Puerto Rico factories linked to tainted drugs

SAN JUAN, Puerto Rico - The first warning sign came when a sharp-eyed worker sorting pills noticed that the odd blue flecks dotting the finished drug capsules matched the paint on the factory doors.

After the flecks were spotted again on the capsules, a blood-pressure medication called Diltiazem, the plant began placing covers over drugs in carts in its manufacturing areas.

But the factory owner, the Canadian drugmaker Biovail Corp., never tried to find out whether past shipments were contaminated - or prevent future contamination, according to U.S. regulators.

Thirteen of the 20 best-selling drugs in the United States come from plants on this island. An investigation by the Associated Press found dozens of examples over four years of lapses in quality control in the Puerto Rican pharmaceutical industry, which churns out $35 billion of drugs a year, most of it for sale as part of the $300 billion market in the United States.

A review of 100 pages of Food and Drug Administration reports shows even modern drug plants here that are under the watch of U.S. regulators have failed to keep labs sterile and have exported tainted pills.

"The common denominator of all these is there's really poor quality control," said Sidney Wolfe of the watchdog group Public Citizen.

FDA officials say the problems in Puerto Rico are proportionate with the large number of drug plants here and generally no worse than those on the mainland.

Consumer advocates say they demonstrate the agency does not sufficiently monitor the industry anywhere.

The FDA issued a warning letter to Wyeth in May 2006, after consumers reported finding machinery pins inside bottles of Effexor, a leading antidepressant, and the heartburn drug Protonix. The letter expressed concern that the plant was not "able to detect that the affected equipment was missing some of its parts." The company, based in Madison, N.J., faulted mistakes by workers who packaged the drugs.

In another case cited in a June 2006 FDA inspection report, a plant owned by Teva Pharmaceutical Industries exported drugs - including the diabetes treatment Metformin - even though they were known to contain small amounts of metal particles. The Israeli company had also received at least six consumer complaints of dark residue inside bottles or foreign material embedded in tablets, according to the report.

Teva's quality-control unit said the presence of some metallic material was to be expected because the manufacturing equipment is made of metal, the report said.

Teva recalled 21 different drugs as a result of the inspection, FDA officials said; two months later the company announced it was closing the plant, citing a restructuring.

Denise Bradley, a Teva spokeswoman, said the medicine from the now-closed plant was still safe and effective.

The reports obtained by AP were produced by FDA inspections from 2003 to 2007 of 13 pharmaceutical plants - roughly half the total in this U.S. territory, a Caribbean island with one of the world's highest concentrations of drugmakers.

Several are closing or downsizing as the expense of updating old plants to meet regulations adds to struggles with rising energy costs and tightening tax breaks.

The FDA often hesitates to crack down at the first sign of problems because manufacturers can chalk them up to isolated problems, said John Scharmann, a former FDA administrator for the Denver district who is now associated with a watchdog group.

That appeared to be the case at the Biovail-owned factory in the San Juan suburb of Carolina where a sharp-eyed worker noticed the foreign specks of blue.

"Incident was considered an isolated event . . . even when the employee reported having observed the same particles before," the report said.

David Elder, director of enforcement in the FDA's regulatory affairs office, said drugmakers usually fix problems on their own and issue needed recalls once notified.

"They're making products that save or support lives, so it's not in their interest to make products that are unsafe or ineffective," he said. "They're good corporate citizens by and large and want to do right by their patients."

Four of the plants described in the reports closed or announced plans to do so after discovery of significant quality-control problems, but none cited the discoveries as a reason for closing.

Some plants in Puerto Rico are three decades old, built when the territory's pharmaceutical industry took off thanks to tax incentives aimed at developing more high-tech manufacturing. The industry here has faded somewhat since.

Still, this island turns out some top-selling drugs on the U.S. market, including the cholesterol drugs Lipitor and Zocor, the blood-thinner Plavix, anemia drugs Aranesp and Epogen, and the antidepressant Zoloft.