Receipt of the warning letter marks another twist in Genzyme’s attempt to scale up production of its treatment for Pompe disease, with the difficulties now stretching back 11 months.
In this latest development the US Food and Drug Administration (FDA) found current good manufacturing practice (cGMP) deficiencies at Genzyme’s facility in Allston, Massachusetts.
These could affect “the identity, strength, quality and purity” of drugs manufactured at the site, which also produces Fabrazyme and Cerezyme. This alleged quality control issue is the result of inadequate “monitoring of bioburden after hold times of intermediates or pooled buffers during purification”.
In addition the agency found that the procedural and automated in-process controls used in formulating the pooled buffers were not sufficient to ensure their composition.
These issues were compounded by the failure to establish and follow written procedures designed to prevent microbiological contamination in sterile production areas.
In particular the investigator noted that five operations and practices, including critical aseptic connections and active viable air sampling, were not performed during air flow pattern testing studies. Further deficiencies were found in the maintenance of equipment and computer systems.
Genzyme issued two responses to the FDA’s initial form 483 but these were insufficient for the agency to adequately evaluate the biotech’s corrective actions. Consequently the FDA issued Genzyme with a warning letter, which identifies seven areas where more detail is needed.
Allston’s issues mount
Genzyme setup its Allston facility to produce Myozyme in 2000L reactors but the FDA deemed that in scaling up from 160L the therapeutic changed sufficiently to make it a different product.
Consequently Genzyme filed a new Biologics Licence Application (BLA) for the 2000L version and called the product Lumizyme, which would result in two versions of the same treatment being marketed under different names.
However, Genzyme suffered a further setback when the FDA called for more information just as the biotech thought it was nearing approval, putting the process back six months and cutting sales forecasts by $65m (€51m)..