NYTimes.com Article: 2 Paths of Bayer Drug in 80's: Riskier Type Went Ov

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2 Paths of Bayer Drug in 80's: Riskier Type Went Overseas

May 22, 2003
By WALT BOGDANICH and ERIC KOLI 




 

A division of the pharmaceutical company Bayer sold
millions of dollars of blood-clotting medicine for
hemophiliacs - medicine that carried a high risk of
transmitting AIDS - to Asia and Latin America in the
mid-1980's while selling a new, safer product in the West,
according to documents obtained by The New York Times. 

The Bayer unit, Cutter Biological, introduced its safer
medicine in late February 1984 as evidence mounted that the
earlier version was infecting hemophiliacs with H.I.V. Yet
for over a year, the company continued to sell the old
medicine overseas, prompting a United States regulator to
accuse Cutter of breaking its promise to stop selling the
product. 

By continuing to sell the old version of the life-saving
medicine, the records show, Cutter officials were trying to
avoid being stuck with large stores of a product that was
proving increasingly unmarketable in the United States and
Europe. 

Yet even after it began selling the new product, the
company kept making the old medicine for several months
more. A telex from Cutter to a distributor suggests one
reason behind that decision, too: the company had several
fixed-price contracts and believed that the old product
would be cheaper to produce. 

Nearly two decades later, the precise human toll of these
marketing decisions is difficult, if not impossible, to
document. Many patient records are now unavailable, and
because an AIDS test was not developed until later in the
epidemic, it is difficult to pinpoint when foreign
hemophiliacs were infected with H.I.V. - before Cutter
began selling its safer medicine or afterward. 

But in Hong Kong and Taiwan alone, more than 100
hemophiliacs got H.I.V. after using Cutter's old medicine,
according to records and interviews. Many have since died.
Cutter also continued to sell the older product after
February 1984 in Malaysia, Singapore, Indonesia, Japan and
Argentina, records show. The Cutter documents, which were
produced in connection with lawsuits filed by American
hemophiliacs, went largely unnoticed until The Times began
asking about them. 

"These are the most incriminating internal pharmaceutical
industry documents I have ever seen," said Dr. Sidney M.
Wolfe, who as director of the Public Citizen Health
Research Group has been investigating the industry's
practices for three decades. 

Bayer officials, responding on behalf of Cutter and its
president at the time, Jack Ryan, declined to be
interviewed but did answer written questions. In a
statement, Bayer said that Cutter had "behaved responsibly,
ethically and humanely" in selling the old product
overseas. 

Cutter had continued to sell the old medicine, the
statement said, because some customers doubted the new
drug's effectiveness, and because some countries were slow
to approve its sale. The company also said that a shortage
of plasma, used to make the medicine, had kept Cutter from
manufacturing more of the new product. 

"Decisions made nearly two decades ago were based on the
best scientific information of the time and were consistent
with the regulations in place," the statement said. 

The medicine, called Factor VIII concentrate, essentially
provides the missing ingredient without which hemophiliacs'
blood cannot clot. By injecting themselves with it,
hemophiliacs can stop bleeding or prevent bleeds from
starting; some use it as many as three times a week. It has
helped hemophiliacs lead normal lives. 

But in the early years of the AIDS epidemic, it became a
killer. The medicine was made using pools of plasma from
10,000 or more donors, and since there was still no
screening test for the AIDS virus, it carried a high risk
of passing along the disease; even a tiny number of
H.I.V.-positive donors could contaminate an entire pool. 

In the United States, AIDS was passed on to thousands of
hemophiliacs, many of whom died, in one of the worst
drug-related medical disasters in history. While admitting
no wrongdoing, Bayer and three other companies that made
the concentrate have paid hemophiliacs about $600 million
to settle more than 15 years of lawsuits accusing them of
making a dangerous product. 

The Cutter documents - a few of them have surfaced in
recent years in television and newspaper reports about
Cutter's marketing practices - were gleaned from that
litigation. But because the documents did not relate
directly to the lawsuits, most went uninvestigated. 

The documents - internal memorandums, minutes of company
marketing meetings and telexes to foreign distributors -
reveal and chronicle Cutter's decision to keep exporting
the older product after it began making the new one, which
was heat-treated to kill H.I.V., rendering the virus
"undetectable" in the product, according to a government
study. (There are few available records documenting the
actions and decisions of the three other American-based
companies that also sold unheated concentrate after
offering a heated product.) 

