Contaminants Found in Some Genzyme Product Lots

Kate Traynor

BETHESDA, MD 13 November 2009—Particulate contaminants including stainless steel fragments, rubber, and fibrous material have been discovered during quality testing of five injectable products manufactured by Genzyme, FDA announced today.

The affected products are the enzyme-replacement therapies imiglucerase, agalsidase beta, alglucosidase alpha, and laronidase, along with Thyrogen, the company's thyrotropin alfa product.

The contaminants are believed to be present in less than 1% of affected lots, all of which begin with the letter A, according to FDA. The agency is "actively investigating the nature of the contamination and seeking immediate implementation of corrective actions to mitigate the situation," according to the announcement.

FDA is allowing the products to remain on the market because there is a critical need for them in patients with certain rare diseases, and alternative FDA-approved therapies are unavailable or may be unsuitable for some patients.

Levothyroxine withdrawal may be an appropriate alternative to the use of thyrotropin alfa in some patients, according to FDA.

The agency stated that it is unaware of any adverse events in patients related to the administration of the contaminated Genzyme products. But localized adverse reactions to the particulates could potentially occur after i.m. injection, which is the recommended route of administration for Thyrogen.

The other products are delivered by i.v. infusion, and the presence of particulates could cause serious adverse events, including blood-vessel damage, embolism, and hyperimmune reactions, according to FDA.

The presence of the particulates may also affect the effectiveness of the products, the agency stated.

FDA has recommended that health care providers carefully inspect vials of the affected lots for the presence of particulates before reconstituting or preparing to administer the products. If particulates are found, the material should be returned unused to Genzyme (phone 800-745-4447 and select option 2).

FDA recommends the continued use of an inline, low-protein-binding 0.2- or 0.22-micrometer filter during the administration of the enzyme-replacement therapies. But the agency has not determined whether such filtration will remove all of the particulates.

Patients should be monitored for the development of local or systemic infusion reactions after the infusion, FDA stated.

Earlier this year, Genzyme closed down the facility where the particulate-contaminated products were manufactured in order to eradicate a viral contaminant found in a bioreactor. The shutdown resulted in shortages of imiglucerase and alglucosidase alpha. In financial documents released this month covering the quarter ending September 30, the company stated that the plant had been sanitized and was undergoing FDA inspection.

According to FDA, the agency learned of the particulate-contaminated vials from product quality reports, which manufacturers are required to submit to the agency to comply with Current Good Manufacturing Practices.