Boehringer Ingelheim's manufacturing facility in Ingelheim, Germany has generated a lot of mail from the FDA. Last year it was a warning letter for deficiencies at the plant. In March it was a complete response letter denying approval for diabetes drug empagliflozin until the problems were fixed. Finally, some good news. Boehringer Ingelheim said today it received a letter from the FDA clearing the plant, meaning it and partner Eli Lilly ($LLY) can move forward with empagliflozin.
The company said in a statement today that the closeout of the warning letter was a "measure" of its progress on quality systems at the plant. More importantly, a spokeswoman said in an email that "Boehringer Ingelheim will resubmit the New Drug Application for empagliflozin, its investigational SGLT2 inhibitor, as soon as possible. The exact date for resubmission is currently being determined."
The May 2013 FDA warning letter stemmed from problems dating back to 2008 and 2009. The FDA criticized the facility for not properly investigating the appearance of particles contaminating batches of an active pharmaceutical ingredient it manufactured there. It said some of the particles were as large as 3 mm. Instead of getting to the root cause, the company used the contaminated API to manufacture finished capsules. The warning letter said it was not until 2012 that the company finally took "comprehensive corrections to mitigate the presence of foreign particles" in the API.
When it received the warning letter, the German drugmaker responded that it took it very seriously and pointed out that the plant had passed 22 inspections over 5 years. But the fallout became extremely serious when it resulted in the FDA holding up the approval of empagliflozin. That may have fallen hardest on Eli Lilly, which has promised it will capture "several" new drug approvals this year to make up for its dearth of approvals and flagging revenues. The rejection also came only weeks after Lilly's copycat version of Sanofi's ($SNY) market-dominant Lantus was put on hold by a lawsuit the French drugmaker filed claiming patent infringement. That may delay launch of Lilly's biosimilar until the middle of 2016.
The complete response letter has become a hammer that the FDA has used a number of times to get plant improvements from drugmakers. Last year, it held up approval of a migraine treatment from Allergan ($AGN) until it sorts out problems at an inhaler plant and also a treatment for symptoms of Parkinson's disease from Impax Pharmaceuticals ($IPXL) because of issues at a manufacturing facility.
- here's the announcement