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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