Genzyme’s consent decree for GMP violations at its Allston, Massachusetts plant will require it to pay a $175 million “disgorgement fee” and bring the plant back into compliance with applicable regulations within a specified time frame, during which time shortages of several of its drugs will continue. The consent decree was filed in the U.S. District Court for the District of Massachusetts on May 24, 2010, and is subject to court approval.
Issues at the Allston plant surfaced in October 2008, when an FDA inspection led to issuance of an FDA form 483, followed by a Warning Letter in February 2009.
The letter delineated issues involving both drug products (Fabrazyme, Cerezyme and Myozyme) and bulk substances and components. The drug product discussion focused on the firm’s microbiological contamination control procedures – in particular its air flow studies.
At issue in the bulk substance area was bioburden monitoring after hold times of intermediates or pooled buffers during purification of Fabrazyme, Myozyme and Cerezyme. The letter also maintains that Genzyme’s current procedural and automated in-process controls for formulating pooled buffers did not assure that the pooled buffers would meet their specifications. FDA asserted that the firm’s follow up to these “documented deviations did not include training of operators or those supervising formulation operations.” Genzyme’s maintenance of certain bulk process equipment and computer systems in a validated state was also cited. (IPQ, May/June 2009)
The plant’s problems expanded in June 2009 when a virus that impairs cell growth was detected in one of six bioreactors. Genzyme decided to interrupt bulk production at the plant for six weeks to sanitize the facility, leading to shortages of the drugs produced there.
At a follow-up inspection at the Allston plant last Fall, FDA continued to find significant problems in the firm’s systems and issued a 49-item 483.
FDA National Expert Investigator Thomas Arista and his team identified a broad range of deficiencies during the November 2009 inspection. Foremost among these was a concern with Standard Operating Procedures (SOPs) regarding deviations. The team found, “no established standard operating procedure to describe the periodic review and the contents of the review of deviations and investigations performed by the Quality Unit.”
(Further analysis of Genzyme’s November 483 and May consent decree and links to the 483, warning letter, consent decree and other related documents are provided in the full story available to subscribers on page 2).
[Editor’s Note: The June issue of IPQ will provide an in-depth report on the changing inspection and GMP enforcement landscape in the US, EU, and globally.]
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