FDA Warning Letter Calls for Action, Details Contamination of Alexion’s Drug, Soliris

A U.S. Food and Drug Administration (FDA) warning letter just sent to Alexion Pharmaceuticals, outlines potential contamination of its expensive, rare-disease medication, Soliris.

The warning letter followed the agency’s inspection of Alexion’s Rhode Island plant from July 12, 2012, through August 6, 2012. The FDA found, it said, “significant violations of current good manufacturing practices (CGMP) in the manufacture of licensed therapeutic drug substances” that caused its “active pharmaceutical ingredients”(APIs) “to be adulterated” under the Federal Food, Drug, and Cosmetic Act. The FDA added that it had “conducted a detailed review of your firm’s response and note that it lacks sufficient corrective actions.”

In March, Alexion sent out advance notice of the FDA’s warning letter that discussed “bacterial contamination of certain batches” of Soliris. In its letter, said FiercePharma Manufacturing, Alexion assured its investors that it is handling the matter; however, in a recent FDA posting, the agency stated that Alexion is experiencing difficulties locating the contamination source, thus, it is likely having problems fighting the contamination.

The biologic, Soliris, can cost up to $400,000 annually and is approved to treat atypical hemolytic uremic syndrome (HUS), a rare kidney disorder, and also paroxysmal nocturnal hemoglobinuria, a blood disorder, said FiercePharma Manufacturing. Last month, Alexion stated that it is avidly working on its issues and does not expect to experience Solaris supply interruptions.

Alexion stated that it is manufacturing Solaris and had stock of the drug in inventory. Also, in a filing with the Securities and Exchange Commission (SEC), Solaris indicated that Lonza, a contract manufacturer is on hand and approved to manufacture Solaris, said FiercePharma Manufacturing. Alexion also advised shareholders that it expects to secure a second contractor approved for Solaris manufacturing later in 2013. Despite this, Alexion did say that it plans on advising international regulators that “it is possible that the letter may impact our ability to supply Soliris manufactured at our Rhode Island facility outside the United States.”

Despite Alexion’s confident statements, the FDA said in its warning letter that, “It appears that you have not implemented a robust quality system at your firm,” noting that some of the CGMP violations were repeat offenses. The warning letter also stated that during its inspection, agency inspectors located six lots of APIs manufactured at its Rhode Island plant that, “were found to be contaminated with too numerous to count (TNTC)/10 mL Bacillus thuringiensis,” FiercePharma Manufacturing.

The letter went on to add that Acinetobacter radioresistens were identified in one lot of Soliris and, while Alexion fought the germ with more of a “sporicidal agent” in clean rooms, the drug maker never found or resolved the problem’s “root cause,” said agency inspectors, according to FiercePharma Marketing. The agency also said that Alexion neglected to confirm if using extra cleanser helped to eradicate the Acinetobacter radioresistens before production.

Inspectors also detected “residues in already-cleaned equipment” and noted that Alexion underwent “repeated bioreactor cleaning at least several times” over the course of one and a-half years, said FiercePharma Marketing. The FDA sought assurances from the drug maker that its cleaning cycle was “functioning appropriately.” Alexion stated that none of its finished product was contaminated, writing in an emailed statement that,” It is important to note that all of our released lots have met our rigorous release specifications, including testing for non-eculizumab protein and that these specifications have been approved by the FDA as well as other regulatory agencies. To emphasize, the final product is sterile.”

The FDA advised Alexion that it had 15 business days to advise the agency, in writing, about the steps it has taken to correct and prevent future violations and indicated that “failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction,” and noted that “other federal agencies may take this warning letter into account when considering the award of contracts” and the agency “may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until” the cited violations are corrected.” The complete letter is posted on the FDA’s website here.

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