FDA cites Chinese firm's manufacturing processes for heparin
By KEVIN FREKING – 1 hour ago

WASHINGTON (AP) — The Food and Drug Administration has told the Chinese manufacturer of a heparin ingredient that it does not have adequate systems for ensuring that the raw materials it uses are safe and that any impurities are removed.

The FDA released a warning letter Monday to Changzhou SPL Co., hours after Chinese officials voiced doubts that a contaminant identified in the blood thinner heparin caused severe allergic reactions in hundreds of U.S. patients.

The FDA told Changzhou SPL that it had "significant deviations" from good manufacturing processes. Until it complies, the agency will recommend disapproval of any new applications listing the company as the manufacturer of any active pharmaceutical ingredient.

THIS IS A BREAKING NEWS UPDATE. Check back soon for further information. AP's earlier story is below.

WASHINGTON (AP) — Chinese officials voiced doubts Monday that a contaminant identified in the blood thinner heparin was the root cause of severe allergic reactions in hundreds of Americans.

The officials suggested at an embassy news conference that the problem with the drug could have occurred in the United States. They plan to visit a Baxter International plant in Cherry Hill, N.J., to get a better picture of how the finished product is manufactured.

"When you see it, then you believe it," said Jin Shaohong, the deputy director general for the National Institute for the Control of Pharmaceutical and Biological Products in China.

Raw heparin is derived from pig intestines, often processed by small, unregistered workshops in China. The raw ingredient for Baxter's recalled heparin came from Wisconsin-based Scientific Protein Laboratories, which in turn owns a Chinese factory — Changzhou SPL — and buys additional raw heparin from other Chinese suppliers.

Health and Human Services Secretary Mike Leavitt said that officials with the Food and Drug Administration would respond to the Chinese concerns later Monday. He said that he's seen progress in how China has address safety concerns, and he would be surprised if it didn't take strong steps to address any problems found with the manufacturing process for heparin.

The Food and Drug Administration has counted 62 deaths from allergic-style reactions that were associated with recalled heparin batches. The FDA can't say for sure what caused the reactions, but the chief suspect is a contaminant that the agency discovered in supplies of raw heparin coming from China — a compound derived from animal cartilage that so closely mimics heparin that routine purity tests can't detect it.

Germany also discovered the contaminant and recalled batches of heparin after some patient illnesses.

But the Chinese officials contended Monday that batches not containing the contaminant — called oversulfated chondroitin — also have been associated with side effects.

"The oversulfated chondroitin can therefore not be a suspected root cause of heparin adverse events as reported in U.S. media previously," Shaohong said.

Baxter denied that claim.

"We do not agree with that," said Baxter spokeswoman Erin Gardiner. "We have seen adverse event reports on batches where the contaminant has been confirmed to be present."

Baxter was considering the Chinese officials' request for additional heparin samples for their own further testing, Gardiner said.

The Chinese officials also said that aside from the U.S. and Germany, more than 10 other countries used heparin containing the contaminant to produce their final injection but reported no side effects. Also, one batch of heparin injections free of the contaminants has resulted in about a hundred adverse events, of which 25 were serious.

The officials also noted that the implicated Chinese factory — Changzhou SPL — was managed and overseen by a manager from its U.S. headquarters. The heparin ingredient produced by the factory has all been exported.

"None has been sold into the Chinese domestic market," Shaohong said.

I went through a recall scare when heart valves were recalled. I was one number off and had the code recorded in my medical record.

In taking Heparin a recall is real concern but the fact its a sulfide worries me also as I am allergic to those as additives in medications.

Its worth checking out so I went to Baxter websites and have posted what they had for the recall.

http://www.baxter.com/products/biopharmace...ls/heparin.html

2008 Heparin Recall Information


Customers with questions about Baxter's U.S. vial-based heparin product recall may call the Center for One Baxter at 1-800-4-BAXTER (1-800-422-9837). Representatives are available Monday through Friday from 8 a.m. - 5 p.m. Central Daylight Time.



