NEWS: Bad Medicine

[Guest guest]

Bad Medicine

Herper

The Internet is a marvelous mechanism for selling things--including

things that are either illegal or just plain dangerous.

The Internet is a marvelous mechanism for selling things--including

things that are either illegal or just plain dangerous.

The Drug Enforcement Administration called it Operation Cyber Chase.

Between Apr. 18 and Apr. 20 federal agents made 20 arrests in five

states, Costa Rica and three cities in India. Investigators allege that

two Indian nationals, Brij Bhusan Bansal and Akhil Bansal, were running

an international operation that sold repackaged anabolic steroids,

narcotics and amphetamines made in India and other countries to

Americans over the Web. Since 2003, investigators say, the Bansals'

organization had been selling 2.5 million doses per month of drugs like

Vicodin.

The officials who busted this ring, which used e-mail spam to sell

drugs, say the Bansals are only the beginning. There are tens of

thousands of Web sites that sell prescription drugs of unknown origin

to Americans illegally. " All you get is a plain brown envelope, " says

Kindler, Pfizer's vice chairman.

Regulators and drug industry executives are pulling their hair out

trying to stem a rising tide of fake or low-quality medicines being

sold online. A Web site based in Canada may get its products from India

or China, or may traffic in counterfeits. Earlier this year Pfizer

executives were alerted to a batch of fake Lipitor when five patients

saw their cholesterol skyrocket and to a counterfeit of the glaucoma

drug Xalatan that contained mainly the antiseptic boric acid.

But counterfeit operations are often small fly-by-night firms that

operate out of shacks. An even bigger threat may come from Asia, Africa

and Latin America, where relatively large drug firms make copycat pills

that are legal in their own countries but fail to meet the standards of

safety and efficacy that the U.S. applies to generic and branded drugs.

Last year drug giant Eli Lilly enlisted the National Association of

Boards of Pharmacy to take a look at Web sites that purported to sell

" generic " versions of Lilly drugs. When the NABP investigators ordered

Zyprexa, Lilly's top-selling antipsychotic, they got something called

Telorzan, packaged in a cheap-looking blue box. When they ordered

Evista, for osteoporosis, they received something called Fenilox.

Orders for Cialis came back as Regalis or simply " generic " Cialis.

These putative knockoffs, most produced in South and Central America,

were sent to the Food & Drug Administration for analysis. None of them

passed muster. Some Telorzan contained 17 times the level of impurities

that would be expected in U.S. Zyprexa pills. The Fenilox didn't

contain any active ingredient, meaning the drug wouldn't prevent bones

from weakening and breaking. Like the Telorzan, the knockoff Cialis

pills were rife with impurities, and the amount of active ingredient

varied wildly.

To McAvoy, Lilly's U.S. director of regulatory policy, the drugs

represented a familiar problem. For five years he served as Lilly's

lead lawyer in Latin America, trying to defend the company's drug

patents in countries that by and large do not respect intellectual

property. He made the argument that the knock-offs weren't merely

harming Lilly but could harm patients, too: Copycat pills coming from

Mexico, Brazil and Argentina were substandard, made without any of the

rigorous tests that ensure the safety of medicines in the U.S.

In the past McAvoy convinced Mexican regulators to keep a copy of

Evista, the osteoporosis drug, off the market by showing that it didn't

dissolve properly. A similar line of attack kept a copycat of Gemzar,

for cancer, off the Brazilian market. In that case the drug's molecular

structure didn't match up with the branded version, changing its

effectiveness. " Doesn't somebody in Mexico or Brazil deserve the same

assurance of quality as someone in the U.S. or Europe? " asks Grey F.

Warner, the senior vice president for Merck's human health division in

Latin America.

A similar investigation conducted by the FDA of drugs being sold on the

Internet echoed Lilly's results. Copies of Viagra and Lipitor, both

supposedly protected by worldwide patents, had 65% and 81%,

respectively, of the normal amount of active ingredient. Not a single

pill met U.S. manufacturing standards. The Ambien generics were as much

as two times too strong. " If an elderly person took that they might not

ever wake up again! " says Hubbard, the FDA's recently retired

head of policy and planning. A research paper by Merck and outside

researchers showed that copies of Fosamax being sold in Latin American

countries--in violation of Merck's patents--didn't dissolve properly.

Depending on the pill, it might not work or it would worsen the drug's

side effects, causing severe heartburn.

Large pharmaceutical companies have a vested interest in portraying

international generics as unsafe. It's a way for them to increase their

market share in developing nations and, more importantly, it works to

prevent cheaper drugs from being imported into lucrative North American

and European markets.

Until recently drugmakers have remained relatively quiet on the dangers

of Internet drugs and international knockoffs. Some feared raising the

issue would make all drugs seem dangerous. But as Internet sites

proliferate and lawmakers discuss importing cheaper drugs from Canada,

it's time to think about safety. " Mostly it's been a discussion of the

patients needing cheaper drugs and the large pharmaceutical companies

wanting to maintain their prices in the U.S., " says Byron Cryer, a

gastroenterologist at the University of Texas Southwestern Medical

School and one of the authors of the Fosamax paper. " But there is an

issue that has to be considered, and that is quality. "

In South America there are cases where bad drugs may have already

caused harm. In one incident widely reported in 2003 the imaging agent

Celobar (something injected into the bloodstream to provide an X-ray

contrast) was manufactured in a way that poisoned and killed at least a

dozen patients in Brazil. In another Brazilian case a doctor is suing

Ranbaxy because she says its version of Roche's acne medicine Accutane

caused her son to have a stroke. " I can't give my patients a medicine

if I don't trust the quality, " says Luiz Cesar Povoa, one of the

founders of Brazil's regulatory system.

The problem is that in Brazil the law effectively divides drugs into

three classes. First there are the branded medicines sold by big-name

firms. There are also generics, which have to be tested to make sure

levels of a drug are absorbed properly into the body--the same kind of

test used to ensure that generics in the U.S. are safe.

Then there is a third class, known as similares, medicines which,

drugmakers pledge, have the right amount of active ingredient but

aren't tested in the body. Similarescan vary wildly in quality.

Mexico's system historically has resembled Brazil's. In Argentina there

are only similares; there is no process for approving generics. Nigeria

has been plagued by a glut of substandard and counterfeit medicines.

India, famously, produces a flood of generic drugs that can vary in

quality.

Argentinean export records seem to show tens of thousands of doses of

drugs, including knockoffs of erythropoietin and the cancer drugs

Eloxatin and methotrexate, making their way from Argentina into Canada.

There the trail stops, according to Norman Inkster, a former head of

the Royal Canadian Mounted Police and president of Interpol who now

works for big drug firms and other large corporations. " The regulatory

authorities are really set up around the belief that people who are

distributing pharmaceutical products are people who are playing by the

rules, " Inkster says. " They're ill prepared, in my opinion, to deal

with manufacturers who are not. "

Regulators are hard pressed to say for sure what has come over the

border. " We don't have the resources to check every package that's

coming into the country, " says , head of enforcement for

regulatory affairs at the FDA.

May 9, 2005

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