Boehringer Ingelheim Receives 10-Observation 483

The FDA has handed Boehringer Ingelheim a 10-observation Form 483 for delays with a field alert report, as well as sanitation and sterilization procedures at a site in Germany.

The facility analyzed returned samples after some consumer complaints, and it determined on May 12, 2015, that a spray product did not meet dose specifications. Although it was required to file a field alert report within three working days, the facility waited until June 25, the FDA says.

The Feb. 29 to March 8 inspection found the plant did not test in-process materials for certain quality attributes to ensure they are consistent with final specifications.

Although the facility sterilizes drug product containers before aseptic filling, the investigators saw no process control measure to keep particulates out of certain containers.  They also noted failure to investigate the source of microbes in air samples or the dislocation of a ceiling panel.

In the microbe investigation, the company found bacteria during an environmental air monitoring investigation of an ISO 7 area, but it never determined its source.

Inspectors observed workers at the facility squatting and sitting near areas where aseptic filling was taking place.

One observation cited a number of issues related to air flow. Dynamic smoke studies of a filling area from 2011 showed that air could not properly flow from one zone to another, or flowed in the wrong direction. At the time of the inspection, Boehringer lacked verification that controls in these areas were corrected.

Inspectors noted the smoke studies fell short in some areas by not using enough smoke and failing to look at areas where there might be stagnant air.

A HEPA certification from last year in the facility’s ISO 5 filling area cited the potential for air turbulence due to a lack of uniform air velocity.

The 483 goes on to raise issues with some of the company's testing methods. For example, it did not validate a test method where opaque reservoirs of certain media are visually examined for microbial growth.

A separate validation failed to set operating ranges for process parameters related to water manufacturing. These could have included appropriate ranges for monitoring of flow/pressure for retention time. The company also did not regularly calibrate flow meters and pressure gauges that might be used in the monitoring process.

Boehringer Ingelheim told DID it responded to FDA’s observations within given deadlines and said it was confident that its corrective actions would address the agency’s concerns.

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