System Info - 101574 SHONE, DEANNA 06-Aug-2009 15:59:21 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: 01-MAY-2009 12:00 AM Initiated by FDA? Yes
Author: COLLEEN SWEENEY
RE: E-mail Preliminary Clinical review comments from Dr. Tina Khoie
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
FOOD AND DRUG ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
Date: May 1, 2009
To: Carmel Devlin, Associate Director
Global Regulatory Affairs,
Wyeth Pharmaceuticals Inc.
From: CDR C. Sweeney, MS, Regulatory Coordinator
CC: Tina Khoie, M.D., M.P.H., Clinical Reviewer
Lucia Lee, M.D., Team Leader, VCTB, DVRPA
Julienne Vaillancourt, R.Ph.,M.P.H.,Chair
Subject: CBER Clinical Comments on STN 125324
Based on preliminary review of the clinical portions of your BLA (STN 125324), Dr. Tina Khoie has the following comments:
1. In your August 7, 2008, submission to IND ---(b)(4)--, you requested a partial waiver to study your vaccine in infants from 0 to < 2 months of age and a deferral to study it in children from 6 to 16 years of age. At that time you also proposed a plan for the deferral studies in the older pediatric age group. We have since had various discussions with you about aspects of the plan and as a result it has been revised. Please submit as an amendment to your BLA, the revised Pediatric Plan to justify this request per the Pediatric Research Equity Act (PREA), [21 U.S.C. 505B(355c)].
2. Please provide a letter of cross reference to the Prevnar Acute Otitis Media (AOM) sBLA, STN 103905.
The following items pertain to the clinical studies.
3. In regard to the safety tables submitted under study 004:
- Please clarify if the denominators used for the solicited events, e.g., % of subjects experiencing each solicited adverse event,reflect the total number of subjects that responded “Yes,” on at least one day, or “No,” for all days, for each indicated graded reaction.
b. Please clarify whether the term “any reaction,” reflects that a parent/legal guardian noted reactions, e.g., erythema, or tenderness, but did not provide sufficient information to grade the reaction.
c. Immediate reactions seem to be summarized in the table for unsolicited adverse events. Please explicitly state which events in this table occurred immediately, e.g., within 30 minutes, following administration of the product.
d. Please provide a line listing similar to Table 15.86 in the CSR69238-report-body document which includes subjects reporting local or systemic reactions lasting > 7 days.
4. The CSR69238-report body document includes a list of subjects with protocol violations that resulted in exclusion from the evaluable immunogenicity population. However, a line list of subjects with any protocol violation (e.g., minor or major protocol violations) is not provided. Please provide the following information for all subjects in study 004 with any minor or major protocol violation in a tabular/column format:
a. Subject identification number
b. Treatment group
c. Protocol violation (yes/no)
d. Description of protocol violation
e. Subject included in the evaluable immunogenicity population (yes/no)
f. Subject included in the safety analysis (yes/no).
If a protocol violation occurred, and the subject was still included in the evaluable immunogenicity and/or safety population, please include an additional column indicating the reason for inclusion, e.g., if the subject was compliant with the required blood draw interval.
5. You describe safety related study discontinuations as:
- Subjects who were withdrawn
- Subjects who permanently discontinued the study drug
- Subjects who were both withdrawn and had permanent study drug discontinuation
Please explicitly state the difference between subjects who were withdrawn and subjects who permanently discontinued the study drug.
6. To expedite CBER review, we please request that the following two RCDC figures be submitted for study 004 in a format that can be manipulated, e.g., Excel: one figure representing the RCDC curves for the 7 common pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), and a second figure representing the RCDC curves for the 6 additional pneumococcal serotypes (1, 3, 5, 6A, 7F, 19A).
7. Please submit a line list of all subjects excluded from the toddler all available immunogenicity population due to protocol deviations for study 003.
8. We note that the files “dai” and “milestn” are not listed in the define-listing file for study 004 and 009.
9. On pages 397 – 400, of the CSR-69238-report-body document, Serious Adverse Events are listed. Please submit the outcomes of these events.
10. Please explicitly define “forced” randomization.
11. Please provide the tables from the clinical study reports for studies 003, 004, 3005, 006, 008, 3002, and 009 in a format that can be manipulated, e.g.,Excel or Word.
Please note that if any of the requested files have been submitted, please provide the filename and location in the eCTD."