Inspections of the facility in September 2010 identified shortcomings in contamination-prevention procedures. Sanofi responded in October 2010 and January 2011 but the US Food and Drug Administration still has concerns and on February 9 sent a warning letter to the German facility.
Failure to establish or follow “appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile” is the first issue raised in the warning letter.
Sterility testing of Apidra (insulin glulisine), a single lot of which was voluntarily recalled in 2010, is the focus of some of these concerns. In June Sanofi failed to identify the organisms recovered from a sterility test for Apidra lot #OF100, according to the FDA.
Failure to identify organisms recovered from a sterility test was also discussed during a December 2008 FDA inspection. Identification of organisms is “a fundamental part of any investigation of environmental or personnel monitoring excursions”, says the FDA.
Sanofi said it "has moved quickly to address issues raised" by the FDA and expects to fully address the agency’s concerns “in a timely manner”.
Failure to establish “separate or defined areas or such other control systems as necessary to prevent contamination or mix-ups during aseptic processing” is another issue in the warning letter.
Examples of this include unacceptable airflow velocity in critical aseptic processing areas and lack of assurance that environmental contaminants are reliably detected. The FDA says collecting samples from operators’ left and right gloves on alternate days is unacceptable.
Finally, the FDA says: “[Sanofi] failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions.”
Adverse event reporting
Sanofi received another FDA warning letter, dated January 28, for failing to comply with postmarketing adverse event reporting requirements. Since receiving a 483 in May 2010 Sanofi has sent three responses to the FDA but the agency believes corrective actions are inadequate.
“Failure to review, evaluate, and submit adverse drug experience (ADE) reports that are both serious and unexpected to FDA within 15 calendar days of initial receipt of the information",is one of the FDA concerns.