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12:00 AM
Nov 16, 2009
 |  BioCentury  |  Strategy

Allston, we have a problem

Efforts by Genzyme Corp. to move past the manufacturing problems at its Allston, Mass. facility hit another stumbling block last week as FDA issued a warning letter about foreign particle contamination in five of Genzyme's marketed drugs.

In the notice to healthcare professionals, the agency said it was alerted to the particles, which are believed to be in less than 1% of products, through product quality reports submitted by Genzyme in May.

The foreign particles include stainless steel fragments, non-latex rubber from the vial stopper and fiber-like material from the manufacturing process in five Genzyme drugs: Cerezyme imiglucerase for Gaucher's disease; Fabrazyme agalsidase beta for Fabry's disease; Myozyme alglucosidase alpha for Pompe's disease; Aldurazyme laronidase for mucopolysaccharidosis type I (MPS I); and Thyrogen thyrotropin alpha for thyroid cancer.

The FDA warning is just the latest in a series of manufacturing missteps that have plagued the biotech and left some patients and physicians in the lurch.

Some Gaucher's patients, for example, have been put on reduced doses of Cerezyme to cope with the drug's shortage related to a viral infection discovered at the plant in June.

The prolonged shortage has spurred public health agencies and clinician groups to turn to yet unapproved products. In the process, they are conducting what amounts to a public experiment in reducing the maintenance dose of Cerezyme for Gaucher's patients.

Patients and doctors also will be deciding whether to convert to yet unapproved treatment being made available during the shortage, which means they will have to decide whether to switch back to the Genzyme product.

Additionally, Genzyme has faced issues over a lack of consistency in the products produced in different Myozyme bioreactors, which has resulted in delayed approval for larger batches of the drug, leaving some Pompe's patients untreated.

Foreign material

In a statement last week, Genzyme said "the safety profile of these products remains unchanged. A review of the global safety database for these products has not identified any safety concerns to suggest that patients treated with Genzyme products have been exposed to foreign particles. However, a theoretical safety risk remains should a particle enter a bloodstream."

The biotech also issued "Dear Health Care Practitioner" letters, cautioning physicians to check the vials for foreign material prior to administration and to monitor patients for infusion reactions.

Rather than pull the products from the market, FDA issued similar advice that doctors inspect each vial for foreign materials and monitor patients.

In its warning, the agency stated that it was "acutely aware of the critical need for patients to have continued access to these important products." The agency added that it considered the lack of FDA-approved alternatives for Fabrazyme, Cerezyme, Myozyme and Aldurazyme in its decision to allow the affected batches to continue to be marketed.

There are about 2,000 Gaucher's patients in the U.S., while the prevalence of Fabry's disease in the U.S. is 1 in 117,000 people.

The incidence of Pompe's disease is 1 in 40,000, with 5,000-10,000 adults living with the disease worldwide. MPS I occurs at a frequency of 1 in 100,000 to 1 in 500,000.

The Allston facility is responsible for the manufacture of Myozyme, Cerezyme and Fabrazyme, plus finishing work for all five drugs. Finishing work includes filling the vials.

In a conference call last week, Jason Woo, associate director for medical and scientific affairs in FDA's Office of Compliance, said that based on information that is continuing to be gathered, the agency and Genzyme decided it was at a point where the contamination was "large enough to warrant that this information be provided to healthcare providers."

Woo said that the first incidence of viral contamination at the Allston facility occurred in November 2008, with a second incident in May. He would not discuss why changes weren't implemented in November.

In June, Genzyme stopped bulk production at the facility and said inventories for Cerezyme and Fabrazyme would not be sufficient to meet projected global demand.

While particulate matter in a drug usually leads to a voluntary recall by the manufacturer, Woo said "these...

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