FDA Admits to Lacking Control Over Counterfeit Drug Imports
"There are problems. I fully acknowledge that," said Dennis Baker, associate commissioner for regulatory affairs, who came to FDA a year ago from the Texas health department.
For nearly two years, the House Commerce Committee has been investigating FDA's record for intercepting imports of counterfeit and substandard bulk drugs.
Yesterday's investigative hearing sought to follow up on information provided by FDA Commissioner Jane E. Henney at the committee's request.
From what the committee has learned, said Chairman Tom Bliley (R-Va.), FDA cannot assure the American public that the agency protects citizens from counterfeit, unapproved, or substandard drugs.
"The FDA admits there are about 4,600 foreign drug manufacturers that have shipped to the U.S. since October 1997 but have never been inspected by the FDA, including 623 in China and 409 in India," said Bliley in a statement issued shortly before the hearing. "Many times FDA will allow drug products into our country not based on proof of authenticity, but merely on the representations of an international broker, who could in fact be the counterfeiter."
One example cited by Bliley and other committee members as a gaping hole in FDA's inspection system involves bulk gentamicin sulfate that two U.S. companies used to manufacture injectable drug products.
Flavine International, a New Jersey-based broker of bulk drugs, bought bulk gentamicin sulfate at a relatively low price from unapproved sources in China. The broker repackaged the bulk drug to resemble gentamicin sulfate manufactured by Long March Pharmaceutical Plant, an FDA-approved manufacturer in China, and sold the counterfeit drug to Fujisawa USA and ESI Lederle.
FDA's criminal investigation of Flavine initially focused on oxytetracycline, an animal drug that the broker also bought from unapproved sources and repackaged to look like a Long March product. Further investigation revealed that the broker had counterfeited gentamicin sulfate and other bulk drugs used in the manufacture of human prescription drugs.
According to Bliley's review of the case, FDA's investigative team received information about adverse events related to the administration of gentamicin. The vast majority of these events were linked to products manufactured by Fujisawa and its Lyphomed Division and Solopak Laboratories. The final investigatory report did not mention any planned follow-up with these or any generic drug companies to ensure no products made from the counterfeit bulk material remained on the U.S. market.
Two years later, Morbidity and Mortality Weekly Report published an account of more than 57 endotoxin-like reactions related to the administration of gentamicin injection manufactured by Fujisawa. The next year, in 1998, Fujisawa and ESI Lederle, another generic drug manufacturer, voluntarily withdrew lots of gentamicin injection.
Bliley, in a May 8 letter to Commissioner Henney, noted that FDA recommended only as recently as September 1999 for its import inspectors to automatically detain gentamicin sulfate manufactured by Long March. FDA inspection of the bulk drug and accompanying paperwork in August 1999 had revealed numerous deviations from U.S. good manufacturing practices, including problems with monitoring and control of the water system and with laboratory controls.
Despite the information detailed by Bliley, FDA's Baker said, "We still believe that the overall quality of drug products in this country is high."
To correct the problems, Baker said, FDA must integrate its databases, allocate more personnel to the regulatory effort, and find a way to determine the actual manufacturer of a bulk drug.
Baker described FDA's plans for improving the situation:
- Continue to meet with representatives from U.S. industry and other countries' governments [the list of countries did not include China or India],
- Strengthen surveillance activities by collecting more samples of active pharmaceutical ingredients manufactured in other countries and requesting authentic information about the ingredients,
- Educate FDA import inspectors about U.S. Customs Service laws and regulations,
- Give import inspectors access to the FDA database that tracks drug applications, which contain information about suppliers,
- Enhance the ability of FDA forensic chemists to analyze active pharmaceutical ingredients,
- Develop a strategy for inspecting U.S. import agents and brokers,
- Use "import alerts" to disseminate information about problems with imported products.
FDA has 175 full-time-equivalent employees available to inspect foreign drug manufacturers, Baker said, but these personnel also perform domestic inspections. Redirecting more hours to foreign inspections would mean spending less time on domestic inspections.
Baker said FDA is considering its regulatory options for requiring U.S. manufacturers to report when they find counterfeits in bulk drug imports.
John Taylor, acting director of the office of compliance at FDA's Center for Drug Evaluation and Research, himself only six weeks at this position, said U.S. manufacturers have not suggested to FDA that they report problems when found.
Before departing, after a day on which the committee clearly would have preferred questioning the FDA Commissioner rather than a fairly new associate commissioner, Baker promised to inform members of FDA's difficulties and needs in correcting the problem with counterfeit bulk drugs.