PFPC Daily - March 4, 2005

FDA seizes medications at 2 facilities

Boston Globe - March 5, 2005

By Christopher Rowland

Federal regulators conducted highly unusual raids yesterday at
GlaxoSmithKline Inc. facilities in Puerto Rico and Tennessee and
seized large supplies of two of the pharmaceutical company's
prescription drugs, the antidepressant Paxil CR and the diabetes drug
Avandamet.

The Food and Drug Administration, which worked with the Department of
Justice and the US Marshals Service on the seizures, cited
manufacturing problems at a GlaxoSmithKline plant in Puerto Rico that
resulted in substandard pills reaching the market.

FDA seizures from major pharmaceutical companies are rare, former FDA
officials said. In this case, the agency said it took the dramatic
step because GlaxoSmithKline had repeatedly failed to correct
problems at its Cidra, Puerto Rico, factory that were first
identified
in 2002.

''FDA and the Department of Justice will not allow drug manufacturers
to ignore our high public health standards for drug manufacturing,"
said John M. Taylor, FDA associate commissioner for regulatory
affairs, in a statement.

The drugs did not pose a significant health hazard in either case but
still presented ''potential risk to consumers," the agency said.

In the case of Paxil CR, a 24-hour-release version of its big-selling
antidepressant, the pills sometimes split apart and a patient could
take a portion of a tablet that contains either no active ingredient
or no timed-release ingredient. The result would be similar to
missing a dose or getting two doses at once.

The FDA said some Avandamet tablets did not contain accurate doses of
the active ingredient. GlaxoSmithKline said some batches of Avandamet
-- a combination pill of two diabetes drugs, Avandia and metformin --
contained too much of Avandia's main ingredient.

The FDA and the company said patients on these drugs can safely take
remaining tablets in their medicine cabinets but warned of expected
disruptions in supply. Patients should consult with their doctors
about finding alternative treatments, which physicians said are
readily available.

Neither the government nor the firm disclosed how many drugs agents
seized. GlaxoSmithKline recalled some batches of both drugs in a
limited action in February, but the FDA said it did not recover all
of the problem tablets.

The morning seizures at a manufacturing facility in Puerto Rico and a
Knoxville, Tenn., distribution facility did not apply to supplies in
pharmacies around the country, and there was no general recall.

CVS Inc., the nation's largest retail pharmacy chain by number of
stores, said it was advising customers that the FDA said it was safe
to keep taking the pills.

''We are continuing to dispense what we have on our shelves," said
CVS spokesman Todd Andrews.

A 2002 FDA warning letter following inspections at the plant cited
poor quality control, review procedures, and decision making by plant
managers. A former FDA official, James Farley, who is now principal
of Cardinal Consulting and Training, in St. David's, Pa., said the
language in the 2002 warning letter indicated significant problems at
the plant.

''FDA believes there is something seriously wrong with their quality
system," Farley said. ''It is surprising GlaxoSmithKline would have a
seizure. The cases where I have seen it occur were borderline firms."

GlaxoSmithKline, based in Great Britain with US headquarters in
Philadelphia, is the world's second-largest drug company. It sold
$725 million worth of Paxil CR in 2004 and about $500 million worth
of Avandamet.

The company's stock fell 3.1 percent yesterday, to $48.91.

The company began inspecting each Paxil CR pill in November 2004 to
weed out any split tablets, GlaxoSmithKline spokeswoman Nancy Pekarek
said. It has also developed a solution to prevent excess active
ingredient from getting into its Avandamet tablets; the problem
occurred in a combination dose that included 1 mg of Avandia and 500
mg of metformin, she said.

The firm brought both problems to the attention of the FDA and had
been keeping the agency abreast of progress, she said.

Physicians said the problems with pills cited by the FDA did not
appear dangerous for patients. Additionally, in both cases, when
patients' supplies run out they can switch to other prescriptions,
they said.

Depression sufferers on Paxil CR can switch to regular Paxil, which
comes in brand and generic forms, and adjust the dose to mimic the
24-hour release, said Dr. J. Alexander Bodkin, chief of clinical
psycopharmacology at McLean Hospital in Belmont.

Diabetes patients on Avandamet can switch to individual doses of
Avandia and metformin, which is what they took before Avandamet was
introduced in 2002, said Dr. David Nathan, director of the diabetes
center at Massachusetts General Hospital.

Nathan said he thought the FDA's statements about the health issues
associated with the seizures were confusing because they downplayed
dangers while emphasizing potential risks to patients.

He said the FDA's statements had about as much value as the orange
and yellow terror alert levels issued by the Department of Homeland
Security.

''That's bothersome. They should either say there is a problem or
not," said Nathan. ''They are obviously trying not to panic the
public."