Boehringer Ingelheim today responded to an earlier FDA warning letter faulting the company for not sufficiently investigating and correcting “significant violations” of current good manufacturing practice (cGMP) for active pharmaceutical ingredients (APIs) and finished pharmaceuticals found during an inspection last year at BI’s Rhine, Germany plant.
“Boehringer Ingelheim is taking this issue very seriously and is fully committed to working with the FDA on a comprehensive action plan that addresses the FDA’s concerns, ensuring that it implements corrective and preventive actions to optimize its quality systems,” Gerhard Koeller, Ph.D., BI’s head of corporate division quality, promised in a statement.
Dr. Koeller added: “We are committed to compliance with current Good Manufacturing Practices requirements. We will invest all our energy to remedy the situation in order to meet all FDA requests, building on the experience gained from all 22 inspections successfully passed at the Ingelheim site in the last five years by different authorities around the world, other than the latest FDA inspection in November.”
That inspection turned up instances of foreign particles in batches of APIs in 2008 and 2009, resulting in “adulterated” APIs and finished drug products in violation of cGMP, FDA said in its May 6 warning letter.
FDA chided BI for failing to thoroughly investigate critical deviations in API manufacturing to determine the source of the particles, and failing to implement “timely and appropriate corrective and preventive actions.” The company responded to a 2010 complaint about a contaminated batch manufactured a year earlier by declaring the complaint “not confirmed,” then ending the investigation without finding the contamination’s root cause.
A year later, however, BI closed another complaint by confirming that similar contamination in one drum of an API lot was manufacturing-related.
BI was also faulted for failing to reject multiple batches of capsules contaminated with foreign particles in 2010 and last year. FDA said the company failed to determine the cause of the “out-of-specification” finding for a lot of once-daily COPD treatment Spiriva HandiHaler that failed a uniformity-of-delivered-dose test specification within the required nine-month stability interval.