http://www.fda.gov/cber/approvltr/diphave012903L.htm

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448

January 29, 2003

Submission Tracking Number (STN): BL 103919/5018

Luc Kuykens, M.D.
Aventis Pasteur, Inc
Discovery Drive
Swiftwater, PA 18370

Dear Dr. Kuykens:

The Supplement to your Biologics License Application for Diphtheria and Tetanus Toxoids Adsorbed (DT), for Pediatric Use, to include addition of a preservative-free, single dose vial presentation has been approved.

Under this approval, lots of single dose preservative-free DT Adsorbed shall have an expiration dating period of 24 months when stored at 2-8 0C. Any requests to extend the dating period beyond 24 months will require the submission of supporting data as a Supplement to your License Application for review and approval.

We acknowledge the following commitments outlined in your letter dated January 21, 2003:

1. You have agreed to accumulate real time stability data on final containers for lot ----- at the following intervals: 9, 12, 18, 24, 30, and 36 months, and these stability data will be provided to CBER as they become available. In addition, stability data on bulk vaccine lot ------ will be provided to CBER at the 9, 12, and 15 month time points as soon as those data are available.

    

2. You have agreed to add two additional lots of single dose preservative-free DT Adsorbed to your current stability program as they are manufactured. You have indicated that the approximate dates of manufacture for these lots are ---------------- and -----------------.

    

3. You have agreed to perform additional validation studies on the manufacturing process for the DT Adsorbed vaccine as outlined in the protocol contained in your submission of October 4, 2002. These validation studies will be conducted for two additional lots of single dose preservative-free DT Adsorbed vaccine with projected dates of completion in the second quarter of 2003.

    

4. You have agreed to withhold release of final container lot ---------- to the market until assay results for aluminum content have demonstrated that this lot meets the final container aluminum release specifications, and the results of the aluminum assay for this lot have been submitted to CBER for review.

    

5. You have agreed to submit a revised package insert for single dose preservative-free DT Adsorbed as a Prior Approval Supplement containing additional changes unrelated to removal of thimerosal.

Please submit four copies of final printed labeling at the time of use and include the label transmittal form FDA 2567 (6/01) with completed implementation information.

This information will be included in your License Application file.

Sincerely yours,

--- signature ---

Richard I. Walker, Ph.D.
Director
Division of Bacterial, Parasitic
    and Allergenic Products
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research

Last Updated: 3/25/2003