Cherry Hill manufacturer caught in drug flap

A South Jersey manufacturing plant has found itself at the center of an international imbroglio over contamination in a blood-thinning drug linked to severe allergic reactions and as many as 81 deaths.

Baxter International Inc.'s Cherry Hill plant - a complex of one-story buildings near Springdale Road and surrounded by a black metal security fence - turns out 35 million vials of injectable heparin a year, or about half the U.S. supply for hospitals and medical centers.

In January, Baxter began getting increased reports of severe patient reactions - shortness of breath, low blood pressure, nausea and abdominal pain. In February, the Deerfield, Ill., drugmaker voluntarily recalled all its heparin doses and temporarily stopped manufacturing the drug at its Cherry Hill plant.

The 800 employees who work there manufacture more than 100 products, including sedatives, antihistamines, and drugs to treat nausea and vomiting caused by cancer chemotherapy, radiation and surgery.

The Food and Drug Administration inspected the Cherry Hill plant in February and gave it a clean bill of health. The FDA is looking at a contaminant, oversulfated chondroitin sulfate, that the agency discovered in material supplies of heparin coming from China.

The FDA has established, through animal tests, a biologic link between the contaminant and allergic reactions.

The FDA released a "warning" letter yesterday to a Chinese material supplier, Changzhou SPL, citing "significant deviations" from good manufacturing practices.

The Chinese said they wanted to get some samples from the Cherry Hill plant to conduct their own investigation.

Chinese scientists today visited the Baxter plant in Cherry Hill for the samples.

"This is basically a courtesy we extended to host them since they were in the states attending an FDA regulators' meeting," said Baxter spokeswoman Erin Gardiner.

"We are evaluating their request" to take heparin samples to China. "I'm not going into any more detail," she added.

Meanwhile, Baxter said it investigated on its own and confirmed that Cherry Hill was "not the root" of the contaminant. It contends the contaminant was introduced earlier in the supply chain - in China - before reaching Baxter's Wisconsin supplier, Scientific Protein Laboratories L.L.C. Changzhou SPL, the focus of the FDA warning letter, is a joint venture with Scientific Protein Labs.

The dispute reached a crescendo yesterday after a briefing at the Chinese Embassy in Washington, where a Chinese official disputed that oversulfated chondroitin was the cause of the reactions.

Jin Shaohong, deputy director of the National Institute for the Control of Pharmaceutical and Biological Products in China, said officials had analyzed several batches of heparin ingredients and concluded that some batches causing allergic reactions in the United States did not contain the suspected contaminant.

Shaohong said one heparin batch that generated 100 reaction reports - 25 of them serious - did not contain the contaminant. The Chinese do not "support the theory" that the root cause was a contaminant.

FDA spokeswoman Karen Riley responded that the FDA tested from the same heparin lot "and we have found contaminant."

"They [Chinese] have used a different test, not the one the international community is using to screen for contaminants. It has less sensitivity and specificity, and it is especially not as good when you have a smaller percentage of contaminant in the drug.

Riley said, "We are convinced that this particular lot did have contaminant, based on our testing."

The FDA said 11 countries have reported contaminated heparin. "We don't know where the contaminant was entered in the supply chain," agency spokeswoman Heidi Rebello said.

Today, Dao Dong Wang, spokesman for the Chinese Embassy, said that Chinese authorities had not excluded "any possibilities as to the cause of the problem related to heparin. It's still an open question."

Wang added: "The adverse effects might be the result of a contaminant in a heparin product that came from a Chinese factory. It might, and it might not. The problem might be at any place along the way," he said.

"It's not the intention of the Chinese to exchange charges with the U.S., but to share with the media their impression - it's still open as to the root cause of this heparin problem."

Heparin is an anticoagulant for patients undergoing surgery, blood transfusions, and other treatments requiring a blood-clotting inhibitor. It is derived from pig intestines and processed by unregistered workshops and consolidators in China.

Baxter's plant sits in the Cherry Hill Industrial Park, squeezed between the New Jersey Turnpike and Springdale Road. Around the brick factory and mostly one-story office buildings there is little pedestrian traffic, and employees come and go by car, driving through gates opened with key cards.

Two women, taking a cigarette break at a set of picnic tables just outside the fencing yesterday afternoon, said they were not allowed to speak to a reporter.

Later, two Baxter security guards asked several photographers to move away from the plant's main gate, on Olney Avenue, which led into a massive parking area.

The other major U.S. supplier of injectable heparin, APP Pharmaceuticals Inc., of Schaumburg, Ill., is continuing to manufacture heparin and screening its supplies for contaminants.