Tainted foreign drugs trigger FDA scrutiny from Congress

Washington -- Food and Drug Administration officials came under congressional fire in April and early May as legislators questioned them about problems that afflict the agency's foreign drug inspection system and sought advice on ways to correct them.

Galvanized by the deaths that resulted from contaminated heparin, Rep. John Dingell (D, Mich.), chair of the House Energy and Commerce Committee, asked FDA officials to name their price for installing proper safeguards to help ensure that such catastrophes don't happen again.

Under sharp questioning, Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, estimated that it would take about $225 million each year for the agency to track and inspect appropriately the hundreds of foreign plants that play roles in the production of medications sent to the U.S. The amount was a giant leap from the $11 million dedicated to such inspections this year.

The FDA's ability to ensure the safety of the nation's drug supply has been questioned numerous times in the past several years, triggered first by the withdrawal from the market of high-profile drugs and now by the deaths of at least 81 people from tainted heparin. The active ingredient was produced in China.

The number of overseas firms supplying ingredients or finished pharmaceuticals to the U.S. market has skyrocketed in recent years, vastly outpacing the FDA's ability to track them, officials acknowledged.

Since 1992, there has been a 400% increase in the number of foreign establishments named in generic drug marketing applications, said Dr. Woodcock during an April 29 hearing before the House Energy and Commerce subcommittee on oversight and investigations.

But a precise number is not available, since the agency's databases do not provide an accurate count of firms subject to inspection, according to an April 22 report by the Government Accountability Office.

Providing the FDA with the funds, authority and equipment to improve its inspection rate of foreign firms is the goal of legislation being drafted by Dingell and others. A May 1 hearing was held by the Energy and Commerce Health Subcommittee to discuss a draft of the legislation -- the Food and Drug Administration Globalization Act. The draft builds on several other drug and food safety bills.

The heparin case

The current focus on global imports was triggered by the importation from China of contaminated raw material for heparin. The contaminating ingredient, oversulfated chondroitin sulfate, is now thought to have been added intentionally.

The raw material was shipped to the U.S. from the Chinese facility, Changzhou SPL, a firm owned jointly by the U.S. firm Scientific Protein Laboratories and Techpool, a Chinese firm that gathers raw heparin from a number of workshops that extract the material from the mucus linings of pig intestines.

Through a chain of human and computer errors, Changzhou SPL was not inspected by the FDA in 2004, as was the agency's intention. But whether this inspection would have caught the contaminated ingredient before it was exported is not known.

Although the Chinese government disputes that the exported product was to blame for the deaths, the FDA and the drug firms involved believe it was the cause. A study published online April 23 by the New England Journal of Medicine also concluded that the manmade oversulfated chondroitin sulfate, which is very hard to detect in heparin, was the likely cause of the severe anaphylactoid reactions that occurred after the intravenous heparin was administered to patients in the United States and Germany.

Dingell's legislation would attempt to address the missteps that allowed these lapses to happen by requiring all drug, medical device and food manufacturers operating within the U.S. or exporting products to the U.S. to register annually with the FDA. Registration would require the payment of a fee, and the $300 million that would result from these user fees would allow inspections to be performed once every two years.

Foreign plants are inspected about once every 13 years, said Dingell, who characterized the FDA's system as one that is "chronically underfunded, with authorities greatly outdated, based on a lot of trust, but very little verification."

The proposal to expand user fees, which already are funding substantial amounts of FDA drug safety work, is raising concern among some legislators and others who would prefer to have the additional funds come from tax revenue, rather than directly from the industry.

"We, as American taxpayers, today spend only 1½ cents per day on the FDA," said William Hubbard, an FDA associate commissioner for 14 years before his retirement. "I believe the vast majority of our citizens would gladly pay 2 or 3 cents a day for an effective FDA that can vigorously protect our food and drug supply." Hubbard is now an adviser to the Alliance for a Stronger FDA, which supports an increase in FDA appropriations.

An increase in public funds for the FDA also was favored by the Pharmaceutical Research and Manufacturers of America, a trade association for pharmaceutical and biotechnology companies.

Meanwhile, the FDA has taken steps to address the problems, having announced in March its intention to establish an office in China. Also, on April 30, the agency launched a hiring initiative for more than 1,300 biologists, chemists, statisticians and investigators. Most of the positions will involve safety monitoring of human and veterinary drugs, biological products, medical devices, food, cosmetics and products that emit radiation.