- House panel says FDA hasn't acted swiftly on Chinese materials
- Contaminated heparin linked to 246 fatalities in 2007 and 2008
Heparin tainted with unauthorized Chinese-made ingredients may be on the market in the U.S. and the Food and Drug Administration hasn’t moved swiftly enough to prevent it, according to a congressional probe nearly a decade after hundreds of deaths were linked to sullied batches of the blood-thinning drug.
This possible contamination is different from the earlier one, when Chinese producers made crude heparin containing a deadly chemical. They may be using cow and sheep intestines to produce the raw material for heparin that is supposed to be derived only from the intestinal membranes of pigs, according to a letter the House Energy and Commerce Committee sent Tuesday to the FDA. The agency has known about the risky practice since 2007, around the time it discovered the chemically enhanced crude heparin, the panel said.
The FDA didn’t react early on “to credible evidence of non-porcine contamination of the Chinese heparin supply,” according to the letter, only putting out testing guidelines for pharmaceutical companies in 2012. Even after the tragedy of the chemically soiled heparin, the committee said, “loopholes and exemptions that permit part of the Chinese drug supply chain to operate outside government scrutiny still remain.”
Christopher Kelly, a spokesman for the FDA, said the agency would respond to directly to the committee and declined to comment. The letter was signed by five Republican leaders of the panel, including Chairman Fred Upton of Michigan. The committee investigation was based on government and industry documents and interviews.
The allegations in the letter renew worries over how potentially dangerous pharmaceuticals, particularly from China, can reach world markets, as well as authorities’ ability to police vast global supply chains.
The chemical, oversulfated chondroitin sulfate, was connected to 246 deaths and sickened hundreds of people who took the blood-thinning medicine, the FDA said at the time. Regulators never found at what point in the chain in China that the drug, sold in the U.S. by Baxter International Inc., was corrupted. The FDA closed its initial criminal investigation after it became difficult to obtain evidence in China, though it has since re-opened a related inquiry, according to the House committee. Baxter, which recalled its heparin in 2008, hasn’t sold the anticoagulant since. It said at the time it was alarmed that the contamination appeared to have been deliberate, but had no proof of how it happened.
When Baxter’s heparin was recalled, APP Pharmaceuticals Inc., a subsidiary of Fresenius SE & Co. KGaA, shared the U.S. heparin market with Baxter and was able to step up production to become the major supplier. A handful of companies have FDA approval to sell heparin in the U.S. including Fresenius, Pfizer Inc., Novartis AG, Sagent Pharmaceuticals Inc. and B. Braun Medical Inc. The drugmakers didn’t respond to requests for comment on the letter.
The manufacturer of the active ingredient for Baxter’s heparin was a plant in China owned by Scientific Protein Laboratories. Shenzhen Hepalink Pharmaceutical Co. in China agreed to acquire Wisconsin-based Scientific Protein Laboratories for $337.5 million in 2013.
The letter from the House committee said the FDA dropped the ball on many fronts and may have allowed unsafe blood thinners to remain on the market longer than necessary. Regulators didn’t properly or widely enough share information and didn’t follow up on leads about tainted heparin from other governments, according to the letter. Agency investigators failed to inform others about dodgy crude heparin makers, the panel said. It also said the FDA didn’t follow up on concerns that heparin with the chemical was recycled after the poison was removed and may have entered the U.S. market. The claims are based on documents that Baxter, Scientific Protein and FDA provided the committee as well as interviews with FDA employees, according to footnotes in the letter.
The committee asked the FDA to answer a series of questions by April 12, including what actions it’s taken to improve internal communication, whether it takes into account raw material shortages in its inspection strategy, whether it has investigated the potential recycling of contaminated heparin and what it could do to improve its probes of “economically motivated adulteration.”
The U.S. depends heavily on China for medicine. Along with India, the country is one of the top two producers of base ingredients for drugs in the world, according to the National Academies of Sciences, Engineering, and Medicine. The FDA has made inspections in China a priority, and has barred more than 40 plants from exporting some or all of their products to the U.S. In addition, the FDA has banned 34 heparin plants in China from supplying the U.S. because they either don’t meet manufacturing standards or refuse to allow the agency to conduct inspections.
Studies show heparin made from cows rather than pigs works differently in the body, the letter said. The French National Agency for Medicines and Health Products Safety called non-pig blending a “critical” violation in an inspection report released in February. France cited China’s Dongying Tiandong Pharmaceutical Co. for making heparin with ruminant DNA, which includes cows and sheep. Dongying is registered with the FDA as a manufacturer of active ingredients and isn’t on the agency’s list of companies banned from importing to the U.S.
Insufficient Pig Supply
China is the major supplier of crude heparin to the U.S. because of its abundant pig supply, according to the U.S. Government Accountability Office. Thousands of pig farms extract and process the intestines that are collected by consolidators who sell them to manufacturers that refine them. Investigators with the House committee conducted a statistical analysis and determined there aren’t enough pigs in China to create all the heparin material being sold by producers in that country.
“The pig supply in legal slaughterhouses in China would not be sufficient to support the number of pigs needed to manufacture the amount of Chinese heparin for export alone, not even taking into account the amount needed for the Chinese domestic heparin market,” according to the letter to the FDA. The panel ran numbers for 2007 and found China was 100 million pigs short, with analyses for following years showing similar shortfalls, the letter said.
The agency considers heparin adulterated if it contains oversulfated chondroitin sulfate or non-pig material, according to an FDA document for the pharmaceutical industry on monitoring heparin quality. Material from cows could pose a risk because of possible contamination with mad cow disease.