FDA 483 - Corden Pharma Boulder, Inc. - May 11, 2012

The FDA inspection revealed significant deficiencies at the facility, many of which were repeat observations from a June 21, 2011 audit. The firm commercially distributed 18 lots of Carboplatin without process validation, and the pH method for Carboplatin finished product and stability testing was unreliable between 2006 and 2011, impacting all distributed lots. Carboplatin lot# (b)(4) failed stability pH testing but was commercially distributed.

The firm failed to submit Field Alert Reports within three working days for numerous out-of-specification (OOS) stability API samples supporting marketed drug products, including Carboplatin, Pentostatin, Sodium Nitroprusside, and Pamidronic Acid. The issue elevation process did not account for unconfirmed stability failures.

Laboratory controls were inadequate; a Pentostatin stability sample OOS for assay was retested, and an outlier result was discarded without proper documentation or SOPs for outlier identification. Cleaning validation for equipment used interchangeably between multiple active pharmaceutical ingredients (Carboplatin, Paclitaxel, Pamidronic Acid, Pentostatin, Sodium Nitroprusside, Tromethamine, Irinotecan, Oxaliplatin) was incomplete. A Paclitaxel API cleaning validation attempt failed due to a manufacturing deviation.

The quality control unit lacked responsibility for approving laboratory procedures; an instrument SOP was changed via email without QC approval, impacting GMP assays for Carboplatin and Oxali