System Info - 111989 SMITH, MICHAEL J 24-Nov-2009 12:59:01 SMITHM
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: 24-NOV-2009 12:53 PM Initiated by FDA? Yes
Author: MICHAEL SMITH
Email: CBER's comments and requests regarding the planned phase 4 safety study to be conducted at NCKP (protocol # 6096A1-4002)
FDA Participants: Mike Smith and Julienne Vaillancourt
Non-FDA Participants: Jack Love and Carmel Devlin
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
From: Smith, Michael (CBER)
Sent: Tuesday, November 24, 2009 12:53 PM
To: 'Love Jack'; Devlin Carmel
Cc: Vaillancourt, Julienne
Subject: RE: CBER's comments and requests regarding the planned phase 4 safety study to be conducted at NCKP (protocol # 6096A1-4002)
Jack and Carmel,
Dr. Marthe Bryant of the Prevnar 13 review team has the following comments and requests regarding the planned phase 4 safety study to be conducted at NCKP (protocol # 6096A1-4002).
1- The November 18, 2009, Advisory Committee raised some concern about the potential risk for autoimmune disease associated with the increased dose of CRM protein with each injection of Prevnar 13 in the infant series.
- In order to better assess the safety of Prevnar 13, the committee requested that you add arthralgias to the list of pre-specified events of interest for analyses.
- The committee also requested that you include recipients of organ transplants in the list of children with immunosuppressive conditions.
- To reduce our risk of missing associations with adverse events that have longer onset intervals, we recommend adding self-controlled screening analyses in step 1 with 60 day risk windows in addition to the previously planned 30 day windows.
- Because the current draft protocol calls for omission from analyses of a vaccinee's second or subsequent seizure or other potentially recurrent adverse event, we recommend specific supplementary interim and final analyses to identify possible positive rechallenges that may warrant further evaluation.
Please make the corresponding revisions in the study protocol.
In addition, the advisory committee's recommendation that organ transplant recipients be included among the immunosuppressed subset raised a question for us. How can we be confident in the comprehensiveness of your list of diagnoses to identify definitely or possibly immunodeficient patients? One option might still be to take advantage of the actual pharmacy prescription or dispensing data files. An alternative might be to generate a frequency distribution of diagnoses from a pharmacy file for immunosuppressive drugs. This list of diagnoses could then be examined to assure that no important diagnoses are being overlooked. Please address this issue in your protocol revision.
2- We appreciated your response to one of the advisory committee members to the effect that this Kaiser Permanente database study will have ample capacity for evaluation of potential risks with much longer latencies. We recommend that further analyses be planned with risk windows of more than 60 days, potentially as much as 6 months or more, in response to particular signals that may emerge after licensure, whether from the acute safety study, VAERS, or other sources.
Please let Julie and I know if there are any questions.
Mike Smith, Ph.D.
Lieutenant Commander (LCDR), U.S. Public Health Service
Regulatory Project Manager
Division of Vaccines and Related Products Applications
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research
U.S. Food and Drug Administration
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