CHINA: Tainted Drugs Tied to Maker of Abortion Pill

Publisher Name: 
The New York Times

BEIJING - A huge state-owned
Chinese pharmaceutical company that exports to dozens of countries,
including the United States, is at the center of a nationwide drug
scandal after nearly 200 Chinese cancer patients were paralyzed or otherwise harmed last summer by contaminated leukemia drugs.

Chinese drug regulators have accused the manufacturer of the tainted
drugs of a cover-up and have closed the factory that produced them. In
December, China's Food and Drug Administration
said that the Shanghai police had begun a criminal investigation and
that two officials, including the head of the plant, had been detained.

The drug maker, Shanghai Hualian, is the sole supplier to the United States of the abortion pill, mifepristone, known as RU-486. It is made at a factory different from the one that produced the tainted cancer drugs, about an hour's drive away.

The United States Food and Drug Administration declined to answer
questions about Shanghai Hualian, because of security concerns stemming
from the sometimes violent opposition to abortion. But in a statement,
the agency said the RU-486 plant had passed an F.D.A. inspection in
May. "F.D.A. is not aware of any evidence to suggest the issue that
occurred at the leukemia drug facility is linked in any way with the
facility that manufactures the mifepristone," the statement said.

When told of Shanghai Hualian's troubles, Dr. Sidney M. Wolfe,
a leading consumer advocate and frequent F.D.A. critic, said American
regulators ought to be concerned because of accusations that serious
health risks had been covered up there. "Every one of these plants
should be immediately inspected," he said.

The director of the Chinese F.D.A.'s drug safety control unit in
Shanghai, Zhou Qun, said her agency had inspected the factory that
produced mifepristone three times in recent months and found it in
compliance. "It is natural to worry," Ms. Zhou said, "but these two
plants are in two different places and have different quality-assurance
people."

The investigation of the contaminated cancer drugs comes as China is
trying to restore confidence in its tattered regulatory system. In the
last two years, scores of people around the world have died after
ingesting contaminated drugs and drug ingredients produced in China.
Last year, China executed its top drug safety official for accepting
bribes to approve drugs.

Shanghai Hualian is a division of one of China's largest
pharmaceutical companies, the Shanghai Pharmaceutical Group, which owns
dozens of factories. Neither Shanghai Hualian nor its parent company
would comment on the tainted medicine.

Last week, The New York Times asked the F.D.A. whether the Shanghai
Pharmaceutical Group exported to the United States any drugs or
pharmaceutical ingredients other than the abortion pill. But after
repeated requests, the agency declined to provide that information; it
did not cite a reason.

On at least two occasions in 2002, Shanghai Hualian had shipments of
drugs stopped at the United States border, F.D.A. records show. One
shipment was an unapproved antibiotic
and the other a diuretic that had "false or misleading labeling."
Records also show that another unit of Shanghai Pharmaceutical Group
has filed papers declaring its intention to sell at least five active
pharmaceutical ingredients to manufacturers for sale in the United
States.

One major pharmaceutical company, Pfizer,
declined to buy drug ingredients from Shanghai Pharmaceutical Group
because of quality-related issues, said Christopher Loder, a Pfizer
spokesman. In 2006, Pfizer agreed to evaluate Shanghai Pharmaceutical
Group's "capabilities" as an ingredient supplier, but so far the
company "has not met the standards required by Pfizer," Mr. Loder said
in a statement.

Because of opposition from the anti-abortion movement, the F.D.A.
has never publicly identified the maker of the abortion pill for the
American market. The pill was first manufactured in France, and since
its approval by the F.D.A. in 2000 it has been distributed in the
United States by Danco Laboratories. Danco, which does not list a
street address on its Web site, did not return two telephone calls
seeking comment.

Problems with the cancer drugs first surfaced last summer after
leukemia patients received injections of one cancer drug, methotrexate.
Afterward, patients experienced leg pain and, in some cases, paralysis.
At the People's Liberation Army No. 307 Hospital in Beijing, a
26-year-old patient, Miao Yuguang, was unable to stand up five days
after being injected in the spine with the drug. "We were already
unlucky to have this illness," her father, Miao Futian, said of the
leukemia. "Then we ran into this fake drug."

