The US FDA listed failure to ensure product sterility or explain why some batches were only partially released among criticisms of Apotex in a warning letter published this week.
In the letter - dated February 21 - the FDA said that Apotex failed to ensure sterility and perform airflow pattern studies for the filling line used to produce one of its injections at its plant in Toronto. The agency added that the company also failed to ensure its parenteral drug products were protected from contamination caused by the lack of unidirectional airflow.
In addition, Apotex released partial batches of product to the US market last year without specific criteria for the decision to not release other parts of the same batch or to describe “appropriate investigations.” Previous warning letters for Apotex have cited the same practice, the FDA said.
“Your firm’s practice of rejecting portions of drug product batches is an indication that your firm does not have well-controlled manufacturing processes,” Maan Abduldayem, FDA compliance officer, wrote in the letter from Feb. 21. “In addition, it raises concerns about the quality of the portions of those batches that you released.”
At another manufacturing facility in Ontario, Apotex was warned for not addressing all products that could have been affected by a sterility failure from last April that caused the company to reject batches of one of its injections.
The company was also cited for failing to record the incubation dates of the microbiological plates in the validation study of one of its solutions. Apotex initially said it “revised procedures, conducted a risk assessment, and will re-execute the validation” of the solutions, but the FDA said that is inadequate because it does not assess the impact of the company’s failure to document the incubation period on the released batches.
Similar violations were cited in warning letters in 2009 and 2010, according to the FDA. In 2011, Apotex’s shipments to the US were halted because of manufacturing violations cited in a FDA import alert. The alert was lifted in May 2011.
Steve Giuli, a spokesman for Apotex, told In-Pharmatechnologist.com that the company responded to the warning letter on March 13.
“We are actively working with the FDA to resolve the identified concerns as quickly as possible, and are optimistic that there will be a prompt resolution,” the company said in a statement. “In addition, we are actively working with Health Canada very closely to assure alignment with our local health authority’s expectations.”