FDA EIR - Hugel Inc. - March 10, 2023

An FDA inspection of Hugel Inc. (Site 2) in Chuncheon-si, Republic of Korea, was conducted from February 27 to March 10, 2023. The inspection assessed the manufacturing operations for Botulinum Neurotoxin A drug substance and drug product, supporting Biologics License Application 761225, and was carried out under Good Manufacturing Practices (GMP) and relevant guidance documents. The inspection resulted in a Form FDA 483 listing five significant observations. Key issues included the firm's lack of an established cleaning and disinfection program to prevent microbial contamination, particularly Clostridium botulinum spores and toxin, in controlled manufacturing areas. Laboratory records were found deficient, lacking adequate controls for assay data traceability, reliability, and accuracy. Procedures designed to prevent microbiological contamination of sterile drug products were neither fully established nor consistently followed, with concerns raised about aseptic setup operations and environmental monitoring. The environmental monitoring program for the drug substance facility was deficient, as it did not specifically monitor for Clostridium botulinum. Finally, the quality unit’s oversight of GMP manufacturing operations was deemed inadequate, evidenced by unvalidated electronic data acquisition systems, incomplete process equipment cleaning validation, and absence of validated sample shipping conditions to contract laboratories. Hugel Inc. committed to providing a written response to these observations within 15 business days.