On the API side, the FDA inspectors cited Boehringer’s quality unit for failing to thoroughly investigate deviations in manufactured APIs from 2008 and 2009, according to the warning letter from the agency’s November 2012 inspection. The company failed to determine the source of the foreign particles and continued to use lots of APIs that were identified as contaminated with the particles.
The German site is one of nine facilities the company uses for manufacturing worldwide.
“We are concerned about your inability to prevent the presence of foreign particles in your APIs and the adequacy of actions taken to address the situation,” Rafael Arroyo, FDA Compliance Officer said in his letter to Dr. Gerhard Gigl, senior vice president of Boehringer-Ingelheim.
For its finished products, the FDA also criticized the company for releasing capsules in which foreign particles as large as about 5 mm and weighing about 9 mg – roughly the size of a marble – were found. The agency also said it disagreed with the company’s decision to allow the use of these drugs even though the contaminated batches met final specifications.
“Quality cannot be added into a product after it has been manufactured,” the FDA said.
In addition, the company failed to determine the cause of an out of specification lot of its Spiriva HandiHaler, which “failed the uniformity of delivered dose test specification,” according to the agency.
Previous Issues
Just prior to the FDA’s inspection of the Ingelheim, Germany facility, the company announced it would invest more than $100M in its other German manufacturing site in Dortmund. That initiative came as part of a plan to create more of the company’s Respimat inhalers, which are the delivery devices for Spiriva.
Boehringer’s US subsidiary Ben Venue Laboratories had a long history of quality issues and was hit with a consent decree in February, though the Ohio facility continued limited manufacturing.
The company did not respond to a request for comment by press time.