The Invisible Killer Lurk Beneath the Chinese Bargain -- Blood Thinner
Might Be Tied to More Deaths/NYTimes

The New York Times

February 29, 2008

Blood Thinner Might Be Tied to More Deaths

By WALT BOGDANICH

Amid indications that more people may have died or been harmed after
being given a brand of the blood thinner heparin, federal drug
regulators said Thursday that they had found “potential deficiencies” at
a Chinese plant that supplied much of the active ingredient for the drug.

Baxter International, which makes the brand of heparin associated with
the problems, and buys supplies from the Chinese plant, announced that
it was expanding a recall to include virtually all its heparin products.
Though Baxter produces much of the heparin used in the United States,
regulators said the other major supplier would be able to meet the demand.

The Food and Drug Administration said the number of deaths possibly
associated with the drug, made from pig intestines, had risen to 21 from
4. But it cautioned that many of those patients were already seriously
ill and that the drug might not have caused their deaths.

The F.D.A. emphasized that it had yet to identify the root cause of the
problem, and that it had not concluded that the Chinese plant was
responsible. The agency also said it was investigating two Chinese
wholesalers ― also called consolidators ― that supplied crude heparin to
the Chinese plant, Changzhou SPL, as well as those that sold raw
ingredients to the consolidators.

The New York Times reported Thursday that at least one of the
consolidators received supplies from small, unregulated family workshops
that scraped mucous membrane from pig intestines and cooked it,
eventually producing a dry substance known as crude heparin.

The F.D.A. admitted this month that it had violated its own policy by
failing to inspect SPL, located west of Shanghai, before the factory
began shipping the heparin ingredient to Baxter in 2004. China’s drug
agency also did not inspect the plant.

Last week, the F.D.A. sent inspectors to the plant. Among the potential
problems they found was a failure to properly follow the steps for
identifying impurities and deficiencies related to manufacturing
equipment. According to a redacted inspection report released by the
agency, the SPL plant appeared to have made at least some heparin with
“material from an unacceptable workshop vendor.” The vendor was not
identified.

Scientific Protein Laboratories, a Wisconsin company that is the
majority owner of the Chinese plant, issued a statement Thursday saying
the F.D.A.’s finding did not represent its final determination as to
whether the plant complied with federal regulatory rules. S.P.L., the
statement said, is committed to finding the root cause of the adverse
reactions.

Erin Gardiner, a spokeswoman for Baxter, said the company was reviewing
the F.D.A.’s report. “We expect S.P.L. to respond to those observations
thoroughly and promptly,” Ms. Gardiner said. “The observations are
important and need to be addressed promptly but they are not necessarily
indicative of the root cause.”

The F.D.A.’s concern about heparin had previously centered on Baxter’s
multidose vials, but on Thursday Baxter agreed to voluntarily recall not
only the multi-dose vials but also single-dose vials and a diluted
solution of heparin used to keep blood clots from forming in intravenous
lines. There have been no adverse reaction reports involving the latter
product, called Hep-Lock heparin flush products.

“We have assurance from the U.S. Food and Drug Administration that there
is an adequate supply in the market to meet the demand for these
critical and lifesaving drugs,” Peter J. Arduini, president of Baxter’s
Medication Delivery business, said in a statement released by the company.

The only heparin products made by Baxter that are still on the market
are premixed bags of intravenous solutions, the Food and Drug
Administration said.

“We at the F.D.A. understand how unsettling this whole situation with
heparin is,” said Dr. Sandra Kweder, the agency’s deputy director,
Office of New Drugs, Center for Drug Evaluation and Research. “We are
determined to get to the root cause.”

The F.D.A. estimates that more than one million multidose vials of
heparin are sold per month in the United States, about half of which are
manufactured and distributed by Baxter.

The problems with heparin, which is used to prevent blood clotting
during dialysis and after some surgery, were first reported last month
at a hospital in Missouri. Since then, the number of reported adverse
reactions has risen to 448, the F.D.A. said. “Yes, we have gotten more
and we are continuing to evaluate those reports,” Dr. Kweder said.

At first, the agency said it believed that four people had died after
allergic reactions to the drug. On Thursday, officials said as many as
17 more people may have died, but they described the links to heparin as
more tenuous.

The adverse reactions have included decreased or low blood pressure and
fast heart rate. Not all of them are known to involve Baxter products,
but the drug agency did not issue warnings involving any other products.

The Chinese heparin market has been in turmoil over the last year, as
pig disease has swept through the country, depleting stocks, leading
some farmers to sell sick pigs into the market and forcing heparin
producers to scramble for new sources of raw material.

As a result, even big companies have been turning increasingly to small
village workshops, which are often unsanitary. In interviews this week
at some of these workshops, employees told The Times that they had not
been inspected by the government.

Scientific Protein Laboratories said it responded to the disease
outbreak by buying less raw material in China. Its president, David
Strunce, said in an interview this week that the Chinese plant bought
supplies only from two reputable consolidators, and that its suppliers
were audited.

The F.D.A has already finished inspecting one of the consolidators and
is still looking at the second one, an agency spokeswoman said. The
agency also plans, if necessary, to look at some of the small workshops
that supply the consolidators.

“We will go where the investigation takes us,” an agency official said.