Our STN: BL 125145/0
Sanofi Pasteur Inc.
Attention: Gary K. Chikami, M.D.
Associate Vice President, Regulatory Affairs, North America
Swiftwater, PA 18370-0187
Dear Dr. Chikami:
We have completed the review of your submissions to date to your biologics license application (BLA) for Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (PentacelT) for active immunization for the prevention of diphtheria, tetanus, pertussis, poliomyelitis and invasive Haemophilus influenzae type b disease, submitted under section 351 of the Public Health Service Act.
The deficiencies are as follows:
Information submitted to the Adacel license file (STN 125111/108) regarding the ----- assay to evaluate anti-pertussis toxin levels indicates that the assay conducted in your Canadian laboratory generates higher ----- values as compared to the values obtained in your U.S. laboratory. Preliminary information from your on-going investigation suggests that a pertussis toxin -------------------- from Canada contains some fimbrial antigen, resulting in higher anti-PT ----- values than those generated using a ------------------- which does not contain fimbriae. ----- values generated in your U.S. laboratory using the Canadian ------------------- appear similar to historical values generated in your Canadian laboratory using this ----------- --------------. The pertussis serology assays used in the Pentacel pivotal studies were conducted in your Canadian laboratory. Thus, these findings have potential implications for CBER's evaluation of the pertussis serology data submitted to the Pentacel BLA.
- Please submit available information from your on-going investigation to the Pentacel BLA.
- Please discuss the implications of these results for evaluation of the Pentacel serological data on pertussis. In this discussion please provide available information on the purity of the -------------------- used in the pertussis ----- assays conducted for the Pentacel pivotal studies and Study M5A07. Please provide the methods, standards used and acceptance criteria for assessment of purity of each -----------------------. Please provide the date these were established and any revisions that have been implemented since this time. Please provide qualification procedures and acceptance criteria for the ---------------------- (in addition to purity).
Based on our review of your responses to items a) and b) we may require submission of additional information and data. Please acknowledge.
We reserve comment on the proposed labeling until the application is otherwise acceptable.
Within 10 days after the date of this letter, you should take one of the following actions: (1) amend the application; (2) notify us of your intent to file an amendment; or (3) withdraw the application.
We stopped the review clock with the issuance of this letter. We will reset and start the review clock when we receive your complete response.
If you have any questions, please contact the Regulatory Project Manager, LCDR Edward Wolfgang, at (301) 827-3070.
/Paul Richman, Ph.D./
Paul Richman, Ph.D.
Division of Vaccines
and Related Products Applications
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research