ARL Biopharma, Inc. – FDA 483, Nov 8, 2012

During an inspection conducted from October 12 to November 8, 2012, the FDA issued a Form 483 to ARL Biopharma, Inc. dba Analytical Research Laboratories. The inspection revealed significant observations regarding the firm's quality control practices, particularly in endotoxin testing for human drug products.A primary issue identified was the firm's failure to fully adhere to all parts of the United States Pharmacopeia General Chapter <85> Bacterial Endotoxins Test. Specifically, the Maximum Valid Dilution (MVD) was not consistently calculated according to the USP <85> formula. The firm did not ensure clients provided the necessary dosing information for drug products, which is crucial for establishing accurate endotoxin limits. Examples cited included injectable drug products from clients like NECC and Ameridose, where endotoxin limits were not established due to this oversight.Furthermore, the inspection uncovered a critical lack of investigation into 13 confirmed endotoxin failures that occurred between October 2010 and October 2012. There was no documentation of any investigations conducted for these failures, including a specific instance for Sodium Bicarbonate submitted by NECC. The firm's existing Microbiology Out-of-Specification Investigation standard operating procedure also did not address endotoxin testing failures.To address these findings, ARL Biopharma is expected to fully implement USP <85> guidelines for endotoxin testing, ensure proper MVD calculation with client dosing information, establish endotoxin limits, and thoroughly investigate and document all endotoxin failures. The firm also needs to revise its standard operating procedures to cover endotoxin testing out-of-specification results.