FDA 483 - Zhejiang Huahai Pharmaceutical Co., Ltd. - January 24, 2025

An FDA inspection conducted from January 16-17 and 20-24, 2025, at Zhejiang Huahai Pharmaceutical Co., Ltd. in Linhai, China, identified significant deficiencies in their drug manufacturing operations. The inspection, documented in an FDA Form 483, revealed multiple observations related to adherence to Good Manufacturing Practices (GMP).

Key issues included ineffective cleaning of non-dedicated equipment, with visible residues of multiple products found on surfaces intended for U.S. market drugs, and cleaning validation studies failing to adequately address hard-to-clean areas. Sterilization process validation for aseptic filling was found to be deficient, particularly concerning smoke studies for critical interventions. The firm also lacked adequate written procedures for production and process controls, impacting visual inspection qualification, tablet compression parameters, and process validation sampling.

Furthermore, the company failed to thoroughly investigate unexplained discrepancies, such as foreign matter in drug batches, out-of-specification dissolution results, out-of-trend impurities, and content uniformity failures. Deficiencies were noted in aseptic processing areas, including the unauthorized use of non-sterile tape to seal a critical gap in a Grade A filling line. Laboratory controls were inadequate, as analytical method validation studies lacked forced degradation for stability testing. Finally, the Quality Control unit's authority was compromised by a lack of audit trail reviews for production equipment and unverified manual data entry. Zhejiang Huahai Pharmaceutical is required to submit a comprehensive response outlining corrective actions to address these serious observations and ensure compliance with regulatory standards.