Generic drugs have a dodgy past, medical historian says


Credit: Gary Neill

Jeremy A. Greene admits to a bias when he began researching the history of generic drugs for a book. He was a physician who regularly prescribed and took generic drugs. He gave them to his children and saw generics as a valuable alternative to expensive brand-name drugs. The book project began, Greene says, as a back door into "exposing the underbelly" of America's brand-name pharmaceutical companies. "I had thought that the generic drug industry had a moral gloss attached to it, that it was good and virtuous and part of a beneficial public-minded policy," he says.

Then Greene, a medical historian in the School of Medicine, got to the 1990s. The Food and Drug Administration approves new drugs only after clinical trials demonstrate their safety and efficacy. But a generic needs only to demonstrate its similarity to the drug that it is designed to mimic. Turns out, in the '90s, several generic firms supplied regulators with test samples of the actual brand-name drug instead of their generic. In one instance, a company simply sandpapered the pharmaceutical company's logo off a pill and submitted it as its own creation. In that instance, they did such a shoddy job they got caught. "Unfortunately for the generic firm," Greene writes in the book, "the pill artists ... hadn't fully removed all evidence of the logo."

Uncovering the sometimes-sordid past of the generic drug business "completely shocked me," Greene admits. On a sunny fall morning on the Homewood campus, he sits in the atrium of Gilman Hall and talks about the genesis of his book Generic: The Unbranding of Modern Medicine (Johns Hopkins University Press, 2014). "[For] a historian of science and technology and medicine, the question emerges: Why look at something so mundane?" Greene says. "It doesn't seem like an object that you would write a scientific history about." But it is generic drugs' very mundanity—their pervasiveness and tacit acceptance in daily life—that sparked Greene's interest. Here is an industry that barely existed 50 years ago. In 1960, fewer than 10 percent of drug prescriptions in America were for generics. By 2010, that number had jumped to 80 percent. Today, as patents for brand-name drugs expire— like the cholesterol-lowering Lipitor, the acid-reflux pill Nexium, and the blood thinner Plavix—the substitution of bioequivalent generic drugs for more expensive products has become a trillion-dollar industry.

Generics now save American consumers real money. In 2012, Americans spent less on prescription drugs for the first time in almost six decades, with generics reducing spending on medicine by $28.9 billion that year. "It's hard to find people who don't relate to this topic in some visceral way because most people have consumed a generic drug or know someone who has," Greene says. And as a historian, this is what gets him excited: the study of how scientific knowledge and governance impact the everyday reality of our lives.

Greene says his research challenged some of his assumptions. In making generics a safe and regulated alternative, the scientific and regulatory community initially believed that it was only the drug itself that mattered. Turns out that assumption is erroneous. Greene tracks the rise of what is now called the science of similarity in the late 20th century, which discovered that a drug's efficacy is never just about the molecule. While patents may expire—opening up competition by generic companies to replicate the drug's basic chemical composition—trademarks last, meaning a generic company may not legally create a pill that is 100 percent like its brand-name predecessor.

So a generic is similar but not exactly the same as its counterpart. And some of the differences can affect a drug's efficacy. "You could have the molecule present in the pill, but if the layer of shellac on the surface of the pill was too thick, and someone swallowed the pill and it came out the other end not being absorbed, well, then, the shellac mattered." It is, in other words, not just the chemical composition of the drug but also the way a pill is produced, how it is pressed and bound in manufacturing, and how the human body absorbs it. There can even be a negative effect when patients presume that a generic will not be as effective. "What were thought to be incidental, inactive parts of the drug could matter," Greene says.

Greene chronicles a geopolitical debate surrounding the nature of generics. On one side of the argument, you have generic companies that claim their product is the same in every way except appearance and price. On the other, you have pharmaceutical companies claiming that generics are inferior. (Lest you think the scandal and graft were all on the part of generic manufacturers, Greene recounts the tale of a researcher hired by a pharmaceutical company to prove that generic competitors were substandard. When her research proved otherwise, the company quashed the results.) This global debate over generics is far from resolved. "The French government still rejects the notion that a generic drug can be considered equal to a brand-name drug," Greene says. But in a country where socialized medicine allows the government to negotiate drug prices, brand names often cost the same as a generic.

Not so in America. The history of generics in the United States, which is the focus of Greene's book, is largely about economics. The federal government cannot legally negotiate lower prices for prescription drugs, not even through Medicare. So generics have emerged as a free-market solution to the issue of affordable health care. The result is that the generic pharmaceutical market exhibits all the foibles and irregularities of the marketplace. Greene points to the generic Doxycycline, a full-spectrum antibiotic created by Pfizer in the 1960s under the brand name Vibramycin, and capable of treating everything from Lyme disease to STDs. The generic went from being pennies a pill to more than $150 a dose when demand surged.

Greene's research takes in everything from the mom-and-pop operations of the mid-20th century to the multinational corporations of today, airing all the dirty laundry, politics, and controversy along the way. But his intent was not to discredit the industry. Generics, he points out, are a rare success story in a health care industry bloated by inefficiency and expense. "The question I tend to get from people around this topic is, 'As a physician, do you believe I can trust generic drugs?'" Greene says. "The short answer is, 'Yes. You can trust them.' My goal was not to make people distrust the system but to suggest
 that it helps to be conscious of those systems and to insist on as much transparency as possible."

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