Generic drugs are trickier than they look. Go back about 50 years and it was generally assumed that if you had the same amount of active drug, and the tablet broke up in the stomach within a specified time limit, you had a good generic drug that was fit to use in place of the original drug. It made perfect sense at the time. That stopped in the mid 1960s when Gerhard Levy of SUNY Buffalo and John Wagner of the University of Michigan found that the existing tests didn’t necessarily translate into the same blood levels as the original product. That means the same amount of drug in the blood stream at the same time after taking a dose. Getting a new formulation to match up with the original can be difficult.
Generic drugs are big business. The Drug Price Competition and Patent Term Restoration Act, also known as the Hatch-Waxman Act of 1984 encouraged the use of generic drugs and created the current system for FDA evaluation of generics. Most states have laws either mandating or limiting generic substitution. In some states, the pharmacist must dispense a generic whenever one is available unless the prescriber insists that the branded product is medically necessary. In other states, there are individual drugs, or classes of drugs, that should not be substituted. Typical classes of drugs that are exempted from generic substitution include thyroid medications, anti-epileptics, anticoagulants, and lithium. Most of these do-not-substitute lists make sense, with just a touch of lobbying – these are classes of drugs where the dosing has to be very precise and even the normally accepted variations in blood levels might cause problems. Even so, an estimated 84% of all prescriptions in the United States are filled with generic drugs. Generics may cost a small fraction of the price of the branded products, and generic substitution may save money not only for the patient, but for the government paying for drugs in public hospitals and clinics. According to IMS Institute for Healthcare Informatics, the United States spent $325.8 billion on medications in 2012, an average of $898 per person. Obviously, most of this went to generic companies. Their profit margins may be small, but the total amount of money involved is very large.
While the FDA has insisted that generic drugs are the equal of their branded competitors, there is some history of generic manufacturers faking the results of the tests needed to obtain marketing approval. In the 1980s, Bolar Pharmaceuticals was found to be disguising the branded product to look like the Bolar version, then submitting the faked version for testing. The New York Times report on the House of Representatives hearings quoted one committee member: photographs ‘’where it appeared that Bolar had actually rubbed the original firm’s logo off the pill. You could see the outline of the logo and the pill was slightly smaller in size, indicating it had been sanded down. Their explanation was that it was a mistaken batch, but they did it in three different batches.’’ The Baltimore Sun reported “Triamterene/Hydrochlorothiazide, a generic brand of the anti-hypertensive drug Dyazide, was approved in April 1987 by the FDA and generated $140 million in revenue for Bolar before it was recalled in February 1990.” Other generic manufacturers were found to be doing the same things, and several companies were making payoffs to FDA officials to speed up approval of their products.
This year, the focus has been on Ranbaxy, the Indian generic giant. Some Ranbaxy products have been banned from import due to reports of violations of standards of good manufacturing practices, but violations GMP, however bad are probably inadvertent. But in Ranbaxy’s case, they were reported to be submitting bioequivalence reports for which no tests had been done. No tests had been done – they just wrote down numbers that were as imaginary as the square root of -1. They hadn’t even taken the trouble to submit false samples.
The FDA has been accenting plant inspections since 2009, but tight budgets limit the agency’s ability to visit plants as often as would be desirable, particularly plants located overseas, and 40% of generic drugs sold in the US are produced overseas, including in China and India. Also, 35% of the FDA budget comes from “user fees”, money paid by drug companies for prompt review of New Drug Applications. The FDA has already been accused of focusing on these NDA applications to avoid losing the fees, and that means diverting staff from other activities, including plant inspections. In 2010 the US General Accountability Office issued a report saying the FDA was not conducting nearly enough foreign inspections, this in spite of the fact that the Obama administration had budgeted $41 million for foreign plant inspections, up from the $12 million in the last Bush budget.
The shutdown showed us some of the things we buy with our tax payments and why we need government. Bolar and Ranbaxy showed us another. Now can we discuss drowning government in the bathtub?
Sam Uretsky is a writer and pharmacist living on Long Island, N.Y. Email email@example.com.
From The Progressive Populist, December 15, 2013
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