FDA warning cites Hikma plant for repeatedly failing to investigate issues

Hikma recently acknowledged that it had received a warning letter from the FDA for a plant in Portugal. The drugmaker said the FDA was concerned about how the facility had handled investigations and environmental monitoring at the sterile drug facility. What the drugmaker did not disclose is that some of the warnings were repeats, noted in three previous inspections of the facility dating back a decade.

According to the warning letter, posted today by the FDA, the plant in Fervenca, Terrugen, Portugal, has not gotten to the root cause of nearly two dozen instances in which environmental monitoring samples exceeded action levels in the Class 100 aseptic area on one of its filling lines. There was no proof that the outliers were "false positives" as the company indicated, FDA inspectors said. And Hikma didn't bother to check further to see if products had been compromised as a result.

The FDA was also concerned about the fact that by incubating media plates ahead of their use, it might be impeding the media's growth-promotion potential, leaving open the possibility that the plant is not getting accurate readings and so cannot be absolutely sure its injectable drugs are sterile. The letter said that Hikma has been warned about its lack of investigations after inspections in 2004, 2007 and 2011.

Further, the FDA chastised the company for the way it was training employees to do visual inspections for particulate. It noted that the vials used for testing were marked on the stoppers with "a number or a dot that was easily visible to the operator who was holding the vial during qualification," so it was obvious which vials were supposed to be rejected. That suggests the company can't be sure that products with particulate weren't getting through. Hikma had been warned in the 2011 inspection that its practices for monitoring for particulates in its sterile drugs were insufficient and said it needed to submit an action plan.

When Hikma acknowledged the warning letter in an announcement last month, it said, "Hikma takes this matter very seriously and will work with the FDA to fully resolve all outstanding issues."

But in its warning, the FDA said the fact that problems have persisted at the plant indicates Hikma has not put together a global corrective program to ensure quality manufacturing at all of its facilities. The drugmaker has 27 plants around the world and has been expanding its sterile manufacturing. Last year, the drugmaker earned $536 million, or nearly 40% of its revenues, from injectables, with sales in the U.S. accounting for 68% of that. It recently agreed to pay up to $300 million to buy the generic injectable drugs that Germany's Boehringer Ingelheim sold under its Bedford Laboratories brand.

- here's the warning letter