FDA 483 - Hugel Inc. - August 20, 2021

An FDA inspection of Hugel, Inc., a drug substance and drug product manufacturer in Chuncheon, Gangwon, Korea, was conducted from August 12-20, 2021. The inspection identified several deficiencies.

Observations included inadequate containment of *Clostridium botulinum* spores in drug substance manufacturing areas, posing a cross-contamination risk to drug product areas, with no procedure to prevent personnel movement between these areas. Decontamination of *Clostridium botulinum* spores and toxin was also found to be inadequate, with a spectrometer at risk of contamination and disinfectant qualification studies failing to demonstrate effectiveness against spores and toxin. Environmental monitoring was insufficient as *Clostridium botulinum* spores were not monitored in drug product manufacturing.

Furthermore, an investigation into an out-of-specification (OOS) result for identification and purity (DV19-019) was deemed inadequate, as re-testing was not conducted to confirm the presumed root cause. The SOP for logbook management (AWLS-QA-015:FOS) was not updated promptly after twelve incubator logbooks went missing in 2016 and 2017. A different working cell bank (WCB) lot was used for drug substance manufacturing during the inspection compared to what was submitted, and comparability data were lacking. Finally, a drug product batch failed due to exceeding validated manufacturing time, attributed to delays, damaged vials, and operator breaks (DV2