Genzyme (Cambridge, MA) signed a consent decree of permanent injunction that requires the company to correct manufacturing-quality violations at its Allston, Massachusetts, manufacturing facility. Genzyme also will give the federal government $175 million in past profits from the sale of products that were made at the plant.
By signing the consent decree, the company agreed to adhere to a strict timetable to ensure that the Allston plant’s operations fulfill the US Food and Drug Administration’s regulatory requirements. In October 2009, Genzyme submitted a plan to improve quality and compliance at the Allston facility to FDA. The consent decree requires the company to draft a plan to complete the remediation and submit it for FDA approval.
The remediation plan will require specific steps for bringing the Allston plant into compliance within given dates and also will include ongoing oversight from Quantic, Genzyme’s current third-party consultant. If remediation actions are not complete by certain milestones, FDA can require Genzyme to pay $15,000 per day per affected drug until the compliance milestones are met. Genzyme expects that the remediation plan will require approximately two to three years to complete. After the remediation plan has been completed, FDA will require Quantic to oversee Genzyme for five years and to submit annual reports.
The consent decree also requires Genzyme to move all fill–finish operations for its Cerezyme, Fabrazyme, and Thyrogen drugs sold within the United States out of the Allston plant by November 28, 2010. Genzyme also must transfer fill–finish operations for these drugs sold outside of the United States by August 31, 2011. If Genzyme fails to meet these deadlines, FDA can require the company to disgorge 18.5% of revenue for these products.
In November 2009, Genzyme unveiled plans to transfer all fill–finish activities from Allston to other locations. The company now uses excess capacity at its facility in Waterford, Ireland, to fill 80% of its Cerezyme supply. Last week, Genzyme gained regulatory approval to fill and finish Myozyme produced at the 160-L scale at the Waterford facility. The company no longer will conduct fill–finish operations for Myozyme in Allston. Genzyme also has begun the process of transferring remaining filling activities from Allston to an existing Genzyme contract manufacturer.
During an inspection of the Allston plant from Oct. 8, 2009 until Nov.13, 2009, FDA officials found that Genzyme’s systems for ensuring manufacturing quality were inadequate. The inadequate quality systems caused production delays and critical shortages of medically necessary products, and also allowed drugs to be contaminated with metal, fiber, rubber, and glass particles, according to FDA. Officials found that the plant’s manufacturing problems violated FDA’s regulations for good manufacturing practice.
“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,” said Joshua Sharfstein, FDA principal deputy commissioner, in an agency press release
Genzyme also temporarily suspended the production of some products because of a viral contamination in a bioreactor that makes bulk amounts of its drugs. The suspension caused additional drug shortages.
Genzyme is currently shipping Cerezyme at approximately 50% of demand and Fabrazyme at approximately 30% of demand. In June 2010, Genzyme will issue a detailed assessment of the supply of Fabrazyme and Cerezyme. The assessment will consider Fabrazyme working cell-bank performance and the potential effect of the consent decree on product-release times.
“We continue to make significant progress both to improve manufacturing and quality systems in Allston and transfer fill–finish activities to other locations, working as expeditiously as possible through the regulatory pathways globally,” said Henri A. Termeer, Genzyme’s chief executive officer, in a press release
. “We appreciate the guidance the FDA provided over the past year as we work to restore the agency’s confidence in our ability to operate the Allston plant at the highest standards, and return to reliable product supply for patients.” Genzyme has launched a website
that describes additional changes that are intended to strengthen the company for the future.
Genzyme’s Senior Vice-President for Manufacturing Sciences and Technical Operations W. Blair Okita, Genzyme’s Senior Vice-President for Global Product Quality Ronald Branning, and Termeer agreed to the decree. The document was filed on Monday in the US District Court for the District of Massachusetts and requires court approval. FDA is collaborating with Genzyme during the company’s remediation to ensure that the company’s medically necessary drugs remain available.