Signa SA de CV – FDA Warning Letter, Dec 20, 2019

The FDA issued a Warning Letter to Signa S.A. de C.V. following an inspection from December 16-20, 2019, at their Toluca, Mexico facility, identifying significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API), rendering their API adulterated.

Key violations include the failure to adequately investigate out-of-specification (OOS) results and implement appropriate corrective actions. Specifically, an OOS result for related substances in a process validation batch from January 2018 was inadequately investigated, with an unsupported root cause identified and insufficient corrective actions. This batch's failing data was intended for process validation, and at least one finished API batch from these studies was released to the U.S. market. Another OOS assay result from October 2018 was invalidated based on retest results and an unsubstantiated root cause (analytical balance instability due to multiple analysts), without a thorough manufacturing investigation.

The FDA requires a comprehensive, independent assessment and remediation plan for their deviation investigation and CAPA programs, including improvements in competencies, root cause evaluation, CAPA effectiveness, and quality assurance oversight. A retrospective, independent review of all invalidated OOS results for U.S. products since January 2017 is also required, along with a detailed report. The letter notes similar CGMP deviations at other company facilities, indicating inadequate management oversight.

Failure to correct these deviations