US FDA Rebukes Alexion APIs, Pfizer Italian Subsidiary in Warning Letters

In Alexion’s production of its rare blood and kidney disorder drug Soliris, six lots of the API for the drug were found to be contaminated with the bacteria Bacillus thuringiensis ​and the microorganism Acinetobacter radioresistens.​ 

The underlying root cause of the contamination was not identified and the company failed to adequately assess the impact of these contaminants or “the ability of your manufacturing process to clear non-host cell impurities​,” according to the US Food and Drug Administration (FDA).

The inspection from last July and August also found that the Smithfield, Rhode Island-based facility had “residues in already-cleaned equipment​.” Furthermore, the FDA found Alexion has not implemented a “robust quality system​” as some of the deficiencies were repeats from an earlier inspection in February 2011.

“Due to continuing CGMP issues at your firm, we recommend you engage a third party consultant with appropriate CGMP expertise​,” Mutahar Shamsi, the FDA’s district director in the New England district office wrote.

The site was initially approved by the FDA in 2010​ as a second location where Soliris could be manufactured to avoid shortages of the drug. Alexion did not respond to a request for comment before press time.

Wyeth Lederle​

In addition to the warning letter for Alexion, the FDA also released yesterday its warning letter for Catania, Italy-based Pfizer subsidiary Wyeth Lederle S.p.A.

The July 2012 inspection of the facility found the company failed to explain how out-of-specification (OOS) endotoxin results were the result of interference for a batch of Torisel, part of which was sent to the US for distribution in January 2012.

Although the company performed extensive repeat testing of the Torisel batch, the tests ended with “inconsistent passing and failing results​.” And the company failed to “conduct quantitative endotoxin testing to determine the extent of the endotoxin specification failure​.”

The FDA calls for “an updated manufacturing investigation outlining potential sources for endotoxin contamination in the lot, and your proposed preventive actions​.”

The company also failed to issue a "Field Alert Report" for the contaminated batch sent to the US until more than eight months after it had been released and four months after discovering the contamination. The reports are supposed to be sent within three working days of receipt of information concerning any bacteriological contamination, the FDA said.