Regulatory Focus™ > News Articles > US Regulators Revoke Unique Exemption from Compounder in Wake of Concerns

US Regulators Revoke Unique Exemption from Compounder in Wake of Concerns

Posted 08 February 2013 | By Alexander Gaffney, RAC

US Food and Drug Administration (FDA) officials have sent to a letter to one of the country's largest pharmaceutical compounders, reprimanding it for what they say are deviations from the terms of an agreed-upon plan that allowed it to operate more like a manufacturer, but with special conditions.


The manufacturer, Illinois-based PharMEDium, had established a program with FDA in 2005 that allowed the company to compound drugs wholesale, and later on link those products to consumers with valid prescriptions.

Under current law, compounders are allowed to manufacture products for consumers, but are ordinarily required to compound the drug for that specific person, and only after they receive a valid prescription. FDA has, in a number of cases, issued warnings to compounders for having supplies of already-compounded drugs stocked in their facilities awaiting receipt of a prescription.

But PharMEDium was able to circumvent this after convincing FDA that a barcode-based system would allow it to link its compounded drugs to specific patients with a sufficient degree of sameness to the current system. FDA's letter to PharMEDium notes that it had "expressed willingness to exercise enforcement discretion on the patient specificity issue at that time," but that it was already intended to be a temporary, if ongoing, agreement.

That impermanence was known to PharMedium as well, and in January 2013 it sent a letter to FDA's Heidi Marchand, assistant commissioner for FDA's Office of Special Health Issues, in which it asked for FDA to reaffirm its compounding approach as acceptable.

But if the company was hoping for good news in the form of a reaffirmation, it received just the opposite. "FDA is no longer willing to condition our exercise of enforcement discretion in the manner set forth in the 2005 letter," Janet Woodcock, director of FDA's Center for Drug Evaluation and Research (CDER), wrote in her 5 February 2013 response to the company.

The problem, FDA said, is twofold: The company has specific deficiencies related to its unique compounding program, and FDA has concerns related to compounding in general following recent events.

Compounding Problems: Specific and General Concerns

PharMEDium, FDA wrote, had failed to consistently implement or maintain the conditions stipulated in the 2005 agreement. Specifically, the company had failed to proactively determine whether each of its drugs was being dispensed to the proper patient. A 2007 inspection of the company's Sugarland, TX facility allegedly found that its management claimed it was the prescribing hospital's duty to ensure appropriate dispensing.

That lack of linkage was troubling, FDA explained, particularly in light of reports that multiple infections of Sphingomonas paucimobilis had been associated with a fentanyl IV product manufactured by PharMEDium. Those hospitals with infected patients were unable to determine which lots of fentanyl the patients had received, FDA said.

Given the lack of traceability in that case and others-what regulators repeatedly referred to as a "specific linkage"-FDA said it would no longer exempt the program.

Its confidence in the program was also shaken by a recent outbreak of fungal meningitis which has killed dozens and injured hundreds more across the US. That meningitis has been spread through compounded products manufactured by the New England Compounding Center. Regulatory authorities have since been scrambling to contain that outbreak and to assess other compounding facilities for similar weaknesses.

Because PharMEDium, like NECC, was compounding products at a large scale, FDA said it was concerned that compliance standards for large-scale sterile production may not have been met, putting other patients at similar risk for harms.

"We have determined that, going forward, we are no longer willing to accept, as a matter of enforcement discretion, the approach outlined in the pilot study as a means of satisfying the requirement for a valid patient-specific prescription," FDA explained, adding that it believes "new legislation is needed."

Several large-scale pharmaceutical facilities, such as a Danish plant owned by Novo Nordisk and Boehringer-Ingelheim's Ben Venue facility have been struck by similar sterility concerns in recent months, likely adding to FDA's concerns about smaller facilities' ability to keep to sterile manufacturing practices.

Other Troubles for PharMEDium

The release of the letter comes just as PharMEDium was also part of a lengthy investigative piece by the Washington Post that illustrates the uneven record of the compounding industry and FDA's efforts to enforce it.

The same report took particular note of PharMEDium, explaining that its products were associated with a number of errors, including mislabeled products that were accidently administered to patients and contaminated products.

FDA defended its regulatory record elsewhere in the piece, noting-as is regularly does-that the agency is operating in a fractured legal and regulatory environment in which it has questionable and inconsistent authority.

"You are seeing a bunch of people trying to do their best in a system that is legally and factually complicated," said Howard Sklamberg, director of compliance for CDER to the Post.

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