FDA 483 - Toyobo Co. Ltd. - February 25, 2021

The FDA Form 483 details multiple deficiencies at a pharmaceutical manufacturing facility. The facility failed to thoroughly review unexplained discrepancies, including black particles and deformed stoppers in finished drug product vials, without proper microscopic examination of components or assessment of stopper integrity post-sterilization.

Environmental monitoring in aseptic processing areas (Grade A/B/C) was deficient, with gaps in continuous measurement, recording, and trending from 2018-2021. Falsified non-viable particulate counts were reported, misattributing Grade A data to a Grade B area.

Production personnel exhibited poor sanitation and health habits, including squatting, sitting, rapid movement in Grade B areas, and infrequent gloved hand disinfection, inconsistent with SOPs.

Laboratory records lacked complete data, with original test results not analyzed and no OOS investigations initiated. A planned deviation (TC002) allowed raw material use before related substance release testing, with multiple analyses performed without adequate explanation for not reporting original results.

Visual inspection procedures (SOP V002) for aseptically filled vials were not followed, lacking documented vision exams by qualified professionals. Self-testing and co-worker verification were permitted, with no documented second verifiers. Vision tests were performed beyond the required frequency.

CAPAs for data integrity deficiencies in environmental monitoring were not comprehensive, failing to address root causes identified in prior QC testing issues from 2017-2018. A temporary