FDA, Genzyme legal settlement may limit availability of thyrotropin alfa

Genzyme has signed a consent decree agreeing to correct manufacturing quality violations at its Allston, Mass., manufacturing facility and will turn over to the federal government $175 million in unlawful profits from the sale of products that were made at the plant, according to information from the FDA.

Genzyme is the sole supplier of several enzyme replacement drugs for injection that are used to treat rare genetic disorders. Products include thyrotropin alfa (Thyrogen), used to diagnose thyroid cancer; imiglucerase (Cerezyme), used to treat Gaucher’s disease; agalsidase beta (Fabrazyme), used to treat Fabry’s disease; and alglucosidase alfa (Myozyme), used to treat Pompe’s disease.

During an inspection of the Allston plant from Oct. 8 to Nov. 13, FDA inspectors found that the company’s systems for ensuring manufacturing quality were “inadequate,” resulting in production delays; critical shortages of medically necessary products to consumers; and drugs contaminated with metal, fiber, rubber and glass particles. Genzyme also temporarily suspended manufacturing of some products because of a viral contamination in a bioreactor that makes bulk amounts of its drugs, which ultimately resulted in additional drug shortages. These manufacturing problems violated the FDA’s regulations for manufacturing practice, according to an agency release.

Under the consent decree of permanent injunction, the Massachusetts-based company agreed to adhere to a strict timetable to bring the plant in line with the regulatory requirements of the FDA. The decree was filed in the U.S. District Court for the District of Massachusetts on May 24.

The FDA said it is working with Genzyme during the company’s remediation to ensure availability of the company’s medically necessary drugs.

“It is critical for the safety of the drug supply that companies comply with basic manufacturing standards. FDA takes these obligations very seriously and expects manufacturers to do the same,” Joshua Sharfstein, MD, FDA principal deputy commissioner, said in an agency press release.

According to a Genzyme release, the company will “continue to make significant progress both to improve manufacturing and quality systems in Allston and transfer fill/finish activities to other locations.” Genzyme expects the remediation plan to require about two to three years to complete.

Limiting drug availability

The American Association of Clinical Endocrinologists said in a statement that the legal settlement between the FDA and Genzyme will limit the availability of Thyrogen until the manufacturing conditions have been corrected.

The FDA has agreed to allow the distribution of Thyrogen to patients for whom treatment is deemed “medically necessary.” According to criteria established by the FDA, these include:

l Patients undergoing initial radioiodine ablation of thyroid tissue remnants, post-thyroidectomy, or deemed to be at significantly increased risk for adverse events or complications from undergoing thyroid hormone withdrawal.

l Follow-up testing of patients considered high risk for thyroid cancer recurrence and who have unmeasurable basal thyroglobulin levels and are deemed to be at significantly increased risk for adverse events or complications from undergoing thyroid hormone withdrawal.

Pediatric patients are not generally considered to be within the medically necessary category.

AACE said it will continue to investigate this issue and provide additional information via the Patient Safety Exchange as it becomes available.

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