FDA 483 - Alvotech HF - July 04, 2025

Alvotech HF. was subject to an FDA inspection from June 26 to July 4, 2025, at its Reykjavik, Iceland facility, revealing critical observations related to drug substance and drug product manufacturing. Key issues included a failure to establish adequate written procedures for production and process controls, specifically concerning filling equipment that lacked scientific justification for its impact on product quality. The quality unit demonstrated significant deficiencies, such as insufficient evaluation and trending of 159 product complaints, processing drug substance lots into drug products without full quality unit review and release, and a lack of proper oversight for new production runs. Furthermore, a crucial quality agreement with the applicant for drug substance and product manufacturing was not in place.

Contamination control presented a major concern, with inadequate microbial controls in drug substance manufacturing, evidenced by bioburden excursions, fungal recoveries, unrepresentative sampling, and incorrect sample hold time calculations. Environmental controls in classified process areas were also found deficient, marked by consistently elevated microbial contamination rates, repeated detection of mold and fungi, improperly set differential pressure alarms, and an inadequate environmental monitoring process qualification that failed to challenge maximum occupancy conditions. Alvotech HF. is expected to respond to these FDA observations by implementing comprehensive corrective and preventive actions to ensure compliance with regulatory standards.