In an apparent first for a generic drug company with an excellent manufacturing record, FDA has served Mylan NV with a warning letter for cGMP failures at its Caguas, Puerto Rico finished pharmaceuticals manufacturing plant.

The company failed to complete the content uniformity test required by the United States Pharmacopeia after a lot of loperamide capsules (generic Imodium) failed to conform to acceptance criteria, FDA found in an inspection conducted Jan. 24 to Feb. 24. This amounted to a lack of "appropriate laboratory determination of satisfactory conformance to final specifications for the drug product prior to release" for the given batch, FDA said.

Moreover, in the company's March 14 response to FDA, it "failed to include the scientific rationale (e.g., statistical justification) for not completing the CU test," according to the Oct. 13 warning letter, which FDA posted to its website Nov. 22.

FDA also said Mylan had fallen down on investigating batch failures. The company attributed certain out-of-specification results to "assignable causes" (although what exactly those were FDA redacted from the version of the warning letter it posted online), "but failed to include sufficient supporting evidence to invalidate the initial data." The March 14 response also did not include a scientific rationale for this, the agency said.

Standing Up For Reputation

"We intend to work closely with FDA to fully address the observations in the agency’s letter and believe we will be able to resolve this matter expeditiously," the company said in a statement.

"Production and shipment of product from the Caguas facility continues uninterrupted. Mylan has an unwavering commitment to quality everywhere we operate, and we have the highest respect for FDA, its mission and processes, and fully support the agency's efforts around the world."

The company refused to comment on what other products might be impacted by problems at the plant, but FDA has suggested that one of Mylan’s higher profile products, the generic version of Pfizer Inc.’s Lipitor (atorvastatin), could have application problems. Mylan’s efforts to break Ranbaxy Laboratories Ltd.'s generic exclusivity for the blockbuster statin have been turned away by the courts in part because FDA indicated that Mylan’s ANDA was not ready for approval Also see "Lipitor Generics: Questions About Mylan's ANDA Weigh Heavily In Court's Dismissal Of Lawsuit Against FDA" - Pink Sheet, 3 May, 2011..

Mylan has been known to aggressively defend its manufacturing quality reputation. In August 2009 the company filed a civil suit in the Circuit Court of Monongalia County, W.Va., against the Pittsburgh Post-Gazette, alleging that the newspaper improperly obtained and misconstrued confidential internal documents in a series of articles about its West Virginia generic plant Also see "Legal News In Brief" - Pink Sheet, 24 August, 2009..

That reputation does appear to be clean, at least from FDA's point of view. The only other enforcement letter Mylan appears to have received from FDA in recent years was in 2003, when the agency cited it in a "notice of violation" letter for claims on a website for its acne drug Amesteem (isotretinoin) that the product could address problems with low self-esteem Also see "Amnesteem Cannot Claim “Esteem,” FDA Tells Mylan In Letter On Acne Drug" - Pink Sheet, 30 June, 2003..

More recently, the company has led a high-profile effort to build congressional support for generic user fees to finance inspections of overseas drug manufacturing facilities on the grounds that foreign firms undergoing less FDA scrutiny had an unfair advantage Also see "Establishment Fees Protect American Manufacturing, Mylan Argues In User Fee Proposal" - Pink Sheet, 20 December, 2010.. The point seems to have been underscored in an ironic way by FDA's enforcement action against Mylan.

Mylan Gets First-Ever GMP Warning Letter

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