2. Failure to adequately investigate out-of-specification results and implement appropriate corrective actions.
You invalidated an out-of-specification (OOS) related substances test result for API [redacted] batch [redacted], listed in a pending drug application, without scientific justification.
In your response, you stated that you performed an investigational hypothesis study to evaluate the effect of sonication on API [redacted] batch [redacted]. You concluded that [redacted] generated an unknown impurity at the same relative retention time (RRT) and similar percentage peak area as the OOS result.
Your response is inadequate because you did not adequately investigate all potential causes of the unknown impurity. You attributed the OOS result to degradation caused by [redacted], a sample preparation step performed during your test procedure. You also did not provide adequate scientific justification for your OOS result root cause. We note that three other batches of API [redacted] followed this [redacted] preparation and analysis procedure during the same sequence with no OOS results for these [redacted] batches.