Expanded FluMist Indication Delayed by cGMP Violations

The FDA issued MedImmune, Inc. (Gaithersburg, MD, www.medimmune.com), a warning letter for violating the agency’s manufacturing rules and held off approving the company’s influenza vaccine for use in children younger than age five until the problems are resolved. FluMist, an intranasal vaccine, is currently approved for use in people ages five to 49 years old.

MedImmune received a warning letter from the FDA on May 24, 2007, citing significant deviations from current good manufacturing practice (cGMP) in the manufacture of FluMist bulk monovalent lots used to formulate the vaccine.

The letter describes the results of a March 2007 FDA annual inspection of MedImmune’s plant in the UK where it makes bulk material for FluMist. At the close of the inspection, FDA issued a Form FDA 483, Inspectional Observations, which described a number of significant deviations in the manufacture of the bulk monovalent lots. Specific areas of concern included:

• The investigations that the firm performed for the interim bioburden action limit were not performed in accordance with cGMP because they were inadequate, and because corrective and preventive actions were neither identified nor implemented to prevent recurrence.

• Failure to ensure that operators performing setup, sterile filtration, and aseptic dispensing use proper aseptic techniques to prevent microbial contamination of monovalent lots.

• Master and batch production records lacked specificity. This issue was discussed with senior management at the firm during the March 6 to March 9, 2006, inspection and correction was promised, but had not been achieved.

• Failure to establish the effectiveness of the cleaning and disinfection processes used in the manufacturing facility and by the personnel.

• Failure to establish separate or defined areas or other control systems for the operations to prevent contamination or mix-ups.

• Cleaning validation for the [redacted] incubators, the dispensing and biological safety cabinets, and the silicon rubber housing of the candling lamps had not been performed.

The letter instructed MedImmune to take prompt action to correct these deviations and said that the failure to promptly correct these deviations could result in FDA initiating regulatory action that could include license suspension or revocation.

According to MedImmune, the company was working with FDA to resolve problems at the manufacturing plant and to be able to release FluMist for the upcoming 2007–2008 influenza season on time.