Vaccines, Blood & Biologics

Cangene Corporation Untitled Letter


July 21, 2010

John Langstaff, Ph.D.
President and CEO
Cangene Corporation
155 Innovation Drive
Winnipeg, Manitoba
Canada R3T5Y3

Dear Dr. Langstaff:

The Food and Drug Administration (FDA) conducted an inspection of Cangene Corporation, located at 155 Innovation Drive, Winnipeg, Manitoba, Canada, from April 12 to 22, 2010. During the inspection, FDA investigators documented deviations from current good manufacturing practice (CGMP) requirements in the manufacture of licensed biological products and bulk drug substances. These products include WinRho® SDF, HepaGam B™, and Vaccinia Immune Globulin Intravenous (Human). These deviations from CGMP include the applicable requirements of Section 501(a)(2)(B) of the Federal Food, Drug and Cosmetic Act (FD&C Act), Section 351(a) of the Public Health Service Act (PHS Act), and Title 21, Code of Federal Regulations (21 CFR) Parts 210, 211, and 600-680. At the close of the inspection, FDA issued a Form FDA 483, Inspectional Observations that described a number of objectionable conditions relating to your facility’s compliance with CGMP. Significant deviations observed during the inspection include, but were not limited to, the following:

  1. You failed to thoroughly investigate any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications; failed to extend investigation to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy; and failed to assure that written records of investigations were made and include conclusions and follow-up [21 CFR 211.192]. For example:
    1. The investigation into the reason non-conforming component vial lot ---(b)(4)--- was released is inadequate. Your investigation identified --(b)(4)-- residue and/or water marks as potential root causes for the unknown white substance/coating. These could not be ruled out due to lack of documentation. Additionally, prior to completion of the investigation WinRho Liquid Lot ---(b)(4)--- and HepaGam B Lots ---(b)(4)--- and ---(b)(4)--- filled with non-conforming component vials from vial lot ---(b)(4)--- that were coated with the unknown white substance/coating, were wiped clean and released.
    2. The impact assessment for the investigation of non-conforming component vial lot --(b)(4)-- was made without testing any vials and determined there was no impact on product quality for HepaGam B Lot ----(b)(4)----. Furthermore, the investigation was closed and did not extend to other lots filled with vials from vial lot ---(b)(4)---.
  2. You failed to follow appropriate written procedures to prevent microbial contamination of drug products purporting to be sterile [21 CFR 211.113(b)]. For example, there are no validation data to support the efficacy of viable air particle sampling during filling operations utilizing -----------------------------------------(b)(4)----------------------------------------- device.
  3. You failed to establish laboratory records including complete data derived from all tests necessary to assure compliance with established specifications and standards, including the suitability of all testing methods used and verified under actual conditions of use [21 CFR 211.194(a)(2)]. For example, the -------------------------(b)(4)-------------------------- test for precision is not performed in the following quantitative analytical methods “-------------------------------------------------- (b)(4) --------------------------------------------------,” and “-----------------------------(b)(4)------------------------------” to assure that the test methods are suitable for the intended applications.

Additionally, deviations in manufacture of your bulk drug substances were observed during the inspection. These deviations violate Section 501(a)(2)(B) of the FD&C Act and Section 351(a) of the PHS Act. Specific areas of concern include, but are not limited to:

Laboratory Controls

  1. You failed to provide data to establish that the methods used in testing meet proper standards of accuracy, reliability, and suitability. For example:
    1. The ---(b)(4)--- method used to determine in-process bioburden (-------------------------------(b)(4)--------------------------------) does not consistently demonstrate that bioburden can be adequately recovered in that the method does not ensure that inhibition from the product does not interfere with recovery of microorganisms.
    2. The -----------------------(b)(4)------------------------ test for precision is not performed for the analytical method “-----------------------------------------------(b)(4)-----------------------------------------------” to assure the test method is suitable for the intended application.
  2. The bioburden sampling size of (b)(4) is not representative of the volume in determining ---(b)(4)--- bioburden levels.

We acknowledge receipt of your written responses dated May 13 and June 22, 2010, which address the inspectional observations on the Form FDA 483 issued at the close of the inspection. We also acknowledge your many commitments and improvements, including the establishment of a dedicated “Quality System Improvement Department”; the implementation of deviation management process improvements; and increased leadership in the Quality function.

Neither the above deviations, nor the observations listed on the Form FDA 483 presented to your firm at the conclusion of the inspection, are intended to be an all-inclusive list of deviations at your establishment. It is your responsibility to ensure compliance with all requirements of the laws and regulations administered by FDA.

Your reply should be sent to me at the following address: U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Suite 200N, Rockville, Maryland 20852-1448. If you have any questions regarding this letter, please contact Mary D. Davis-Lopez in the Division of Case management at (301) 827-6201.



Mary A. Malarkey
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research

cc: Andrew Storey
Vice President
Quality, Clinical & Regulatory Affairs
Cangene Corporation
155 Innovation Drive
Wininipeg, MB R3T 5Y3

Minerva Dever
Authorized U.S. Agent
Cangene Biopharma, Inc.
1111 South Paca Street
Baltimore, MD 21230-2591

Page Last Updated: 07/29/2010
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