The inspections began Feb. 19 and will continue over the next two months, covering about 30 facilities. Depending on the findings, the specialty pharmacies, known as compounders, could face fines and possible suspension of their licenses. These pharmacies custom-mix medications for individual patients, hospitals and clinics.
The actions are part of a new program aimed at the multibillion-dollar compounding industry that has fallen between the regulatory cracks. The inspections were the first targeted enforcement actions against large compounders since the FDA found filthy conditions at a Massachusetts pharmacy that shipped contaminated steroid shots to 23 states. The shots caused the outbreak that has so far killed 48 people and sickened 666 others, making it the country’s worst drug disaster in several decades.
Those already inspected include two companies identified in a Washington Post investigation in February about manufacturing-style compounding pharmacies.
The Post investigation found that shoddy practices and unsanitary conditions at three large compounding pharmacies have been tied to deaths and illnesses over the past decade. The findings showed that serious safety lapses at the Massachusetts-based New England Compounding Center were not an isolated occurrence.
The Post also reported that state and federal authorities did little to systematically inspect and correct hazards at compounding firms. In the lightly regulated industry, pharmacies were rarely punished, even when their mistakes had lethal consequences.
Howard Sklamberg, director of compliance for the FDA’s Center for Drug Evaluation and Research, said in an interview Friday that inspectors focused on the firms that compound sterile injectable products — such as the steroids that triggered the meningitis outbreak last October.
Inspectors also went into facilities that had a history of problems linked to patient illnesses and deaths.
“Because we have limited resources, we have to target firms that pose the greatest risk,” Sklamberg said.
FDA reports show that inspectors found 39 safety deficiencies at the four firms. Two of the firms are among the largest compounding companies in the nation — and were the major focus of the Post investigation.
At California-based Central Admixture Pharmacy Services’ facility in Illinois, inspectors found that personnel failed to take adequate steps to “prevent microbial contamination of drug products.” In one storage room, a bag of citric acid had a hole, which exposed it to possible contamination. Inspectors also found that personnel had failed to properly investigate leaks in a sterile nutritional supplement and potency problems with another drug.
At Illinois-based PharMEDium Services, inspectors found the company’s Cleveland, Miss., facility did not have an appropriate air filtration system, critical to keeping contaminants out of drugs. They also found “rust colored build up” behind a special filter that removes contaminants from the air, and quarter-inch holes in walls by an area where drugs are mixed.
Mike Koch, a vice president at CAPS, did not provide a direct response to the FDA findings. However, he said the company “fully cooperates with the FDA to ensure patient safety and continuous improvement.”
A PharMEDium spokesman said company policy is not to comment on inspections. But spokesman Bob Szafranski added that the FDA inspects the company facilities on a routine basis and “we welcome their oversight.”
An FDA spokeswoman said, however, that inspectors have not conducted routine inspections because they generally investigate these facilities only when they are alerted to complaints, such as contaminated products or patient illness or death.
The two other firms inspected were AnazaoHealth in Florida and Lee Pharmacy in Arkansas. At AnazaoHealth, FDA inspectors said the company did not have manufacturing procedures in place to prevent contamination of its drug products and that drug product containers were not clean and sterilized.
In a statement to the Post, AnazaoHealth’s Corporate Counsel said that compounding pharmacies fall under the authority of states’ boards of pharmacy, not the FDA, and that inspectors from the Florida Drugs, Device and Cosmetics program were also at the facility during the inspection and found no deficiencies.
At Lee Pharmacy, inspectors found the facility lacked the proper procedures and programs to ensure that drugs have the “strength, quality, and purity they purport or are represented to possess.”
In response, Lee Pharmacy owner Warren Lee said, “I don’t agree with a lot of it.” He declined to elaborate.
The enforcement effort is presenting several challenges, Sklamberg said.
Unlike drug manufacturers, which make FDA-approved products, the pharmacies do not have to register with the agency or tell them what medications they produce. As a result, Sklamberg said, inspectors do not know exactly what they will encounter when they arrive at the facilities.
“A lot of these firms are behaving like drug manufacturers and producing like drug manufacturers, yet they are trying to operate under the law as if they were a small pharmacy,” he said. “They are trying to put the square peg in a round hole.”
The FDA is seeking authority from Congress to require registration, which would allow the agency to demand that firms release detailed information about operations and give it greater authority to require safety problems be fixed.
Sklamberg said the FDA coordinated with state boards of pharmacy to conduct the inspections. When problems are found and the FDA is unable to take enforcement action, the agency plans to refer cases to state officials for further investigation.
Since the outbreak, industry and health-care groups and consumer advocates have called for greater oversight of the manufacturing-style pharmacies that dominate the compounding industry. As pharmacies, they are primarily regulated by state pharmacy boards. But the large companies are multimillion-dollar firms that mass-produce medications and ship them across state lines, often without individual patient prescriptions. They operate more like drug manufacturers, but their compounded medications do not have to pass the same rigorous tests for safety and effectiveness required of FDA-
Critics have complained that the FDA should have been more aggressive, and the House Energy and Commerce Committee is investigating to determine whether the agency has some responsibility for the meningitis outbreak.
FDA officials have said they are stymied by gaps in the law and conflicting court rulings. Companies have ignored orders to fix safety problems and have frequently been able to keep the agency out of their facilities. Congress is considering legislation to address public safety concerns.
In several states, authorities aren’t waiting for the federal government and are taking action their own.
In New York, the state requires patient-specific prescriptions for all prescription-required drugs, including compounded medications. Drug manufacturers authorized by the FDA to produce specific drugs may supply them without a patient-specific order, but only with FDA assurance that they have met the federal safety standards.
In November, the New York state pharmacy board issued a temporary ban on PharMEDium’s products for which there is no patient specific prescription, according to state regulators. In January, New York officials asked FDA Commissioner Margaret Hamburg to inspect PharMEDium “as soon as possible” as part of a process that would allow the company to operate lawfully as a drug manufacturer.
“As you are aware, New York hospitals have grown to rely upon a number of compounded pharmaceuticals. Many of these are compounded by a national pharmacy, PharMEDium,” according to the letter to Hamburg from Education Commissioner John King and Health Commissioner Nirav Shah.
The ban has placed a heavy burden on many New York hospitals. Of 57 hospitals surveyed by the purchasing arm of the Greater New York Hospital Association, 44 percent said they were moderate-to-high users of compounded medications, according to the association’s newsletter.
That has left some New York hospitals scrambling.
“The impact has been that hospitals have had to make these IV preparations themselves, causing much disruption to hospitals’ pharmacy departments,” said hospital association spokesman Brian Conway in an e-mailed statement. Several large hospitals that he declined to identify are having to make more than 5,000 units of these drugs every week, he said.
“It’s certainly less than ideal for hospitals to make these preparations in-house in such large volumes,” he said.