FDA cites Boehringer Ingelheim plant in Germany

Just months after signing a consent decree for the manufacturing mess in its Ben Venue subsidiary, Boehringer Ingelheim finds itself on the firing line with the FDA again, this time for particle contamination in an API produced 4 and 5 years ago.

The German drugmaker has received an FDA warning letter, posted Tuesday to the FDA website, which takes it to task for not investigating the source of the particles found in batches of the active pharmaceutical ingredient which it made at a plant at Ingelheim am Rhein. The inspection took place last November and the issues stem from problems in 2008 and 2009, but inspectors did not let the company off the hook. It criticized the drugmaker for not investigating the source of the particles, some of them as large as 3 mm, and then even using the affected API to make finished capsules. The warning letter said it was not until last year that the company finally took "comprehensive corrections to mitigate the presence of foreign particles" in the API.

Additionally, inspectors pointed out that a batch of Boehringer's COPD product Spiriva HandiHaler had failed to give a uniform dose when tested at 9 months but that the company did not recall the lot until it again fell out of spec after 12 months. "We are concerned about the management decision to allow adulterated product to remain in the market between the 9 and 12 month stability stations," the letter said.

Wednesday, Boehringer Ingelheim said in a statement from the head of its quality division that the company was taking the warning letter issues very seriously. Dr. Gerhard Koeller said the company would "invest all our energy to remedy the situation." He pointed out that aside from the November FDA inspection, the plant had successfully passed 22 inspections by different authorities in the past 5 years.

Boehringer is already in it deep with the FDA. Its Ben Venue contract manufacturing operation in January signed a consent decree with the agency. The decree is tied to its Bedford, OH, plant, closed in 2011 after inspectors outlined a long list of serious manufacturing problems. Ben Venue issued 40 product recalls from 2002 until the plant voluntarily closed in November 2011. The closing, however, immediately led to shortages of important drugs such as Johnson & Johnson's ($JNJ) cancer drug Doxil, as well as drugs made by Pfizer ($PFE), Takeda and Bristol-Myers Squibb ($BMY).

As a result, the FDA found itself walking a fine line between between company accountability and drug accessibility when deciding what action to take. The decree bars the plant from manufacturing some drugs until the agency is satisfied that problems at the plant have been rectified. But the FDA is also allowing it to continue to manufacture 100 drugs considered "essential for patient care."

- here's the warning letter
- and Boehringer's response