FDA WARNING_LETTER - Sandoz Inc. - March 31, 2008

The FDA issued a Warning Letter to Sandoz following a March 2008 inspection of their Wilson, NC facility, revealing significant Current Good Manufacturing Practice (CGMP) deviations in the manufacturing of drug products, including Metoprolol Succinate ER tablets, rendering them adulterated. Key violations cited include the failure to establish and follow written procedures for process control, specifically inadequate validation of the Metoprolol manufacturing process (21 CFR § 211.100(a)). The firm also failed to thoroughly investigate unexplained discrepancies or batch failures (21 CFR § 211.192), with numerous investigations delayed or incomplete. Further deficiencies involved not including in-process and laboratory control results in batch records (21 CFR § 211.188(b)(5)), incomplete master production and control records (21 CFR § 211.186(b)(9)), and inadequate laboratory controls for specifications (21 CFR § 211.160(b)), including the release of non-conforming lots. Critical data integrity issues were identified, with computer systems lacking controls to prevent modification or deletion of raw data and no audit trails (21 CFR § 211.68(b)). The Quality Control Unit (QCU) was found to have failed in its responsibilities, including ensuring investigations and process validation (21 CFR § 211.22(d)). The FDA expressed concerns about the continued distribution of Metoprolol and the lack of a global approach to quality. Sandoz must provide a written response within 15 working days detailing corrective actions and their prevention of recurrence, with potential regulatory actions including disapproval of applications if deficiencies are not corrected.