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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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6/29/2007 Fax

FACSIMILE TRANSMISSION RECORD

Division of Blood Applications
1401 Rockville Pike, Suite 400N, HFM-380
Rockville, Maryland 20852-1448

FAX (301) 827-2857
TEL (301) 827-3524

FAX No. 919-881-0014
To:   W. Gerald Coln, Carolina Research on behalf of Fresenius Kabi

Information Request: STN: BN070012/0

The review committee for this NDA application request Fresenius Kabi to respond to the following information request:

  1. General comment: The methods used should be United States Pharmacopeia (USP) compendial or fully validated. If the methods are European Pharmacopeia (EP) compendial, please provide the evidence that they comply with USP as well. For example, Validation report GM 0312.----------------------------------------------------------
    ----------------------------------------------------------------------------------------------------------------------------------------------------
    --------------------------------------------------

     

     

  2. Validation report: GM 0321. Please, indicate whether requirements for ------------- were defined (Table 2. Accuracy). Please, explain how the ------------------------ was determined.

     

     

  3. Validation report: GM 0332. The validation report states that GM 0332 has a ------------------------------------------------------------------------------; however, the report does not provide any quantitative data. Please, explain how many solutions/samples were used in this validation study (historical data can be provided). Are there any -------- data available to support a ------------------- testing?

     

     

  4. Validation report: GM 0359. Please, provide a rationale for using ------------------------------------------------------------------------------------.

     

     

  5. Validation report: GM 0379. Please, explain whether other validation parameters were considered in the GM 0379 validation study according to ------------------------------------------------------------------------------------------------------------------------------------------------------.

     

     

  6. ---------------------------------- (additional testing) of the HES 130/0.4 drug substance. Please provide information regarding --------------------------------------------------------------------------------------------------.

     

     

  7. Validation documents for validation that were not completed or submitted in the NDA:

     

    1. -------------------------------------------------------------------------------------------------------------------------------------------
      ---------------------------------------------------------
    2. -----------------------------------------------------------------------------------------------------------------------------
    3. ---------------------------------------------------------------------------------------------------------------------------------------
    4. ------------------------------------------------------------------------------------------------------------------------------
    5. --------------------------------------------------------------------------------------------------
    6. -----------------------------------------------------
    7. -------------------------------------------------------------------------------------------------------------------------------------------
      ----------------------------------
    8. -----------------------------------------------------------------------------------------------------
    9. -----------------------------------------------------------------------------------------------------------

     

  8. Please provide manufacturing dates for validation lots (84262, 84362, and 84572) for the HES 130/0.4 drug substance, and clarify any manufacturing changes implemented since validation lots were produced.

     

     

  9. When the manufacturing process was transferred from the Friedberg site to the Linz site, a comparison of the process was performed on batches produced. Please clarify when the transfer occurred in relation to the process validation and what batches were used for the comparison.

     

     

  10. For the ------------------- method, please confirm which method of analysis is actually used for the drug product. Please provide the validation report for the drug product with the method used for product release and ----------------------------------------------------------------.

     

     

  11. In the master file -------, section 2.3.S.2.4 controls of critical steps and intermediates, it was indicated that the -------------------------------------------------------------------------------------------------------------------------------------------
    ------------------------------------------------------------------------------------------------------------------------------------------
    -----------------------------------------------------------------------------------------.

     

     

  12. Please provide the rationale for the drug substance limit for ---------------------------------------------------------------------------------------------.

     

     

  13. Please provide the rationale for the --------------------------------------------------------------------------------------------------------.

     

     

  14. Please establish molecular weight distribution and number average molecular weight acceptance criteria for drug substance specifications, and stability testing parameters.

     

     

  15. According to the dataset named "input" you provided in the NDA submission, patients 53, 54 and 60 in study HS-13-14-NL received both the test product (6% HES 130/0.4) and the control product (6% HES 200/0.5). Please describe how these patients were handled in your analyses.

     

Please submit a response to this information request as an amendment to the file by COB 17-August 2007. If we do not receive the information by this date, a complete response letter will be issued that will contain the same items enumerated above.

If you need clarification please call me at 301-827-6165

Thanks,

Franklin T. Stephenson
Regulatory Project Manager
FDA/CBER/DBA/OBRR/RPMB


Information provided by: F. Stephenson     Date: June 29, 2007 2:45:01 PM

Approved by J. Kim   Date June 29, 2007   Transmitted by F. Stephenson   Date: 6/29/2007