FDA Warns Pharmathen Over Sterility, Data Integrity Concerns

FDA has issued a Warning Letter to Greek contract manufacturer Pharmathen International citing significant GMP violations at its sterile drug manufacturing facility in Sapes, Greece, including deficiencies in aseptic processing, contamination control, quality investigations, facility design, and data integrity.

The just-posted 5/27 letter follows an FDA inspection conducted 11/2025 at the company's Rodopi Prefecture facility. FDA concluded that the firm's methods, facilities, and controls for manufacturing sterile pharmaceutical products did not comply with GMP requirements, rendering its products adulterated under the Federal Food, Drug, and Cosmetic Act.

The agency said the inspection uncovered systemic failures affecting sterile manufacturing operations used to produce injectable products for the U.S. market. Among the most serious observations, FDA cited inadequate airflow control in Pharmathen's aseptic filling operations. Smoke studies conducted on a restricted access barrier system used to fill sterile powder drug products failed to demonstrate unidirectional airflow, a fundamental requirement for protecting exposed sterile products from contamination.

FDA noted repeated detection of gram-negative microorganisms in ISO 5 aseptic processing environments. The agency emphasized that such contamination is highly atypical in sterile manufacturing areas and criticized the firm's investigations into these events as inadequate.

Regarding deficient quality investigations, FDA said Pharmathen repeatedly failed to conduct thorough investigations into sterility failures, environmental monitoring excursions, out-of-specification results, and media-fill failures.

According to the letter, recurring contamination events and aseptic process failures over a five-year period were frequently attributed to operator error without adequate root-cause analysis or implementation of effective corrective and preventive actions. FDA stated that the firm's proposed corrective actions lacked sufficient detail to demonstrate how future contamination risks would be prevented.

The agency further found that Pharmathen lacked a compliant facility monitoring system capable of recording and retaining critical environmental data such as pressure differentials, temperature, humidity, and alarm events. Monitoring equipment reportedly displayed only real-time readings and did not maintain historical records. FDA said the deficiencies prevented the company from detecting and investigating environmental excursions that could compromise sterility assurance.

Additionally, the FDA letter raised broader concerns regarding data integrity and laboratory controls. FDA investigators found that microbiological samples, including sterility, environmental monitoring, and water testing plates, lacked adequate documentation and traceability. Critical information regarding sample preparation and identification was missing, and records were not consistently created contemporaneously. The agency also questioned controls surrounding laboratory documentation generated through computerized systems.

FDA noted that Pharmathen voluntarily suspended production of all products intended for the U.S. market in 11/2025. It said the company subsequently agreed to halt manufacturing and distribution of U.S.-bound products until corrective actions are completed and evaluated by an external consultant.

FDA also advised the company to consider removing certain injectable and suspension products from the U.S. market due to concerns regarding sterility assurance. Following discussions with the agency, sponsors of affected products subsequently initiated voluntary recalls.

FDA’s letter requested extensive remediation measures, including independent assessments of aseptic processing operations, contamination controls, quality systems, laboratory practices, and data integrity systems. The agency also recommended that Pharmathen retain a qualified GMP consultant to conduct a comprehensive audit before seeking to resume manufacturing products for the U.S. market.