System Info - 101577 SHONE, DEANNA 06-Aug-2009 16:10:06 SHONEDE
RECORD OF TELEPHONE CONVERSATION
Submission Type: Original Application Submission ID: 125324/0 Office: OVRR
Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)
Wyeth Pharmaceuticals Inc.
Telecon Date/Time: 05-MAY-2009 Initiated by FDA? Yes
Author: COLLEEN SWEENEY
E-Mail: Comments from Dr. Dragunsky's preliminary review of data submitted to BLA concerning validation of polio neutralization assay and immune response to concomitantly administered polio vaccine among subjects in study 6096A1-3005
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
FOOD AND DRUG ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
Date: May 5, 2009
To: Carmel Devlin, Associate Director
Global Regulatory Affairs,
Wyeth Pharmaceuticals Inc.
From: CDR C. Sweeney, MS, Regulatory Coordinator
CC: Eugenia Dragunsky,Ph.D.,DVP, Product Reviewer
Robin Levis, Ph.D., DVP
Konstantin Chumakov, Ph.D., DVP
Steven Rubin. Ph.D., DVP
Julienne Vaillancourt, R.Ph., M.P.H.,Chair
Subject: CBER Immunoassay Comments on STN 125324
Please respond to the comments below from Dr. Eugenia Dragunsky, based on her preliminary review of data in your BLA concerning validation of the polio neutralization assay and immune response to concomitantly administered poliovirus vaccine among subjects in study 6096A1-3005.
The following comments pertain to the “polio neut sabin” document in section 22.214.171.124, “Bioanalytical and Analytical Methods for Human Studies”:
1. In section 2.1.1 (page 7), you state that all three polioviruses met the acceptance criteria for accuracy recovery (b)(4) of GMT’s being within (b)(4)dilution factor of the expected GMT). However, the data in Table 2-indicates that was not achieved for poliovirus type 3. Please clarify.
2. In section 2.1.3 (pages 7-8), you list tables 2-3 and 2-4. The data in these tables are difficult to interpret. For both tables, please define all column and row headings. In addition, for Table 2-3, please indicate what the entered data refer to (e.g., numbers 6, 7, 5, 8, 3, 2 etc.)
3. Please provide data demonstrating specificity of your virus stocks used in these assays. We prefer that this is demonstrated by cross-reactivity studies.
4. In regard to Table 2-5 in section 2.1.4 (page 9),we note the failures of the poliovirus types 2 and 3 neutralization assays to meet the prescribed acceptance criteria ----(b)(4)----of the samples having expected titers upon dilution). While we agree that the measured titers were very close to the expected titers, the acceptance criteria were nonetheless not met. Please provide additional data in support of adequate assay sensitivity.
5. In regard to Table 2-7 in section 126.96.36.199 (page 12), please describe the set-up of the table and clarify whether the different dilutions of sera shown in the first column were made from a single high titer serum or five distinct sera.
6. Please submit the following two documents to the file:
- Validation Report of Poliovirus Antibody -----(b)(4)---------- Test, Wyeth Vaccines, Research External Contractor Document. VR-ECD-10012.
b. Poliovirus Antibody -----------(b)(4)------- Test ((b)(4). Protocol) Wyeth Vaccines Research, External Contractor Document. VR-ECD-10011.
The following comment pertains to information in the study report body for Clinical Protocol 6096A1-3005-US (section 188.8.131.52.3):
7. In Section 6.5.1 (page 27) we note apparent incorrect reference to use of a (b)(4)neutralization assay in measuring poliovirus antibody responses and apparent incorrect reporting of these antibody responses as IgG titers in Table 9.7 in section 184.108.40.206 (page 70). Please confirm these apparent errors and correct them, as follows:
- In section 6.5.1, it should be indicated that a -----(b)(4)---------- assay (not a (b)(4) neutralization assay) was performed.
b. In table 9.7, section 220.127.116.11, the presented titers should be described as neutralization titers in footnote “a”.