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Vaccines, Blood & Biologics

Record of Telephone Conversation - September 3, 2009 - Prevnar 13

System Info - 113321  SHONE, DEANNA   09-Dec-2009 16:16:37  SHONEDE


Submission Type: Original Application   Submission ID:  125324/0    Office: OVRR  

Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Wyeth Pharmaceuticals Inc.

Telecon Date/Time:  03-SEP-2009 12:00 AM                Initiated by FDA?  Yes
Telephone Number:    

Communication Categorie(s):
Information Request


Telecon Summary:
RE: telecon with Wyeth regarding low response data on original mumps and varicella assays in Study 004, and seropositive cuttoff levels for rubella assay in Study 004.

FDA Participants:

Non-FDA Participants:   

Trans-BLA Group: No

Related STNs:  None

Related PMCs:  None

Telecon Body:



Record of Teleconference

Date/Time:September 3, 2009
File:BLA 125324/0
Product:Pneumococcal 13-Valent Conjugate (Prevnar plus Diphtheria CRM197 saccharide conjugates for Types 1, 3, 5, 6A,7F and 19A) Vaccine, Alum Adsorbed (Prevnar 13)
Sponsor:Wyeth Pharmaceuticals Inc.
Subject:Mumps, Varicella, and Rubella immunogenicity assays



Tina Khoie, M.D., M.P.H., Clinical Reviewer OVRR/DVRPA

Lucia Lee, M.D., Team Leader, OVRR/DVRPA

Philip Krause, Ph.D.  OVRR/DVP

Steve Rubin, Ph.D. OVRR/DVP/LMD

Judy Beeler, M.D., OVRR/DVP/LPRVD

Colleen Sweeney, M.S., Regulatory Coordinator, OVRR/DVRPA


Kathrin Jansen, PhD, Wyeth Pharmaceuticals Inc.

Dan Scott, PhD, Wyeth Pharmaceuticals Inc.

Carmel Devlin, Director, Global Regulatory Affairs

Background: CBER requested a meeting with Wyeth to discuss immunogenicity data regarding mumps, varicella, and rubella assays. The response to mumps and varicella antigens was low across both arms in the study (i.e., the 13vPnC arm and the comparator Prevnar or 7vPnC arm). A request for review consultation was sent on July 23, 2009, to Dr. Steve Rubin, Dr. Philip Krause, and Dr. Judy Beeler .

The following items were discussed during the present teleconference with the sponsor:

  • CBER informed Wyeth that the mumps non-inferiority (NI) endpoint was not met for the all available toddler immunogenicity population in study 6096A1-004 (CSR-69238). In addition, CBER asked for clarification as to why 35 subjects with lower mumps assay results were excluded from the evaluable population.
  • CBER requested further clarification regarding the Trinity Biotech Captia™ Mumps IgG enzyme-linked immunosorbent assay (ELISA) used for mumps analysis in Study 004. This assay is a diagnostic test indicated for determination of immune status from natural exposure.

Wyeth stated that a potential reason for the low varicella response may have been due to the commercial assay not having a matched strain. At the time, they did not have access to the assays used for licensing of the mumps component in ProQuad® (Merck and Co., Inc.). However, the Merck assay, which does have matched strains, is now available because Merck has recently transferred their vaccine immunology testing group to PPD Inc. This includes Merck’s proprietary varicella gpELISA and MMR assays.

  • CBER requested clarification regarding the pre-specified 15 IU/mL versus 10 IU/mL cutoff for the rubella data in study 004. Using the 10 IU/mL cutoff value (evaluable immunogenicity population), the difference in proportions is -1.3% (95% CI -5.9%, 3.2%). Therefore, the rubella responses did not meet the -5% noninferiority criterion when using the 10 IU/mL cutoff.

CBER requested the following items be submitted to BLA 125324:

  1. Full validation report for the Merck and Co., Inc. assays.
  2. Lot numbers for mumps and varicella vaccines used in study 6096A1-3005.
  3. RCDC’s for the varicella data from study 6096A1-3005.
  4. An analysis of rubella data using the 10 IU/mL cutoff.
  5. Mumps immunogenicity assays performed on remaining sera using Merck and Co., Inc. assay) obtained 1 month after the toddler dose for all subjects in the 7vPnC group and for a randomly selected subset of equal number of subjects from the 13vPnC groups (combined 13v lots) from study 6096A1-3005.
  6. Please re-analyze the rubella data from study 6096A1-004 at 10 IU/mL instead of 15 IU/mL, which were included in the clinical study report.

Contact FDA

(800) 835-4709
(240) 402-8010
Consumer Affairs Branch (CBER)

Division of Communication and Consumer Affairs

Office of Communication, Outreach and Development

Food and Drug Administration

10903 New Hampshire Avenue

Building 71 Room 3103

Silver Spring, MD 20993-0002

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