COMMENT
The FDA published last Wednesday (July 25, 2012) a multipage Warning Letter to Sanofi Pasteur’s facilities in Toronto, Canada and Marcy l’Etoile, France. This Warning letter followed extensive GMP audits of both facilities between March 19 – April 2, 2012 (France) and April 10 and April 25, 2012 (Canada). Within the Warning Letter are issues relating to the manufacture of vaccines produced at each site. The FDA notes that the Warning Letter describes “significant objectionable conditions relating to each facility’s compliance with CGMP”.
The Warning Letter issued to Sanofi Pasteur represents a significant situation as noted by both Sanofi Pasteur and the FDA. The Toronto facility has chosen to voluntarily suspend selected operations within their Toronto facility. Please view below the initial Observation from the Warning Letter as well as the follow-up from both Sanofi Pasteur and the FDA.
1. You failed to establish the accuracy, sensitivity, specificity, and reproducibility of test methods employed by your firm [21 CFR 211.165(e)]. Sterility for all lots of TheraCys®, BCG Live (Intravesical) (BCG-IT) manufactured in Building (b)(4) since the last successful BCG Sterility Test Method Validation in 2000 cannot be assured. Revalidation of the BCG Sterility Test Method conducted from March through April 2012 failed acceptance criteria for bacteriostasis/fungistasis testing; there is no assurance that the test method is capable of detecting yeast and/or mold in the product. Further, there have been no less than 58 documented non-conformances relating to the isolation of mold within the BCG aseptic processing areas (Grade (b)(4) (b)(4) areas) of Building (b)(4) since August 2010.
Sanofi Pasteur and FDA’s Response to Form FDA 483 Observation 1
We acknowledge receipt of your June 21, 2012, correspondence advising FDA that Sanofi Pasteur has decided to temporarily suspend manufacturing of TheraCys® (Intravesical) (BCG-IT). Your correspondence states that manufacturing has been suspended in order to renovate the Toronto BCG manufacturing facility (Building (b)(4)) to improve the quality of the environment within this production building. Your correspondence further states that Sanofi Pasteur is working to resolve issues encountered during recent sterility method revalidation studies in order to establish a fully validated sterility test applicable to BCG-IT
The FDA has also indicated that “To facilitate your remediation efforts, we request a meeting with you (Olivier Charmeil, Senior Vice President, Vaccines) and other senior management at Sanofi to further discuss the issues cited in this letter and your proposed responses to address them.”
The entire Warning Letter may be viewed at: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm312962.htm
COMMENT
Additional Blogs will also be forthcoming on this significant Warning Letter. This Warning Letter represents another “shot across the bow” to industry and the consequences of not following 21 CFR 210, 211 and 600 – 680.
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