Press Releases

* Baxter to Proceed with Recall of Remaining Heparin Sodium Vial Products
February 28, 2008

* Baxter Provides Update on Heparin Reactions
February 11, 2008

* Baxter Issues Urgent Nationwide Voluntary Recall of Heparin 1,000 Units/ML 10 and 30mL Multi-Dose Vials
January 25, 2008

Press Updates

* March 19, 2008 Heparin Update

FDA Chief Faces Wrath of Congress
Lawmakers Say Contaminated Blood Thinner Illuminates Problems With Drug Supply
By MATTHEW JAFFE

April 22, 2008—

Under the cloud of contaminated heparin deaths, Food and Drug Administration Commissioner Andrew von Eschenbach received a rude welcome from Congress Tuesday, accused by Rep. John Dingell, D-Mich., of "carrying the water" for the Bush administration, "toe-dancing around the hard facts," and making promises that turn out to be nothing more than "hooey."

"Commissioner, I have no ill will towards you," Dingell said. "I have ill will of the most gross sort towards the fact that you come up here and defend a situation that is indefensible and that you are not soliciting the resources that you need to do your job to protect the American people the way the law says you should. And that you are tolerating an administration which is allowing this kind of situation to continue, because they are too damn tight to see to it that the American people have the funds that are necessary to protect them against wrongdoing in foreign countries."

Estimates suggest more than 80 percent of all active ingredients used by U.S. drug manufacturers come from abroad. But the FDA only inspects foreign drug plants about once every 13 years, compared to every two to three years for domestic plants, according to the Government Accountability Office. The GAO finds that China's drug plants are inspected once every 30 to 40 years.

FDA officials said Monday that as many as 81 deaths and hundreds of severe reactions among patients taking the blood thinner heparin have been traced to a man-made contaminant from China. Chinese officials disputed these claims, saying the contaminant is not the cause of the problems.

In light of the heparin situation, von Eschenbach told lawmakers at Tuesday's hearing of his plans to improve the FDA's system that currently inspects only about 10 to 20 of China's 700 registered drug firms per year.

He said the agency's response to growing challenges in a "rapidly and radically changing world" has not been adequate.

"In addition to addressing the need to increase our inspections, we also need to overhaul the entire system," von Eschenbach said.

The FDA plans to establish permanent overseas offices in numerous countries, including China, to help address the problem. More foreign plant inspections than ever were conducted by the FDA in 2007, dedicating about $10 million to the process. But GAO analysis said it would cost the FDA $67 to $71 million each year to inspect the thousands of foreign plants on the agency's priority list.

Still, von Eschenbach told the House Subcommittee on Oversight and Investigations that in heparin's case, even if the Chinese plant had been inspected years ago, "we would not have detected that contamination" because the test to detect it was just developed.

But subcommittee chairman Bart Stupak, D-Mich., disagreed, arguing that "the lack of inspections actually encourages a less safe product in some of these plants."

"I've been talking to Food and Drug Administration commissioners for 40 years," Dingell said. "And you're not the first fella I've had to skin for not doing his job and coming up here and defending an indefensible situation. So, I want to maintain my respect for you but I can't maintain my respect for you if you keep toe-dancing around the hard facts that curse you with the inability to do your job because you don't have the resources."

The GAO's health care director, Marcia G. Crosse, said that, although the FDA is making progress, short-term risks still remain.

"FDA's plans represent a step forward in filling the large gaps in FDA's foreign drug inspection program, but do little to accomplish short-term change," Crosse said.

The GAO said, as early as 1998, that the FDA needed to improve its foreign drug inspection program. Last November, the GAO released a report revealing that the FDA was unaware how many foreign drug makers were sending their drugs to the U.S.

The GAO noted one database showed 3,000 registered makers and another revealed that 6,800 makers actually shipped their drugs into the country last year. The report placed blame on a serious lack of human and economic resources, flaws in FDA databases and IT systems, and inadequate permanent operational support in foreign countries.

"How can there be any confidence that the FDA is adequately regulating foreign drug firms when the FDA has no idea who's making what, where they are physically located, and when they were last inspected?" asked Stupak.

"Last year, this nation's regulatory failures resulted in dead dogs and cats; this year, it has tragically led to the deaths of people," Stupak said. "If we don't make some rapid progress on fixing the foreign drug inspection program, the next 'melamine' or 'heparin' tragedy will soon be upon us."

"The FDA can be re-built but it will be expensive," said Carl Nielsen, retired director of the FDA's office of regulatory affairs. "The public health cost is higher, though, if no significant investment is made, as demonstrated by the heparin incident."