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

The FDA inspected Toyobo Co. Ltd. in Shiga, Japan, from February 15-25, 2021, identifying significant Current Good Manufacturing Practice (CGMP) violations under 21 CFR parts 210 and 211, rendering their drug products adulterated. The firm failed to thoroughly investigate unexplained discrepancies or failures of batches to meet specifications (21 CFR 211.192). Specifically, they inadequately investigated recurring extrinsic particulate contamination in sterile drug products, failing to determine root causes and implement timely corrective actions. Furthermore, the firm's investigation into reported data integrity breaches was insufficient to determine the full scope of problems. These breaches included operators failing to consistently perform personnel and environmental monitoring, wiping equipment before sampling, misreporting nonviable particle data, and repeating monitoring instead of reporting high values. These issues compromised the sterility assurance of drug products and indicated a systemic failure in data integrity, involving multiple operators. The FDA requires a comprehensive, independent assessment of their investigation system, updated risk assessments for marketed batches, a review of defect limits, and a detailed remediation plan for contamination hazards. The firm must also provide a plan for appropriate aseptic practices, supervisory oversight, and a comprehensive assessment of their Quality Unit's authority and resources. A thorough investigation into data inaccuracies, a risk assessment of their effects on drug quality, and a global CAPA plan are also mandated. The FDA strongly recommends engaging a qualified CGMP consultant. Failure to address these violations may result in import alerts and impact future drug approvals.