Boehringer Ingelheim handed FDA warning letter

Boehringer Ingelheim, whose contract manufacturing facility in Bedford, OH, has been at the heart of huge drug disruptions in the U.S., is now feeling the sting of FDA inspectors at a key plant in Europe.

The German drugmaker has received an FDA warning letter, posted yesterday to the FDA website, which takes it to task for not investigating the source of large particles in batches of an active pharmaceutical ingredient manufactured at a plant at Ingelheim am Rhein. Most companies only discuss warning letters when directly asked, but Boehringer Ingelheim took the proactive approach. It put out a statement today from the head of its quality division saying the company was taking the warning letter issues very seriously. Dr. Gerhard Koeller, head of Corporate Division Quality, 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.

The inspection was in November 2012 and the issues stem from problems in 2008 and 2009, but inspectors did not let the company off the hook for not investigating the source of the contamination and then using the affected API to make finished capsules. It said some of the particles were 3 mm in size, or about one-eighth of an inch. The letter redacted what the particles were determined to be. The 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.

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