Doctors and patients contacted overseas said they had not
known of the contents of the Cutter documents. Bayer and
other blood-product companies, though admitting no
wrongdoing, have already made some payments to foreign
hemophiliacs. It is unclear if Bayer could now face legal
liability specifically for selling the older product after
a safer one was available. 

Federal regulators helped keep the overseas sales out of
the public eye, the documents indicate. In May of 1985,
believing that the companies had broken a voluntary
agreement to withdraw the old medicine from the market, the
Food and Drug Administration's regulator of blood products,
Dr. Harry M. Meyer Jr., summoned officials of the companies
to a meeting and ordered them to comply. 

"It was unacceptable for them to ship that material
overseas," Dr. Meyer said later in legal papers. 

Even so, Dr. Meyer asked that the issue be "quietly solved
without alerting the Congress, the medical community and
the public," according to Cutter's account of the 1985
meeting. Dr. Meyer said later that he could not recall
making that statement, but another blood-product company's
summary of the meeting also noted that the F.D.A. wanted
the matter settled "quickly and quietly." Dr. Meyer died in
2001. 

Whether Cutter was behaving ethically became an issue in
internal company discussions. "Can we in good faith
continue to ship nonheat-treated coagulation products to
Japan?" a company task force asked in February 1985,
fearing that some of its plasma donors might be H.I.V.
positive. The decision, records show, was yes. 

Taken together, the documents provide an inside view of
Cutter's bottom-line strategizing and efforts to manage the
flow of information amid growing public anxiety about the
safety of its product. 

When a Hong Kong distributor in late 1984 expressed an
interest in the new heat-treated product, the records show,
Cutter asked the distributor to "use up stocks" of the old
medicine before switching to its "safer, better" product.
Several months later, as hemophiliacs in Hong Kong began
testing positive for H.I.V., some local doctors questioned
whether Cutter was dumping "AIDS tainted" medicine into
less-developed countries. 

Still, Cutter assured the distributor that the unheated
product posed "no severe hazard" and was the "same fine
product we have supplied for years." 

Li Wei-chun said her son, who died in 1996 at the age of
23, was one of the hemophiliacs in Hong Kong who got AIDS
after using that product. 

"They did not care about the lives in Asia," Ms. Li said in
a recent interview. "It was racial discrimination." 

How It Started 
Discovery That Blood 
Spreads the Disease


At the beginning of the epidemic, more than two decades
ago, fear over what would later be known as AIDS was
centered mostly among gays and intravenous drug users. But
that changed on July 16, 1982, when the federal Centers for
Disease Control reported that three hemophiliacs had
acquired the disease. 

This gave epidemiologists a strong reason to believe that
the disease was being spread through blood products. And
that belief carried grave implications for the many
thousands of hemophiliacs who routinely injected themselves
with concentrate made from giant pools of donated plasma. 

Because an AIDS test had not yet been developed, federal
health officials had no idea how many plasma donors carried
the disease. 

By March of 1983, the C.D.C. went so far as to warn that
blood products "appear responsible for AIDS among
hemophilia patients." 

The unfolding story had not gone unnoticed at Cutter
headquarters. Back in January, Cutter's manager of plasma
procurement had acknowledged in a letter: "There is strong
evidence to suggest that AIDS is passed on to other people
through . . . plasma products." 

With sales of concentrate beginning to slip, Cutter got
more bad news in May 1983: after learning that a Cutter
competitor had begun to make heated concentrate, French
authorities decided to halt all imports of clotting
concentrate until they could figure out what to do. 

Fearing a loss of customers, Cutter conceived a marketing
plan that stopped well short of full disclosure. "We want
to give the impression that we are continuously improving
our product without telling them we expect soon to also
have a heat-treated" concentrate, an internal memorandum
explained. 

Several weeks later, Cutter tried to minimize the danger
hemophiliacs faced when using blood products. "AIDS has
become the center of irrational response in many
countries," the company said in a June 1983 letter to
distributors in France and 20 other countries. "This is of
particular concern to us because of unsubstantiated
speculations that this syndrome may be transmitted by
certain blood products." 

