Investigation of out-of-specification (OOS) results during content uniformity validation: identification of acid-induced degradation caused by CIP residues

Out-of-specification (OOS) results represent critical deviations within pharmaceutical quality systems, requiring systematic and scientifically justified investigation to determine their origin (FDA, 2006). Such deviations may arise from analytical errors, process variability, or chemical instability of the active pharmaceutical ingredient (API). Despite well-established regulatory frameworks for OOS investigations, real-case studies demonstrating direct chemical causes remain limited. Therefore, the objective of this study was to investigate the root cause of OOS results observed during validation of the content uniformity test and to evaluate potential degradation mechanisms of the active substance.