Warning Letter: Sanofi Pasteur

Vaccine maker Sanofi Pasteur, Inc. (Swiftwater, PA,  www.sanofipasteur.com)received a US Food and Drug Administration Warning Letter (http://www.fda.gov/foi/warning_letters/g5899d.html),dated June 30, citing "significant deviations" from current goodmanufacturing practices (CGMPs) in the production of monovalentconcentrates used in the company's "Fluzone" influenza vaccine.

In late March, Sanofi Pasteur reported to FDA that some of themonovalent concentrates had failed sterility testing. The source of thecontamination has not been determined nor thoroughly correctly, whichprompted FDA to issue the warning.

The cited deviations included:

• On the Fluzone production floor, equipment and supplies exposedto "any potentially pathogenic agent" were not adequately separatedfrom product manufacturing equipment and supplies to preventcross-contamination (21 CFR600.11[e][5]).

• The company failed to establish a system for maintainingequipment to control aseptic conditions, to follow written proceduresto prevent microbial contamination of sterile drug, and to ensure thaterrors are investigated (21 CFR211.42[c][10][vi]), 211.113[b], and 211.22[a]).  

• Appropriate written procedures to prevent microbial contaminationof sterile drug products were not followed (21 CFR 211.113[b]).  

• The company did not establish that test methods used at the siteare accurate, sensitive, specific, and reproducible (21 CFR 211.165[e]).  

• No event and relevant information associated with themanufacturing of a licensed biological product that deviated fromCGMPs, regulations, standards, or specifications that may affect thesafety, purity, or potency of a distributed biological product werereported to FDA (21 CFR 600.14[b]). 

• The company did not inform FDA's Center for Biologics Evaluationabout a change to its licensed product-stability testing program (21 CFR 601.12[a]).  

In addition, the warning letter cited deviations in the manufacture ofthe monovalent concentrate used to formulate Fluzone that violateSection 501(a)(2)(B) of the FD&C Act and Section 351(a) of the PHSAct.

According to the letter, the deficiencies "are indicative of yourquality control unit not fulfilling its responsibility to assure theidentity, strength, quality, and purity of your drug product [21 CFR 211.22] . . . Failure topromptly correct these deviations may result in FDA initiatingregulatory action without further notice.  Such action may includelicense suspension and/or revocation, seizure, and/or injunction."

The plant can continue to make the vaccine, and according to FDA, thedeficiencies should not affect its availability for the 2006-2007 fluseason.