Genzyme's vicious virus
One of the most highly visible of the recent GMP snafus involved Genzyme and the discovery of Vesivirus 2117 in a bioreactor at its Allston Landing facility outside Boston. The contamination led to a plant shutdown and extended cleanup. A subsequent shortage of one of the drugs made there led first to a rationing of supplies and then to the FDA asking a Genzyme competitor to offer its experimental treatment under an expanded access program.
Although the biggest problems--and the biggest press coverage--occurred in the spring and summer of 2009 and beyond (our coverage starts here), early indications showed during a fall 2008 inspection that resulted in warning letter NWE-08-09W of February 2009.
The biotech giant was cited for failure to establish and follow written procedures to prevent microbiological contamination of sterile drug products. Air flow patterns were part of the problem, as were "significant deviations" in the manufacture of bulk drug substances and drug components. "Your firm does not conduct adequate monitoring of bioburden after hold times of intermediates or pooled buffers during purification of Fabrazyme, Myozyme, and Cerezyme," according to the warning letter. In addition, pooled buffers used in purification steps are not adequately controlled for composition. "Processes for formulating pooled buffers do not assure that the pooled buffers will meet their specifications, the letter states.
Another finding concerned equipment maintenance. For example, inspectors found that internal surfaces and manual valves on the stainless steel chromatography columns used during drug substance purification were not adequately maintained. Maintenance was never been performed on the interior of columns to prevent adverse impact on cell cultures due to metal contamination. Visible rouging was observed on the exterior of the chromatography skid (b)(4) used in purification of Myozyme.
The FDA also expressed concern about the company's failure to maintain computer systems in a validated state. The letter cites a system used to formulate the elution buffer for Fabrazyme that hadn't been updated since 1999, as well as the continued operation of an aseptic fill line whose speed hasn't been validated.