Pharmathen International S.A. — FDA Warning Letter Findings

Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas (21 CFR 211.42(c)(10)). Your aseptic processing operation was inadequately designed to prevent contamination of your sterile (b)(4) drug products. Significantly, your room pressurization and facility monitoring systems were fundamentally flawed…

Your firm failed to follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)). The airflow visualization studies (i.e., smoke studies) you performed for the (b)(4) aseptic vial filling line you use to fill sterile powder drug products for the U.S. market did not demonstrate unidirectional airflow. This…

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192). Your firm did not adequately investigate out-of-specification (OOS) and out-of-limit (OOL) results. Your investigations of sterility failures and significant environmental monitoring excursions lacked adequate scientific rationale to support root causes…

Your firm failed to document at the time of performance required laboratory control mechanisms and to record and justify any deviations from required laboratory control mechanisms (21 CFR 211.160(a)). Your control over microbiological laboratory records was inadequate. Our investigators found that microbial plates (for sterility, environmental monitoring, and water samples) in incubators lacked appropriate documentation. For example, you did not have raw data and information…