Inspectors visited the Grand Island, New York manufacturing plant in June but some of the concerns predate this time. In January 2010 APP found an insect floating in a waste container housed in an aseptic filling room. Others were found in the production area and inside a vial APP distributed.
“You did not adequately investigate the original deviation for an insect in the sterile manufacturing area and did not implement appropriate corrective actions to prevent recurrence”, the FDA wrote in its warning letter.
An insect was last found in March 2011 but the FDA wants APP to monitor its corrective actions to stop the problem reoccurring. In a statement responding to the letter, Fresenius Kabi, the owner of APP, said it ‘has made significant progress in collaboration with the FDA in remedying these issues’.
Other problems APP must address include failure to find the cause of out of specification results for batches of heparin API (active pharmaceutical ingredient) and heparin lock flush. APP must show the FDA a three-year history of similar results, the cause, and the investigation conclusion.
Handling complaints
The APP warning letter is the latest in a string of FDA regulatory actions to criticise the handling of complaints by biopharma companies. APP failed to follow rules for handling written and oral complaints, the FDA wrote, and inspectors linked this to several deficiencies at the production site.
“You received [a] complaint citing dark particulate matter in a vial of heparin. You investigated and determined that the particle was most likely due to a vendor issue; however, you did not perform an assessment of the vial supplier”, the FDA wrote.
The FDA sent the warning letter on February 22. A day earlier Mitchell Ehrlich, vice president of quality assurance at APP, sat with the FDA at its drug shortages press conference and said “in-house manufacturing is a more reliable way to supply the market than a virtual supply chain”.