The issues in Allston are serious and varied—among them:
• “There is a failure to thoroughly review the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed. Specifically . . . Investigations into metal particle contamination in finished drug product concluded equipment used in the aseptic fill process sheds metal particulates into vials before drug product is filled based on the equipment design and intended use.
• “Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use. Specifically, your firm is using vial pans used in the depyrogenation process of drug product vials which you have identified as a source of metal particle contamination in finished drug product because of metal-on-metal contact with the trays and prep components such a metal base, lid, or ring.”
• “Your firm upgraded the refrigeration skid which is used to run the lyophilizer in January 2003. . . . .The Operational Qualification performed on the system did not include functional tests for all critical steps.”
• “The filling line has been in place and in use since 1994. The filling line has not been calibrated for line speed, stopper bowl. speed, or volumetric control. . . . Routine calibration of mechanical and electronic equipment is not performed according to a written program designed to assure proper performance.”
• “The Microbiology Manager confirms there is no document that describes the ‘more rigorous approach’ to qualify operators to participate in sterile operations.”