The authorities recalled two batches of the drug, but issued only
mild warnings because the cause of the problem was unclear. Officials
with Shanghai Pharmaceutical Group stood by their products, saying that
drug regulators investigating the plant had found no problems. But when
another cancer drug made in the same factory - cytarabin hydrochloride
- also began causing adverse reactions, investigators suspected
contamination.

In September, health and drug officials announced that they had
found that the two drugs were contaminated with vincristine sulfate, a
third cancer drug, during production. After issuing a nationwide alert,
the government announced a wider recall, and Shanghai's drug agency
sealed manufacturing units at the plant.

"Many people thought there was a problem with the hospitals,"
said Zheng Qiang, director of the Center for Pharmaceutical Information
and Engineering Research at Peking University. "It wasn't until later
that they discovered the problem was with the medicine."

Chinese media attention on the case has surged, after a terse
statement by China's drug agency in December, accusing Hualian company
officials of a systematic cover-up of violations at the facility that
made the drugs.

Family members at the No. 307 hospital have counted 53 victims in
Beijing, and say they were told that there were least 193 victims
nationwide. It is unclear how many were paralyzed, because the
authorities have not released an official figure. Relatives have joined
to share information and advocate for the victims. Based on interviews
with several families in Beijing and Shanghai, it appears that about
half of those injected still cannot walk.

Wu Jianhua said his daughter, Wu Xi, 15, collapsed on her way to
school after an injection in August. "We thought she was tired," Mr. Wu
said. Doctors now say she may never walk without a cane, he said.

Last week, on a window near the gate of the closed plant was a
notice from the Shanghai Food and Drug Administration, dated Sept. 8,
accusing the plant of "producing substandard medicine that poses major
risks of causing serious harm to human health." It identified a company
official, Gu Yaoming, as the "person responsible" for the plant.

Records show Mr. Gu also met with the United States F.D.A.
inspectors last May as part of the routine inspection of the plant that
makes RU-486.

Reached by telephone, Mr. Gu declined to describe his role at the two plants. "I cannot answer your questions," he said.

A spokeswoman for China's Food and Drug Administration, Yan
Jiangying, said that Shanghai Hualian had been stripped of its license
to produce antitumor drugs, but that this action did not affect RU-486.

Hualian is the latest in a string of tainted medicine cases that
have undermined confidence in the safety of drugs here. In 2006, at
least 18 Chinese died after an intravenous drug used to treat liver disease,
Armillarisin A, was laced with diethylene glycol, a toxic chemical used
in some antifreeze. Also in 2006, at least 14 Chinese died after taking
a Chinese antibiotic, Xinfu, which was not properly sterilized during
production. And more than a hundred people died in Panama after taking
cold medicine containing a mislabeled and toxic chemical from China.

In each of these cases, the manufacturer failed to follow good manufacturing practices to ensure the final product was safe.

Describing the cover-up at the factory, Ms. Zhou, the regulator who
led the investigation, said workers did not tell investigators that
vincristine sulfate - a drug too toxic for use in spinal injections -
had been stored in a refrigerator with materials for other drugs.

"At the time, we didn't think they had lied to us," Ms. Zhou said.
The deception sent investigators on a two-month hunt for other possible
causes of the adverse reactions. "If they had been open about the
vincristine sulfate in the beginning, maybe fewer people would have
been harmed," she added.

While regulators have accused factory employees of a systematic
cover-up of violations in production, they have not said whether
superiors at Shanghai Pharmaceutical were aware of it. "We'll have to
wait until the police investigation is finished" to make more details
public, said Ms. Yan, the drug agency spokeswoman.

Mr. Zheng at Peking University said that producing multiple drugs in
a single workshop was risky, but that some Chinese companies saw it as
a way to save money. "It was an accident," he said of the Hualian case.
"But it was bound to happen."


Jake Hooker
reported from Beijing and Shanghai, and Walt Bogdanich from New York.
Andrew Lehren contributed reporting from New York.

AMP Section Name:Pharmaceuticals
  • 182 Health
  • 185 Corruption
  • 195 Chemicals