More contamination troubles for Genzyme

Federal regulators yesterday warned doctors to look for foreign particles in five Genzyme drugs used to treat rare genetic disorders, including two - Cerezyme and Fabrazyme - that have been rationed because of the viral contamination detected in the Allston Landing plant last summer. The five drugs represent roughly half of Genzyme’s $4.6 billion in annual sales.

The diseases treated by these enzyme replacement drugs are rare. About 5,500 people worldwide, for example, depend on Ce rezyme, the best-selling Genzyme drug, while about 2,500 use Fabrazyme. Cerezyme treats Gaucher disease, which causes fatty substances to accumulate in the liver, spleen, and other organs. Fabrazyme treats Fabry disease, which prevents the body from breaking down oils and fats that build up in the eyes and kidneys.

Particles are believed to have been found in less than 1 percent of the Genzyme drugs based on product lots examined, according to a statement from the Food and Drug Administration. The FDA warned physicians, however, to carefully examine vials of the products and filter them before they are given to patients - steps that are considered standard procedure within the industry. If they find particles, the FDA asked for the vials to be returned to the manufacturer. The agency warned that ingesting the particles could have effects that include allergic reactions and blood clotting.

FDA inspectors arrived at the Allston plant last month to begin an investigation into Genzyme’s production operations.

“Based on information the agency has from Genzyme, we don’t believe this is a wide-scale problem,’’ said Dr. Jason Woo, associate director of medical affairs in the compliance office at the FDA’s research center in Silver Spring, Md. “But we do not have information that fully defines the scope of the problem.’’

In other circumstances, the FDA might have required Genzyme to recall drugs contaminated with particles, Woo said. But because the Cambridge company is the sole supplier of many of its products, the agency agreed the “orphan’’ drugs should be kept on the market with intensified production scrutiny, he said.

Patients who use Genzyme’s drugs have been carefully following its efforts to rebuild inventories after last summer’s highly publicized plant shutdown and the viral decontamination that followed, but some were caught by surprise by yesterday’s development. Linda Rubenstein, a Gaucher disease patient in Carlisle, said she hadn’t heard about the new contamination. Rubenstein hasn’t received a Cerezyme injection since July because of rationing and doesn’t expect to get one for several months. She has not experienced a return of symptoms.

“It’s frustrating having to wait and not get the Cerezyme,’’ she said, “but I think Genzyme has done a good job about keeping us informed.’’

Rubenstein said she would withhold her opinion about the new setback until she could learn more about it.

The information that sparked the FDA’s warning to doctors was based on reports filed by Genzyme. The company sent a letter to health care practitioners Wednesday, recommending precautions similar to those outlined by the FDA. The letter, posted on the company’s website yesterday, noted that the problem was unrelated to this summer’s viral decontamination in Allston.

In the letter, Genzyme said it has reviewed a database of problems with its products in recent years. “This review has not identified any safety concerns to suggest that patients treated with Genzyme products have been exposed to foreign particles,’’ the letter said.

Geoff McDonough, senior vice president and general manager for genetic diseases at Genzyme, said particles are an issue for all biotechnology manufacturers.

There are moving parts in the company’s production machinery, and workers wear sterile gowns in the “finishing’’ labs where Genzyme workers fill vials for shipment to health care providers, McDonough said. “Those moving parts and sterile gowns can shed microscopic fibers or pieces of stainless steel that get into the vials,’’ he said. “We look at every vial as part of our finishing process. We remove the vials that have particles found in them, and we throw them out.’’

For the past three weeks, the FDA has been conducting an investigation at Genzyme’s Allston Landing plant on the Charles River. Agency officials wouldn’t comment on that inquiry, and didn’t say why they chose yesterday to issue the advisory on the particle contamination.

The FDA has monitored efforts to combat such contamination at Genzyme and other companies for years, but has become more sensitive to the issue recently, as biotech companies have tried to agree on standards for particle inspections. Earlier this week, under FDA scrutiny, drug maker Hospira Inc. of Lake Forest, Ill., recalled dietary supplement and anesthesia products because of contamination.

The level of contamination cited in yesterday’s FDA warning is not unusual, McDonough said. Particles are generally found in about 1 in 100 vials, or 1 percent of the product before it leaves the plant, he said.

McDonough said a smaller fraction of vials with particle contamination, about 0.02 percent, are discovered by health care practitioners and returned to Genzyme. “Based on the information publicly available, we think our rates are within the industry experience,’’ McDonough said. “But the FDA has clearly asked us to focus on doing things better, and we’re focused on that.’’

Shares of Genzyme yesterday plunged 7.3 percent, a loss of $3.89, to $49.28 on the Nasdaq stock exchange, their biggest drop since February, as investors absorbed the news of the latest setback.

Industry analysts said Genzyme has been working hard to restore its credibility at a time when regulators have allowed a pair of competitors, Irish drug maker Shire PLC and Israeli start-up Protalix Biotherapeutics, to expand use of rival treatments to Cerezyme in the clinical trials necessary before those drugs are approved for commercial use.

“This is a new contamination issue that Genzyme has to deal with,’’ said John L. Sullivan, research director for Leerink Swann, a Boston investment bank specializing in health care and life sciences. “They should still be able to resolve this and put the issue behind them.’’

In addition to Cerezyme and Fabrazyme, the drugs covered in the FDA’s warning are Myozyme, which treats Pompe disease, a muscular disorder; Aldurazyme, which treats mucopolysaccharidosis, a metabolic disorder; and Thyrogen, which treats thyroid cancer. Cerezyme and Fabrazyme are manufactured in Allston, while Myozyme and Thyrogen are produced in Framingham and sent to Allston for finishing. Production of Aldurazyme, which formerly was made in Allston, was shifted to a Genzyme partner in California about 18 months ago. It was covered in the FDA advisory because vials filled in Allston remain in the inventories of health care providers.

Robert Weisman can be reached at weisman@globe.com.