FDA 483 - Hugel Inc. - March 10, 2023

During an FDA inspection from February 27, 2023, to March 10, 2023, Hugel, Inc. (Site 2) in Chuncheon-si, Gangwon-do, Republic of Korea, a drug substance and drug product manufacturer, received a Form 483 with five observations.

**Observation 1** details deficiencies in the cleaning and disinfection program, specifically lacking studies to demonstrate the effectiveness of agents against Botulinum Neurotoxin A (BoNT/A) residue and Clostridium botulinum on all manufacturing surfaces. The disinfectant efficacy studies were inadequate, failing to include all representative materials of contact and sufficient evidence of spore log reduction. Sporicidal agents were not sufficiently used in Grade C and D areas, and cleaning procedures lacked documentation and verification of surface wetness for validated contact times.

**Observation 2** highlights inadequate laboratory record controls, leading to issues with assay data traceability, reliability, and accuracy. This included the use of uncontrolled forms for raw data, insufficient contemporaneous verification during potency assays, lack of traceable evidence for animal observations, and no reconciliation of animals at disposal for potency assays. For the Neurotoxin content ELISA assay, plate layouts were not documented, and there was no contemporaneous verification of sample addition.

**Observation 3** addresses failures in procedures to prevent microbiological contamination of sterile drug products. During aseptic filling operations, operators extended hands over sterile components, violated first air principles, and touched