The French decided to keep using unheated concentrate, and
Cutter said it sold them more of the unheated product in
August 1983. Later, two French health officials were sent
to prison for continuing to use up old stocks of unheated
concentrate in 1985, when a heated product was available. 

Cutter finally received United States approval to sell
heated concentrate on Feb. 29, 1984, the last of the four
major blood product companies to do so. Though some doctors
and patients held out against the heated product, a safer
era had clearly begun for hemophiliacs in the United
States. 

Market Considerations 
Bayer Says Some 
Wanted Old Product 

For five months more, until August
1984, Cutter said it continued to make the old, unheated
medicine. The records suggest that the company hoped to
preserve the profit margin from "several large fixed-price
contracts." But in its statements to The Times, Bayer also
said that some customers still wanted the old medicine,
initially believing - incorrectly, it turned out - that
heating the concentrate could leave it less effective and
possibly dangerous. 

The new product, meanwhile, was selling briskly, leaving
Cutter with a problem: "There is excess nonheated
inventory," the company noted in minutes of a meeting on
Nov. 15, 1984. 

"They needed to get the return for what they invested,"
explained Michael Baum, a Los Angeles lawyer who has
represented dozens of United States hemophiliacs in suits
against blood-product companies. "They paid the donors.
They had processed the plasma, put it into vials, kept it
in warehouses - and all that expense had already been
incurred." (One vial is roughly equivalent to a small dose,
though more may be needed to stop severe bleeding.) 

At the November meeting, the minutes show, Cutter said it
planned to "review international markets again to determine
if more of this product can be sold." And in the months
that followed, it had some success, exporting more than 5
million units (a typical vial might contain 250 units) in
the first three months of 1985, documents show. 

"Argentina has been sold 300,000 units and will possibly
order more, and the Far East has ordered 400,000 units,"
according to a March 1985 Cutter report. Two months later,
the company reported that "in Taiwan, Singapore, Malaysia
and Indonesia, doctors are primarily dispensing nonheated
Cutter" concentrate. 

By then, while there were still a small number of buyers in
the United States, nearly all of the unheated concentrate
was being sold abroad, available records show. All told,
Cutter appears to have exported more than 100,000 vials of
unheated concentrate, worth more than $4 million, after it
began selling its safer product. 

Gary Mull, an international product manager for Cutter at
the time, said no one at the company had ordered him to
sell the unheated concentrate as a way of avoiding a
write-off. "If I had reason to personally believe, let
alone the company" that any of the material was highly
infectious, "we wouldn't have sent it out," he said. 

Mr. Mull, who now works for another blood-product company,
added, "I wasn't the shipping person, but I would still be
the person in charge of queueing it up." 

Bayer, which is based in Germany, said in its statement
that an overall plasma shortage in 1985 had kept Cutter
from making more heated medicine. But Cutter may actually
have contributed to that shortage - by using some its
limited plasma supplies to continue making the old product.


Bayer's response also emphasized that some countries were
slow to approve its new product. For example, Bayer said
"procedural requirements" imposed by Taiwan had delayed its
"ability to apply for registration" and had led to other
delays as well. 

But an official at Taiwan's health department, Hsu
Chien-wen, said recently that Cutter had not applied for
permission to sell the new, safer medicine until July 1985,
about a year and a half after it began doing so in the
United States. 

In one case, records show, Cutter officials even discussed
trying to delay Japan's approval of heated concentrate so
the company could shed stocks of the older product. Bayer
said Cutter did not act on that idea. 

Officials from the three other American-based companies
that continued to sell unheated concentrate - Armour
Pharmaceutical, Baxter International and Alpha Therapeutic
- either declined to be interviewed or denied wrongdoing,
in some cases citing the same reasons Bayer did for its
decisions. 

Still, what is not in dispute is that by the spring of
1985, few researchers doubted the connection between AIDS
and unheated concentrate. The previous October, the federal
Centers for Disease Control, using a prototype H.I.V. test,
had reported that 74 percent of hemophiliacs who used
unheated concentrate had tested positive for H.I.V. In the
same report, the agency said a study done with Cutter had
shown that heat treatment rendered the virus
"undetectable." 

