F.D.A. Again Warns a Generic Maker About Conditions at Its Plants

Posted on Apr 19, 2010 in Uncategorized



Jim Ross for The New York Times

A worker at Apotex in Toronto. The Canadian company was said to have $879 million in United States sales last year.

In the letter, posted on the Food and Drug Administration’s Web site late Wednesday, the agency cited lapses at Apotex, Canada’s biggest drug company, that included charred particles in a diabetes drug; contamination of an antihistamine, and drug cross-contamination that resulted from inadequate cleaning of manufacturing equipment.

The letter also said the company had failed to notify regulators in a timely fashion about such problems.

Apotex, with headquarters in Toronto, was the eighth-largest provider of generics in this country last year, with $879 million in American sales, according to IMS Health, an industry research firm that tracks drug sales. In 2009, American pharmacies filled 94 million prescriptions with Apotex medicines, IMS said.

Apotex did not respond to a phone message or e-mail request on Thursday seeking comment about the letter.

The F.D.A. action comes as another well-known generic maker, Ranbaxy, has also come under the agency’s spotlight for manufacturing and quality control problems at two of its factories in India and one in Gloversville, N.Y.

Those regulatory actions focus attention on generic quality at a time when Americans are increasingly turning to the medicines to save money on their prescription drugs. Generic drugs now account for 75 percent of the prescriptions filled in this country, according to the latest data from IMS.

Concerns about the quality and effectiveness of generics have become prevalent enough among doctors and patients that the F.D.A. held a public advisory meeting this week to discuss the issue and explore whether additional regulation of the drugs would increase public confidence in the products.

But in an interview last month, Gary J. Buehler, an F.D.A. official and former director of the agency’s office of generic drugs, said that the F.D.A. ensured that generic makers adhere to proper manufacturing standards and produce high-quality products.

“Generic quality is good,” Mr. Buehler said.

He added that people should not judge the entire generic industry by a few isolated incidents.

Indeed, the F.D.A. has periodically accused brand-name drug makers and generic makers of violating manufacturing or quality control standards. Typically, the companies have put the matters to rest by quickly correcting the problems to the agency’s satisfaction.

The new F.D.A. letter is unusual because it is the second warning to Apotex in less than a year. The current letter, dated March 29, cites problems found at an Apotex factory in Toronto during an inspection last summer.

Last June, the agency warned Apotex about similar issues arising from an earlier F.D.A. inspection of another facility in Etobicoke, Ontario, in late 2008.

Taken together, the violations “demonstrated a lack of adequate process controls and raised serious questions regarding your corporation’s quality and production systems,” agency officials wrote to Jack M. Kay, the president and chief operating officer of Apotex, in the March 29 letter.

“This warning letter is being issued because of serious and repeat violations from the 2008 and 2009 inspections and because your response,” the agency wrote, “is inadequate and lacks sufficient corrective actions.”

Since last August, the agency has prohibited drugs from the Etobicoke and Toronto sites from entering the United States, although Apotex has other plants it can ship from.

From July 2007 to August 2009, Apotex voluntarily recalled all products associated with manufacturing concerns — about 659 batches of various drugs — in the United States, the F.D.A. said.

Many Americans first heard the name Apotex in 2006 when the company briefly flooded the United States market with a generic substitute for the blood thinner Plavix before the name-brand drug’s main patent had officially expired.

A federal judge later blocked Apotex from selling the generic until a court could rule on the patent’s validity. The patent holders, Bristol-Myers Squibb and Sanofi-Aventis, eventually won on appeal.

Apotex produces more than 300 kinds of generic drugs in about 4, 000 dosages and formats, according to the company’s Web site. Apotex, which is privately held, has annual revenue of more than $1 billion Canadian, the Web site said.

In a statement last September, Apotex said that the F.D.A.’s import ban applied to only two of the company’s many factories and that the company was working with agency officials to resolve their concerns.

“We pride ourselves on being a leading maker of top-quality generic pharmaceuticals,” Mr. Kay, the Apotex executive, said in the September statement.

But the F.D.A.’s recent letter said officials remained concerned about continuing manufacturing issues at Apotex.

Until Apotex corrects the problems to the agency’s satisfaction, regulators will recommend that the F.D.A. withhold approval for any new products listing Apotex as the manufacturer, the letter said.

A version of this article appeared in print on April 16, 2010, on page B6 of the New York edition.