Genzyme Corporation has provided an update on its progress toward restoring production at its Allston Landing manufacturing facility and in implementing temporary supply management measures. The company recently announced that it had interrupted production of Cerezyme® (imiglucerase for injection) and Fabrazyme® (agalsidase beta) at the plant to sanitize the facility, after identifying a virus in a bioreactor used for Cerezyme production. The virus impairs the viability of cells used in the manufacturing process and is not known to cause infection in humans. Following a collaborative interaction with FDA and EMEA, Genzyme has begun shipping product from finished lots of Cerezyme held in inventory, after PCR testing detected no evidence of Vesivirus 2117. Shipments of Fabrazyme were not put on hold. “We continue to make strong progress toward resolving this situation as quickly as possible, thanks to a broad group of employees across the company who have been working around the clock,” said Henri A. Termeer, Genzyme’s chairman and chief executive officer. “We are confident that the Allston plant will be back online later next month, that we will be able to minimize the impact of constrained supply, and that the measures we are implementing will prevent this issue from occurring again. The support we have received from regulatory authorities, patients, suppliers, and from our industry peers who have shared their experiences and offered expertise and resources, has been heartening.” Because Cerezyme and Fabrazyme inventories are not sufficient to avoid shortages during the period of suspended production and recovery, Genzyme has begun working with regulatory authorities, physicians and patient organizations to carefully manage product supply, with the goal of protecting the most vulnerable patients. The company met this week with the National Gaucher Foundation’s medical advisory board to formulate clinical guidelines for use by U.S. and other physicians during the period of Cerezyme supply constraint. Genzyme will also convene meetings to facilitate the creation of guidelines for managing Fabrazyme supply. In Europe, following the recommendations of the EMEA, Genzyme will issue a letter to health care providers establishing an approach for the use of Cerezyme and Fabrazyme throughout the European Union during the anticipated period of supply constraint. At the Allston plant, Genzyme is following a well-established and proven method for removing viruses, which includes disassembly and removal of equipment, cleaning, disinfection of cell culture and downstream production suites with vaporous hydrogen peroxide, installation of new air filters and insulation, and other measures. The disinfection process has begun, and the company remains on track to complete this work and restore operations in all cell culture suites and downstream processing areas by the end of July. Once the sanitization of the plant has concluded, equipment will be reassembled, tested and brought back into operation, and production will resume on a rolling basis. Genzyme will not have to perform process validation runs in order to resume production. Genzyme continues to evaluate the impact of the interruption in production on the timing and magnitude of constraints on Cerezyme and Fabrazyme supply. The company currently expects the period of constraint for each product to last approximately 6-8 weeks. This period is expected to begin in August for Cerezyme and October for Fabrazyme. Genzyme will provide updated financial guidance reflecting the impact of this situation as soon as possible. Genzyme has now confirmed that the Vesivirus 2117 strain identified at the Allston facility also contaminated production twice in 2008, once at the Allston plant and once at Genzyme’s biologics plant in Belgium. Although Genzyme was not able to detect and identify the virus until this year after it developed a highly specific assay, it took precautionary measures in 2008 and sanitized both facilities at the time. The virus was likely introduced through a raw material used in the manufacturing process, and the company is collaborating with its suppliers to address this issue and implement steps to protect against recurrence. Genzyme is also evaluating adding steps to its raw-materials screening and virus-removal processes to make them more robust, including testing all of its raw materials for the presence of Vesivirus 2117 using the highly specific assay it developed. In addition, Genzyme is collaborating with other biologics manufacturers to learn from their experience and apply this knowledge to resolve the current situation and implement enhanced safeguards. Genzyme intends to share its own experience with this virus through appropriate mechanisms so that others within the industry may benefit. This includes working to ensure that an assay for Vesivirus 2117 becomes widely available to the industry. Genzyme has been operating with lower than usual inventories of Cerezyme and Fabrazyme because it has allocated capacity for Myozyme® (alglucosidase alfa) production at the Allston plant. Myozyme’s worldwide growth has been rapid and strong, and the capacity requirements for the product are substantial because its approved dosage is significantly higher than for similar therapies. Genzyme has been executing a plan to provide additional capacity to support the long-term growth of these three products. Recently, the company received approval in the EU for manufacturing Myozyme at the 4000-liter bioreactor scale at its plant in Belgium. The company is in the process of transitioning all Myozyme production to this plant, which is currently being expanded with the addition of a third 4000-liter bioreactor that is scheduled to come on line in 2011. This will bring Genzyme’s total investment in the plant to nearly $500 million since 2001. In addition, Genzyme is in the late stages of construction on a new plant in Framingham, Massachusetts, for the production of Cerezyme and Fabrazyme. This plant, which will include four 2000-liter bioreactors, will provide substantial additional capacity to support the growth of the two products. Genzyme is investing approximately $300 million to build this facility. It expects to begin qualification runs next year and anticipates regulatory approval for the production of Fabrazyme in 2011 and for the production of Cerezyme in 2012.
