Out-of-Specification (OOS) Investigation Checklist (FDA 2006 Guidance)

Initial Notification and Triage

Capture and escalate the result promptly.

• Was the OOS result reported to the supervisor promptly and documented on the day of occurrence? *
• Record the test, specification, and the failing result value. *
• Is the original data preserved without alteration or deletion? *
• Was the sample and preparation secured and retained pending investigation? *

Phase I Laboratory Investigation

• Did the analyst and supervisor conduct an assessment of the accuracy of the result before any retesting? *
• Were instruments, standards, calculations, and system suitability reviewed for assignable laboratory error? *
• Is a clearly documented laboratory root cause identified before invalidating the original result? *
• Was the original result invalidated only with a scientifically justified, documented assignable cause? *

Retesting and Resampling

• Is retesting performed under a pre-approved protocol defining who, how many, and criteria before testing begins? *
• Is resampling justified and performed only when the original sample is compromised or insufficient? *
• Is outlier testing applied only where the method specifies it and never to biological assays inappropriately? *
• Are all original and retest data reported, retained, and not discarded? *

Phase II Full-Scale Investigation

• If no laboratory cause is confirmed, was a full-scale manufacturing investigation initiated? *
• Does the investigation review the batch record, process, and other batches potentially affected? *
• Is the scope extended to other lots and products associated with the identified cause? *
• Is the investigation completed within the established timeframe (typically 30 days) or an extension justified? *

Conclusion and Disposition

• Is a documented conclusion reached that is supported by the weight of the data? *
• Is the batch disposition (release, reject, or reprocess) approved by the quality unit? *
• Are CAPAs defined to prevent recurrence where a cause was identified? *
• Quality unit sign-off on the OOS investigation. *