(Bayer said no one knew "definitively" that its heat
treatment killed the AIDS virus until eight months later.) 

By May 1985, as the AIDS scare reached hemophiliacs in
Hong Kong, Cutter's distributor there placed an urgent call
to Cutter headquarters, records show. Sounding distraught,
he told of an impending medical emergency. Hemophiliacs
were frightened. Children were being infected with H.I.V.
Parents were hysterical. Couldn't the company send the new,
safer product? 

Cutter replied that most of the new medicine was going to
the United States and Europe, and that there was not enough
left for Hong Kong, though a small amount was available for
the "most vocal patients." 

Dr. Chan Tai-kwong, who treated hemophiliacs at Queen Mary
Hospital in Hong Kong, said doctors asked Cutter's
distributor for the heated concentrate but could not get
it; 40 percent of his patients were H.I.V.- positive, Dr.
Chan said. 

Dr. Patrick Yuen, who worked at another hospital, gave a
similar account. "The local distributor asked us to keep
using it," he said. "They said not to be afraid." 

Even so, Cutter knew the market for the older medicine had
all but dried up. 

"It appears there are no longer any markets in the Far East
where we can expect to sell substantial quantities of
nonheat-treated," a Cutter official wrote in May 1985.
Bayer said Cutter stopped shipping unheated concentrate in
July 1985. 

Later, in the early 1990's, two members of a Hong Kong
government commission that concluded the tragedy could not
have been avoided, expressed concern when told of the
internal Cutter documents. Dr. Yuen, a member of the panel,
said Cutter failed to warn doctors and hemophiliacs in Hong
Kong about the dangers of unheated concentrate. "It should
tell the whole world, not just Europe and America," he
said. 

Bayer also said Cutter did fully inform foreign customers
about the heated product. And Bayer said it took more than
a year to get Hong Kong's approval to sell it. 

But Dr. Cindy Lai, assistant director of Hong Kong's health
department, said that in the 1980's Cutter needed only to
get an import license. "It normally took one week," she
said. 

The delay harmed more than just the hemophiliacs, said Mrs.
Li, the mother of the young hemophiliac who died of AIDS in
1993. Infected with a terrible and still mysterious
disease, hemophiliacs were often shunned by family, friends
and employers. 

"It was the immoral drug company that caused some families
to fall apart," she said. "They blamed and tortured each
other. It was better to die than to live." 

The Message Gap 
Many Slow to Hear 
Of the Problems


Today, in the Internet age, vast amounts of the most
up-to-the-minute medical information are available to
almost anyone at the click of a mouse. News moved less
efficiently in 1985. 

In Taiwan, Dr. Shen Ming-ching, who ran the country's
largest clinic for hemophiliacs, recalled in a recent
interview that it was not until he traveled to the United
States for a conference in July 1985 that he learned for
certain that heat treatment killed H.I.V. Upon returning
home, he said, he immediately insisted that Taiwan
authorities stop importing the old concentrate. 

For his efforts on behalf of the hemophiliacs in Taiwan,
Dr. Shen said, the government gave him a certificate and "a
beautiful medal." As for the hemophiliacs themselves, 44 of
Dr. Shen's patients got AIDS, including a 2-year-old. He
said 23 had died. 

None of the Taiwan patients interviewed by The Times said
they knew that Cutter had begun selling the safer medicine
in the United States in early 1984. 

One Taiwan patient who received Cutter's old concentrate
was Lee Ching-chang, son of a rice farmer. Mr. Lee said he
got his first concentrate in November 1983 at age 22, and
continued receiving the unheated concentrate well into
1985. 

Mr. Lee said he tested positive for H.I.V. in 1986. "I am
bitterly angry," he said. Mr. Lee said he was too sick to
work. 

Six other hemophiliacs with H.I.V. or their families spoke
to The Times about despair, discrimination, job loss or in
some cases thoughts of suicide. Mr. Lee was the only
hemophiliac with H.I.V. willing to be photographed. 

Tang Fu-kuo helps AIDS patients in Taiwan. "I cannot tell
myself that it's just history; let's forget it," Mr. Tang
said. "Nobody wants to acknowledge fault." 

http://www.nytimes.com/2003/05/22/business/22BLOO.html?ex=1054568956&ei=1&en=58e3d9158742000e


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