension for Injection in Pre-filled Syringes), submitted in Section 3.2.P.5.3.
5.The reports include a range for the assay but no data are provided to support the range. Please describe how the range was determined.
6.No data were provided to support the lower limit of quantitation for the assays. Please describe on what basis the determination of responder versus non responder is made. 
7.Please provide exemplar raw (b)(4) data from a typical assay including the reference sera, and samples spanning the titer range of the assay for each of the four (b)(4). Please provide the data in a readable file format and fully annotated.

The following comments pertain to the stability data in section 3.2.P.8.3.
8.Please provide the raw (b)(4) titers from the (b)(4) potency testing for all time points for batches ------(b)(4)-------, and --(b)(4)--. Please include all data from all (b)(4) assays and potency tests that failed to meet the system suitability criteria. 
9.Please provide the raw (b)(4) titers from all -(b)(4)- potency testing for the lots used in study V72_41 A Phase 3, Randomized, Comparative, Multicenter Observer-Blind Study Evaluating the Safety and Immunogenicity of Novartis rMenB+OMV NZ Vaccine Formulated with OMV Manufactured at Two Different Sites, in Healthy Adolescents Aged 11-17 Years. Please include all data from all (b)(4) assays and potency tests that failed to meet the system suitability criteria. 

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.

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
