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Friday, November 2, 2012

An Increase in Scrutiny for Generics (USA)


The Food and Drug Administration said it was looking more closely at the way generic companies made extended-release drugs after it found one such medicine failed to work as well as its brand-name counterpart. The finding is a rare departure for the agency, which for years has insisted that generic drugs are just as effective as their brand-name versions.

The drug, a 300-milligram dose of bupropion, was manufactured by Impax Laboratories and was intended to mimic the popular antidepressant, Wellbutrin XL. But soon after it was introduced in 2006, patients who switched to it from Wellbutrin began complaining that their depression had returned. Impax and Teva Pharmaceuticals, which marketed the drug, have stopped selling the 300-milligram dose.


Although regulators have said the episode appears to be limited to one dosage level of a single drug, an F.D.A. official said in October that the agency was now looking more closely at the techniques generic drug makers used to make the extended-release drugs. “This has actually prompted us to change our policy,” Dr. Gregory P. Geba, the director of the F.D.A.’s office of generic drugs, said in an interview.

Generic drugs now account for the overwhelming majority of medicines prescribed in the United States, and extended-release drugs are a rapidly growing segment of the generic market. But they can be tricky to make. While the active ingredient is the same as the brand-name version, the mechanism for gradually releasing the drug into a person’s body can vary. The unusual decision by the F.D.A. that a generic was not the equivalent of the brand has provided fodder to some longtime critics, who say the F.D.A. and generic drug companies have been reluctant to acknowledge that sometimes generics don’t work as well as the brand-name originals.

Others dismissed such arguments, saying the recent criticism is just the latest effort in a longstanding campaign to unfairly discredit generics. “I think there’s still a cloud hanging over generic drugs,” said Joe Graedon, a pharmacologist who runs a consumer Web site, the People's Pharmacy, which raised questions five years ago about Teva and Impax’s version of Wellbutrin XL. “This may be far more common than the F.D.A. had realized.”

Ralph G. Neas, president and chief executive of the Generic Pharmaceutical Association, the industry trade group, said in an e-mail that the “F.D.A.’s science surrounding the approval criteria for all drug products, including extended-release products, is well grounded and rigorous.” His group, he said, supports the agency’s “ongoing examination of current science, as well as embracing evolving scientific methods for all drug products.” The popularity of extended-release drugs has increased rapidly in the last decade or so. In 2001, 84 extended-release drugs were sold in the United States; by 2011, the number had grown to 120, according to IMS Health, a health care information company.

Patients like the drugs because they can take them less frequently. But developing a longer-acting version of a best-selling medicine is also a classic strategy to extend the time that a company can sell a drug exclusively. Besides patenting the drug itself, brand-name companies can also acquire a patent for the way the pill releases the drug. Those methods can include complex technologies that employ tiny pellets or special coatings or laser-cut holes. The patent for the method can often outlast the patent for the drug itself.

When a brand-name drug does lose its patent protection, generic companies often seek to make their own extended-release version, one that dissolves the drug at the same rate as the branded product, but does not infringe on the other company’s patent. Generic drugs must contain the same active ingredient as their brand-name counterparts, but can differ in other ways, such as the pill’s inert ingredients and its size, shape and color. But some critics say the generic companies don’t always succeed at mimicking the longer-acting effects of the brands, and the F.D.A. does not do a good enough job of evaluating them. “I tell my patients I’m not against generic drugs, but I tell them that if they’re stable in whatever they’re taking, don’t let the pharmacy change them,” said Dr. Harry M. Lever, a cardiologist at the Cleveland Clinic. He said patients had complained for years about problems when they switched between generic brands, or from brand-name drugs to generics. Often those drugs are extended-release versions, he said.

Complaints about the bupropion pill surfaced soon after the drug was approved in December 2006. Patients who took the 300-milligram dose claimed their depression returned after switching from Wellbutrin XL, which was sold by GlaxoSmithKline. The F.D.A. had approved the 300-milligram dose without requiring a direct study in patients. Instead, it extrapolated from the results from an earlier study of a 150-milligram dose. Impax and Teva’s 150-milligram dose remains on the market.

The F.D.A. and representatives for Impax and Teva declined to comment on the mechanism used in the extended-release bupropion tablets or why it didn’t work well in the 300-milligram dose, saying it was a trade secret. The agency initially dismissed the patients’ concerns, saying the symptoms were likely because of the “natural course” of depression and not a failure of the drug. Still, it asked Teva and Impax to conduct a study of people who used the higher dose and had complained of problems. But the companies canceled the study in late 2011, saying they couldn’t recruit enough participants.

In 2010, the F.D.A. took the rare step of conducting its own study of the 300-milligram strength. In early October, it announced that the drug did not, in fact,  perform as well as the brand. Representatives for Teva and Impax declined to comment on whether they intended to sell the higher dose in the future. Dr. Geba said he wished the agency had uncovered the problem sooner, but the issue was clouded by the fact that depression is difficult to treat. “It’s understanding the adverse events — are they real or are they part of someone’s actual illness?” he said. “That’s not an easy thing to assess.”

Source: NY Times 

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