FDA WARNING_LETTER - Actavis Laboratories FL, Inc. - July 19, 2018

The FDA inspected Actavis Laboratories FL, Inc. from July 9 to 19, 2018, identifying significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals (21 CFR parts 210 and 211), rendering their drug products adulterated under section 501(a)(2)(B) of the FD&C Act. The firm failed to establish adequate written procedures for production and process control (21 CFR 211.100(a)), particularly for laser-drilled tablet manufacturing, which lacked sufficient design, validation of critical parameters, and evaluation of visual inspection system changes. Additionally, Actavis failed to establish control procedures to monitor output and validate manufacturing processes (21 CFR 211.110(a)), including inadequate operator qualification for in-process checks and AQL inspections, and insufficient procedures, lighting, and equipment. The Quality Control Unit was deemed inadequate (21 CFR 211.22(a)), failing to provide robust oversight of the laser drilling process, validation, change management, equipment maintenance, training, and timely investigations, leading to voluntary recalls. Finally, the firm failed to thoroughly investigate unexplained discrepancies or batch failures (21 CFR 211.192), exhibiting inadequate root cause analyses and ineffective corrective and preventive actions for drug product defects. These are repeat observations, indicating inadequate executive management oversight. Actavis must promptly correct all violations, respond within 15 working days, and address potential drug supply disruptions. Failure to comply may result in legal action, withholding of drug application approvals, and refusal of export certificates.