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Vaccines, Blood & Biologics

Record of Telephone Conversation - July 23, 2009 - Prevnar 13

System Info - 113171  SMITH, MICHAEL J  08-Dec-2009 15:35:25  SMITHM


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

Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Wyeth Pharmaceuticals Inc.          

Telecon Date/Time:  23-JUL-2009 07:52 PM     Initiated by FDA?  Yes
Telephone Number:    

Communication Categorie(s):


Telecon Summary:
RE: Email for consult review request from J. Vaillancourt to S. Rubin and P. Krause on mumps and varicella assays.

FDA Participants:   Steve Rubin, Phil Krause, Tina Khoie, Lucia Lee and Julie Vaillancourt

Non-FDA Participants:   

Trans-BLA Group: No

Related STNs:  None

Related PMCs:  None

Telecon Body:
From: Vaillancourt, Julienne
Sent: Thursday, July 23, 2009 7:52 PM
To: Rubin, Steven; Krause, Philip
Cc: Khoie, Tina; Lee, Lucia
Subject: request for consult review on Prevnar 13 BLA (STN 125324)
Re: Request for review consultation on data in Prevnar 13 BLA concerning mumps and varicella assay and response data

Dear Steve and Phil,
Would either of you, or perhaps both of you, if you share the work somehow, be willing to take a look at the assay data for the mumps and varicella assays provided in Wyeth’s BLA for Prevnar 13 (STN 125324) and immunogenicity data for these two concomitant antigens from the pivotal phase 3 immunogenicity study to support this BLA.  Here is the situation:  the response to both antigens was low across both arms in the study (i.e., the 13vPnC arm and the comparator Prevnar or 7vPnC arm).  See excerpt from final study report below:

At the prespecified levels of 1.10 I.V., 1.10 I.V., 15 IU/mL, and 1.09 I.V. for measles, mumps, rubella, and varicella, respectively, the proportions of responders were 96.4%, 76.5%, 91.9%, and 26.7% in the 13vPnC group and 97.1%, 72.9%, 90.7%, and 21.9% in the 7vPnC group, respectively, after the toddler dose. The differences were -0.8% (95% CI, -4.5 to 2.9), 3.6% (95% CI, -4.7 to 11.9), 1.2 (95% CI, -4.4 to 6.9), and 4.8% (95% CI, -3.4 to 13.0) for measles, mumps, rubella, and varicella, respectively. GMRs were 0.98 (95% CI, 0.86 to 1.11), 1.03 (95% CI, 0.90 to 1.19), 0.83 (95% CI, 0.65 to 1.07), and 1.01 (95% CI, 0.92 to 1.11) for measles, mumps, rubella, and varicella, respectively. 

In recent discussion with Wyeth I was told that they have since re-assayed stored sera for response to varicella antigen using a different assay than originally used.  Apparently Merck would not allow Wyeth to use their licensed varicella assay.  However, Merck has recently out-licensed it to PPD and as a result Wyeth now has access to it.  Wyeth explained that the varicella assay that was originally used and the one that resulted in the low response was really an inappropriate assay for measuring immune response to varicella vaccine for these purposes.  Anyway, Wyeth will be providing the results of the re-assayed sera using the newly available Merck varicella asay.  I would ask one of you to please look at the varicella assay validation data presently in the BLA and which pertain to the assay originally used and which resulted in the very low values, for your opinion on why the response was so low.  When they submit information about the new varicella assay I would also like to know your opinion about it.  Finally, it would be helpful if you were to look at the actual varicella response data from the pivotal study.  In addition, I would like to know if you have any thoughts on the low response rate to mumps and whether the assay used by Wyeth might have contributed to this. 

The information can be found by accessing the link to the BLA, which is:


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This brief, two-page document notes the following:

A FDA approved ELISA method is used for the detection and quantitative determination of IgG antibody to Measles (Rubeola), Mumps and Varicella-Zoster virus in human sera. The specific kits used are the CaptiaTM Measles IgG, CaptiaTM Mumps IgG and CaptiaTM VZV IgG manufactured by Trinity Biotech USA (Jamestown, NY).

The response data for mumps and varicella are provided in the final report for study 6096A1-004, which can be found in Module 5, as well as follows:


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Your expert opinion and review assistance on these items would be greatly appreciated.

Thank you.
Julie Vaillancourt
Chair, BLA 125324

Julienne Vaillancourt, R.Ph., M.P.H.
Captain, US Public Health Service
Regulatory Reviewer
Division of Vaccines and Related Products Applications
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research
US Food and Drug Administration

Phone:    301-827-5414
Fax:        301-827-3532

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