FDA Says It Approved The Wrong Drug Plant
Tuesday, February 19, 2008
The Chinese facility that supplies the active ingredient of the widely used blood thinner heparin was never inspected by the Food and Drug Administration because the agency confused its name with another just like it, agency officials said yesterday.
The FDA said that a team of inspectors is headed now to China to inspect the plant as part of an effort to determine what may have caused a sudden spike in serious problems with the drug, which has been on the market since the 1930s.
More than 350 adverse reactions to the drug have been reported to the FDA since the end of 2007, including a dangerous lowering of blood pressure, breathing difficulties and vomiting. Four patients who took the drug died. One of its two manufacturers, Baxter International, stopped selling its multiple-dose vials of heparin earlier this month, and yesterday the FDA advised doctors to prescribe alternatives.
Millions of people each year are given the drug during dialysis or to prevent complications from surgery, but the FDA has never checked the Chinese plant where the active ingredient is made. The agency and Baxter are investigating whether anomalies in the ingredients from China could have caused the dangerous reactions in some patients.
Joseph Famulare, deputy director for compliance at the FDA's center for drug evaluation and research, said yesterday in a conference call with reporters that when the company that makes the active ingredient for heparin applied for FDA approval, the FDA thought the application had come from a different company with a similar name that had already been inspected.
"To date this is an isolated situation, but the wrong firm was put into the database," he said. Famulare declined to name the Chinese company approved by mistake.
FDA officials said that although federal law does not require inspections of foreign drugmakers, the agency will in most instances inspect before a new foreign drug, or foreign active drug ingredient, is allowed in an FDA-approved prescription medication. That inspection need not include an on-site visit if the foreign company has passed previous inspections for other drugs.
The Government Accountability Office and some members of Congress have concluded that the FDA lacks the resources to inspect thousands of imported drugs and drug ingredients, particularly those coming from India and China.
In a letter to the FDA last week, for example, Rep. John D. Dingell (D-Mich.), chairman of the House Energy and Commerce Committee, said that the heparin situation illustrates the "disastrous state of your agency's foreign inspection program related to pharmaceuticals manufactured abroad."
Dingell noted that the agency seems uncertain even of the number of foreign drugmakers, with one database saying there are 7,000 while another counts 3,000.
Widespread criticism of the FDA's work -- and pressure to change -- followed last year's discovery of tainted pet food from China, as well as lead paint on some toys and barely regulated drugs.
In response, FDA Commissioner Andrew C. von Eschenbach proposed basing FDA inspectors and technical advisers in China, India, the Middle East and three other regions. He also requested that the State Department approve a permanent FDA presence at the U.S. Embassy in Beijing and two American consulates in China.
In the teleconference yesterday, Michael Rogers, director of field investigations for the agency's Office of Regulatory Affairs, said that the heparin investigation is "one of the agency's top priorities" and that inspectors will stay in China until they determine whether health problems associated with the drug originated there. He said the agency is still unsure about the "root cause" of the adverse reactions.
The American market for the generic drug heparin is shared by Baxter and APP Pharmaceuticals. Baxter gets its product from Scientific Protein Laboratories, a Wisconsin-based company that finishes the drug both in the United States and in China, according to Baxter spokeswoman Erin Gardiner. Baxter sells 35 million vials of heparin a year, she said.
The active ingredient used by Baxter and APP is derived from an enzyme found in pig intestines and is made solely in China. But the reported problems have involved only Baxter's version of the drug, which uses an active ingredient from a manufacturing plant started by the Wisconsin firm called Changzhou SPL, west of Shanghai. It was opened in 2004.
According to the FDA, that plant has not been inspected by Chinese drug regulators, who sometimes do not visit facilities manufacturing for foreign markets. Baxter has said that it had sent its own representatives there to ensure proper manufacturing procedures were being followed six months ago.
Gardiner said that the company has detected slight variations between different lots coming from China.
When the application from the Changzhou firm was activated, Famulare said, it was mistaken for another Chinese firm that made a different drug. The FDA accepts previous positive inspections as sufficient proof that a company is doing a good job, and it can approve new drugs or drug ingredients based on that record.