Regulatory Focus™ > News Articles > Warning Letter to Alexion Pharmaceuticals Cites Repeat Violations, Bacterial Contamination

Warning Letter to Alexion Pharmaceuticals Cites Repeat Violations, Bacterial Contamination

Posted 09 April 2013 | By Alexander Gaffney, RAC

A new warning letter published by the US Food and Drug Administration (FDA) and sent to Rhode Island-based Alexion Pharmaceuticals, alleges the company's manufacturing practices are deficient and not in line with federal requirements, causing the active pharmaceutical ingredient it uses for the drug Soliris to be adulterated.


Alexion had alerted stockholders and the media to the existence of the warning letter several weeks ago. In an 8-K regulatory filing with the Securities and Exchange Commission, the publicly-traded company announced in late April that the Smithfield, RI facility had been cited by FDA regulators for current good manufacturing practice (CGMP) deficiencies.

Those deficiencies were related, it said, to "bacterial contamination of certain batches" and a "general concern that [Alexion had] not implemented a robust quality system."

The company has told investors that it has a backup plan to manufacture the Soliris API at another FDA-approved location, but that the Warning Letter "does not restrict production of Soliris or shipment of Soliris from the Rhode Island facility." A second backup facility is in the process of being validated, Alexion said at the time.

The Warning Letter

But until now, the details of the warning letter were sparse. FDA's 9 April 2013 release of that letter to the public provides new details, including those related to the bacterial contamination that was the cause of the majority of FDA's concern.

During the August 2012 inspection of the plant, FDA said that at least six lots of Soliris API were contaminated with Bacillus thuringiensis to the extent that investigators were unable to count the exact number of colonies, as they ordinarily do. Calling the contamination "too numerous to count," FDA said it was particularly concerned that Alexion "did not conduct an adequate assessment of the impact of this contamination on your final product, including the potential for non-host cell particle contamination, and you did not evaluate the ability of your manufacturing process to clear non-host cell impurities."

An additional lot was found to be contaminated with Acinetobacter redioresistens, FDA said. While Alexion had moved to introduce cleaning agents to decontaminate its clean room, the company never verified its effectiveness before resuming production of its Soliris API.

In another instance, two API lots of Soliris were found to have not met pre-specified limits for quality and safety, but were released by staff without "adequate scientific justification," FDA wrote.

FDA said that the sum total of the violations show that the company had failed to make necessary changes in the wake of prior inspections. "Several CGMP deficiencies that our investigators observed during this inspection were also observed during our inspection on 18 February 2011."

"We recommend that you implement a comprehensive quality system at your firm to encompass all manufacturing operations," FDA continued. "Repeat citations from prior inspections could indicate that your quality control unit is not exercising its responsibilities or may not have the appropriate authority to carry out its responsibilities." The company should hire an outside consultant to assist with this process, FDA added.

FDA said it "may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until the above violations are corrected," but did not say anything about ceasing production of the API.

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