Last year was a difficult one in the biotech-manufacturing arena. The H1N1 vaccine shortage in October and November brought
home the perils of influenza vaccine development and production, especially when working with new viral strains each year.
A leading biotech manufacturer suffered major losses caused by serious problems on the production and compliance front. Despite
several decades of experience in monitoring bioreactors and refining cell culture operations, the production of safe, pure,
and potent biologics remains a tricky business.
DEBACLE AT GENZYME
The troubles at Genzyme began two years ago when it sought to scale up production of its new treatment for Pompe disease,
Myozyme (alglucosidase), at its flagship Allston Landing facility in Massachusetts. With six large bioreactors, that plant
produces Genzyme's lead product, Gaucher disease treatment Cerezyme (imiglucerase), along with Fabrazyme (agalsidase) for
Fabry disease. Unfortunately, initial commercial batches of Myozyme made at Allston Landing differed from those made at Genzyme's
smaller Framingham facility, requiring the company to conduct additional clinical trials and submit a new license application
for the product.
In addition, an inspection of the Allston Landing plant by the US Food and Drug Administration in the fall of 2008, found
deviations from good manufacturing practices (GMPs), including inadequate procedures for preventing contamination, equipment
maintenance, maintaining in-process controls, and for computer systems validation. Genzyme thought it had addressed all these
deficiencies by February 2009, but an FDA warning letter requested additional actions and information, as did another FDA
communiqué in May.
As Genzyme struggled to address the FDA's concerns, in June 2009 it discovered viral contamination of a bioreactor used to
produce Cerezyme in-process material. The company had to close the Allston Landing facility altogether for several weeks for
decontamination. Almost all of the starting material used to make Cerezyme was scrapped, and several thousand patients were
left with limited access to therapy for these very serious conditions.
As the cleaning process concluded, Genzyme then discovered problems with its fill–finish process at Allston; evidence of metal
particulates, fibers, and other minute particles in certain batches of Cerezyme and Fabrazyme prompted a shutdown of those
operations. Genzyme transferred those activities to facilities in Waterford, Ireland, and Geel, Belgium, along with all large-scale
bulk production for Myozyme. Genzyme also contracted with Hospira to perform fill–finish work for its major drugs to support
what it hoped would be expanded production in the coming year. The company is anxious to ramp up output because the FDA has
moved to alleviate the Cerezyme shortage by fast-track approval of alternative therapies made by UK-based Shire and by the
Israeli firm Protalix Biotherapeutics, which has linked up with Pfizer to commercialize its Gaucher treatment.
By the end of 2009, Genzyme was beginning to ship new lots of Cerezyme and Fabrazyme. But by then, revenues had slumped, along
with the company's standing with investors. New competition was on the horizon, and the company had to implement a two-year
corrective action plan to address the FDA's concerns about manufacturing processes and controls. Prominent stockholders raised
questions about the leadership of Genzyme CEO Henri Termeer, who moved to deflect these challenges by bringing in new senior
executives to oversee manufacturing, operations, and regulatory affairs. It remains to be seen if these responses are too
little, too late.