Abraxis cited for problems with labeling, aseptic conditions.

Abraxis Pharmaceutical Products, Melrose Park, IL, Chicago District

Investigators Carrie Ann Plucinski and Russell Riley gave Abraxis a three-item 483 after an inspection of the drug manufacturer Aug. 23-Sept. 28, 2007.

The inspectors found that Abraxis approved and released for use labeling and packaging materials that did not meet written specifications. The firm labeled one lot of Octreotide Acetate Injection with vial labels that incorrectly stated the concentration of the drug as 0.05 mg/mL rather than 0.5 mg/mL. The company had recently changed its labels to add its new name and "LOT/EXP"; the concentration on the labels was inadvertently changed during this process, the investigators concluded.

The label was double-proofed by two members of the firm's Regulatory Affairs labeling department according to the company's SOP "Labeling Review and Approval." However, the employees failed to notice the change in concentration and approved the label. The failure to recognize the inadvertent change in the drug concentration on the new vial labels allowed the release and distribution of this lot of Octreotide Acetate Injection, which Abraxis recalled on 8/2/07.

The firm had documentation to show that only one of the two employees who inspected the label proof was trained on the labeling SOP at the time of the incident. The untrained employee was a temporary employee with responsibility to review and approve labeling.

The inspection also revealed that the system for cleaning and disinfecting the room and equipment to produce aseptic conditions was deficient. "The firm's current cleaning regimen has not been validated for efficacy on methlymethacrylate surfaces," the investigators wrote in the 483.

The company's SOP "Disinfection of the Aseptic Processing Areas" did not adequately describe the methods for cleaning aseptic processing areas nor the sequence of wipe-downs of the filling equipment, the 483 noted.

Further, the disinfection record that documented the cleaning, as required by the SOP, was not clear about reasons that remedial action cleaning was done, nor about the areas that were cleaned with each disinfectant. Currently, the locations are listed on the Disinfection Record and are initialed and dated when the cleaning is performed. "There is no way of knowing, for example, when the requirement to clean the curtains surrounding the Class 100 area of the filling rooms is met," Plucinski and Riley wrote.

The Room Use and Activity Log used to document activities such as cleaning and filling for each room was not clear about the types of cleaning being performed. "For example, it is not clear when the weekly and monthly cleaning is being performed versus daily cleaning," the report stated.

The system for monitoring environmental conditions in aseptic processing areas was deficient, the investigators found. They noted that Abraxis failed to perform all of the required anaerobic environmental monitoring during two media fill lots. These fills were performed under anaerobic conditions in response to a sterility-positive investigation for Abraxane, in which the organism was identified as Propionibacterium acnes, a microaerophilic organism that grows well under anaerobic conditions.

The company's SOP "Media Fill Qualification of the Aseptic Filling Process" requires that anaerobic airborne environmental monitoring be performed, alternating with each aerobic viable air sample taken at intervals.

It also requires that both anaerobic and aerobic audit surface and critical surface site monitoring be performed at the end of the fill. A media fill of Fluid Thioglycollate (FTG) on Feb. 8, 2007, was performed under anaerobic conditions, but Abraxis did not perform the end-of-fill critical surface site monitoring under anaerobic conditions.

A media fill of Tryptic Soy Broth(TSB) on Aug. 1, 2007, was also done under anaerobic conditions. The firm failed to perform anaerobic viable airborne environmental monitoring or anaerobic audit surface and critical surface site monitoring for this lot, the 483 stated. Two positive vials were found, resulting in a failing media fill. The organisms identified were Staphylococcus epidermidis and Alternaria alternata, a mold.

"All sublots passed aerobic growth promotion; however, two sublots did not pass anaerobic growth promotion," the investigators wrote. "The failure of the anaerobic growth promotion test and the missed anaerobic environmental monitoring indicate that anaerobic contamination during the media fill most likely would not have been discovered."

Abraxis Pharmaceutical Products, 8/23-9/28/07, Doc. 110078 $2 plus retrieval