FDA 483 - Horizon Pharmaceuticals, Inc. - February 16, 2024

During an inspection conducted from February 5 to 16, 2024, Horizon Pharmaceuticals, Inc., a sterile drug manufacturer, received an FDA Form 483 detailing significant observations regarding deviations from current Good Manufacturing Practices (cGMP). The primary concerns involved deficiencies in the company's Quality System, Laboratory System, Complaint Records, and Facilities and Equipment.

Key issues included a lack of authority within the Quality Control Unit (QCU) to fully investigate environmental monitoring out-of-specification (OOS) results, leading to the release of potentially contaminated batches of Arformoterol Tartrate inhalation solution without appropriate corrective actions. Investigations were found to be incomplete and inaccurate, failing to consistently identify organism sources. The QCU demonstrated inadequate oversight in areas such as vendor qualification, product testing, and annual product reviews, often releasing product conditionally or with conflicting quality agreements.

Further observations highlighted incomplete and incorrect complaint records, a failure to thoroughly qualify contract laboratories, and deficiencies in batch record completeness, drug product sampling methodologies, and review of laboratory logbooks. Active Pharmaceutical Ingredients were utilized past their retest dates without proper reevaluation. Facility issues encompassed inadequate ISO classification room designs, improper storage of rejected materials outdoors, and insufficient smoke studies to assure aseptic conditions.

These observations require Horizon Pharmaceuticals to implement robust corrective and preventive actions, including strengthening QCU authority, improving investigation processes, ensuring data integrity, updating procedures, properly qualifying vendors, and upgrading facility controls to assure product quality and patient safety.