Can we trust a Chinese manufacturer that not only sold contaminated
cancer drugs but tried to cover up the fact? Apparently, the FDA thinks so. Shanghai Hualian is the sole U.S. supplier of
mifepristone (RU-486), the abortion pill. It's also the company under criminal investigation in China for selling tainted
leukemia drugs. And the FDA simply won't say whether the company exports any other drugs or pharma ingredients to the U.S.
The mifepristone is made in an entirely different plant run
by the company, yes. And--unlike a host of long-uninspected foreign facilities--the FDA inspected this one as recently as May. It passed. China's FDA also has given the plant three look-sees in the last
few months and proclaimed it clean. But Chinese regulators also have accused the company of a systematic cover-up of violations
at the cancer drug facility.
At least one American drug maker--Pfizer--refuses to buy drug
ingredients from Shanghai Pharmaceutical Group because of quality problems. Consumer advocates say Shanghai's problems demand
additional scrutiny. "Every one of these plants should be immediately inspected," one told 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. {Likely reason is that the FDA doesn’t
require the Pharmaceutical industry to report to them their sources—jk.}
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.”
ake Hooker reported
from Beijing and Shanghai, and Walt Bogdanich from New York.
Andrew Lehren contributed reporting from New York
